2024 |
Meakin AS, Nathanielsz PW, Li C, Clifton VL, Wiese MD, Morrison JL, 'Maternal obesity impacts fetal liver androgen signalling in a sex-specific manner', Life Sciences, 337 (2024) [C1]
Background: Maternal obesity (MO) increases fetal androgen concentrations, the prevalence of macrosomia, and predisposes offspring to metabolic dysfunction in later life, especial... [more]
Background: Maternal obesity (MO) increases fetal androgen concentrations, the prevalence of macrosomia, and predisposes offspring to metabolic dysfunction in later life, especially males. These risks may be, in part, the result of increased liver-specific androgen signalling pathway activity in utero. Androgen signalling activity can be suppressed by androgen metabolism via cytochrome P450 (CYP) isoenzymes (CYP2B6, CYP3A) or through inhibition of the full-length androgen receptor (AR-FL) via the antagonistic isoform, AR-45. We hypothesised MO impairs CYP enzyme activity and AR-45 expression in male fetal livers, thereby enhancing activity of androgen signalling pathways. Methods: Nine months prior to pregnancy, nulliparous female baboons were assigned to either ad libitum control or high fat diet. At 165 day (d) gestation (term, 180 d) fetal liver was collected (n = 6/sex/group). CYP activity was quantified using functional assays; subcellular AR expression was measured using Western blot. Results: CYP2B6 and CYP3A activity, and nuclear expression of AR-45, was reduced in MO males only. Nuclear AR-45 expression was inversely related with fetal body weight of MO males only. Conclusions: Reduced CYP2B6 and CYP3A activity in conjunction with decreased nuclear AR-45 expression may enhance liver androgen signalling in males from MO pregnancies, thereby increasing the risk of macrosomia, as well as metabolic dysfunction in later life.
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2024 |
Robinson JL, Gatford KL, Clifton VL, Morrison JL, Stark MJ, 'The impact of maternal asthma on the fetal lung: Outcomes, mechanisms and interventions', Paediatric Respiratory Reviews, (2024) [C1]
Maternal asthma affects up to 17% of pregnancies and is associated with adverse infant, childhood, and adult respiratory outcomes, including increased risks of neonatal respirator... [more]
Maternal asthma affects up to 17% of pregnancies and is associated with adverse infant, childhood, and adult respiratory outcomes, including increased risks of neonatal respiratory distress syndrome, childhood wheeze and asthma. In addition to genetics, these poor outcomes are likely due to the mediating influence of maternal asthma on the in-utero environment, altering fetal lung and immune development and predisposing the offspring to later lung disease. Maternal asthma may impair glucocorticoid signalling in the fetus, a process critical for lung maturation, and increase fetal exposure to proinflammatory cytokines. Therefore, interventions to control maternal asthma, increase glucocorticoid signalling in the fetal lung, or Vitamin A, C, and D supplementation to improve alveologenesis and surfactant production may be beneficial for later lung function. This review highlights potential mechanisms underlying maternal asthma and offspring respiratory morbidities and describes how pregnancy interventions can promote optimal fetal lung development in babies of asthmatic mothers.
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2024 |
Hofstee P, Lum JS, Chow YY, Wittwer MR, Arstall M, Dekker G, et al., 'Urine congophilia associated with preeclampsia does not persist 6-months postpartum', Placenta, 147 52-58 (2024) [C1]
Introduction: Preeclampsia is a common hypertensive disorder of pregnancy. Several studies have demonstrated that protein aggregates, detected through urine congophilia, is associ... [more]
Introduction: Preeclampsia is a common hypertensive disorder of pregnancy. Several studies have demonstrated that protein aggregates, detected through urine congophilia, is associated with preeclampsia; however, it has yet to be investigated whether urine congophilia remains postpartum in these women. In this study, we aimed to augment prior studies and determine whether urine congophilia is present postpartum. Methods: Women were recruited from Lyell McEwin Hospital, South Australia. Urine samples were collected during pregnancy and 6-months postpartum from women with non-preeclampsia pregnancies (n = 48) and women with pregnancies complicated by preeclampsia (n = 42). A Congo Red Dot blot test, total protein and creatinine levels from urine, as well as serum Soluble fms-like tyrosine kinase 1 to placental growth factor ratio (sFlt-1:PlGF), were assessed and correlated. Results: Preeclamptic women exhibited increased urine congophilia (P < 0.01), sFlt-1:PlGF ratio (P < 0.0001) and total protein (P < 0.01) during pregnancy; with a positive correlation between urine congophilia and total protein across the entire cohort (P < 0.0001). Although urine congophilia was no longer detected 6-months postpartum in preeclamptic women, total protein remained elevated (P < 0.05). sFlt-1:PlGF ratio during pregnancy was positively correlated with congophilia across the cohort (P = 0.0007). Serum creatinine was also higher in preeclamptic women during pregnancy (P < 0.001). Discussion: These results support that urine congophilia is significantly elevated in pregnancies complicated with preeclampsia and show that it does not continue postpartum, although larger cohort studies are needed to determine its feasibility as a diagnostic marker.
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2024 |
Meakin AS, Smith M, Morrison JL, Roberts CT, Lappas M, Ellery SJ, et al., 'Placenta-Specific Transcripts Containing Androgen Response Elements Are Altered In Silico by Male Growth Outcomes', International Journal of Molecular Sciences, 25 (2024) [C1]
A birthweight centile (BWC) below the 25th is associated with an elevated risk of adverse perinatal outcomes, particularly among males. This male vulnerability may stem from alter... [more]
A birthweight centile (BWC) below the 25th is associated with an elevated risk of adverse perinatal outcomes, particularly among males. This male vulnerability may stem from alterations in placenta-specific androgen signalling, a signalling axis that involves the androgen receptor (AR)-mediated regulation of target genes containing androgen response elements (AREs). In this study, we examined global and ARE-specific transcriptomic signatures in term male placentae (=37 weeks of gestation) across BWC subcategories (<10th, 10th¿30th, >30th) using RNA-seq and gene set enrichment analysis. ARE-containing transcripts in placentae with BWCs below the 10th percentile were upregulated compared to those in the 10th¿30th and >30th percentiles, which coincided with the enrichment of gene sets related to hypoxia and the suppression of gene sets associated with mitochondrial function. In the absence of ARE-containing transcripts in silico, <10th and 10th¿30th BWC subcategory placentae upregulated gene sets involved in vasculature development, immune function, and cell adhesion when compared to those in the >30th BWC subcategory. Collectively, our in silico findings suggest that changes in the expression of ARE-containing transcripts in male placentae may contribute to impaired placental vasculature and therefore result in reduced fetal growth outcomes.
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2024 |
Stylianou N, Sebina I, Matigian N, Monkman J, Doehler H, Röhl J, et al., 'Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures', Clinical and Translational Immunology, 13 (2024) [C1]
Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by ... [more]
Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a ¿preeclampsia-like syndrome¿. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection. Methods: We utilised whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n = 9). Results: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS-CoV-2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with¿vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS-CoV-2 samples compared to uninfected controls. Conclusions: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.
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2024 |
Gallo LA, Steane SE, Young SL, de Jersey S, Schoenaker DAJM, Borg DJ, et al., 'Dietary supplements, guideline alignment and biochemical nutrient status in pregnancy: Findings from the Queensland Family Cohort pilot study', Maternal and Child Nutrition, 20 (2024) [C1]
In high-income nations, multiple micronutrient (MMN) supplementation during pregnancy is a common practice. We aimed to describe maternal characteristics associated with supplemen... [more]
In high-income nations, multiple micronutrient (MMN) supplementation during pregnancy is a common practice. We aimed to describe maternal characteristics associated with supplement use and daily dose of supplemental nutrients consumed in pregnancy, and whether guideline alignment and nutrient status are related to supplement use. The Queensland Family Cohort is a prospective, Australian observational longitudinal study. Maternal characteristics, nutrient intake from food and supplements, and biochemical nutrient status were assessed in the second trimester (n = 127). Supplement use was reported by 89% of participants, of whom 91% reported taking an MMN supplement. Participants who received private obstetric care, had private health insurance and had greater alignment to meat/vegetarian alternatives recommendations were more likely to report MMN supplement use. Private obstetric care and general practitioner shared care were associated with higher daily dose of supplemental nutrients consumed compared with midwifery group practice. There was high reliance on supplements to meet nutrient reference values for folate, iodine and iron, but only plasma folate concentrations were higher in MMN supplement versus nonsupplement users. Exceeding the upper level of intake for folic acid and iron was more likely among combined MMN and individual supplement/s users, and associated with higher plasma concentrations of the respective nutrients. Given the low alignment with food group recommendations and potential risks associated with high MMN supplement use, whole food diets should be emphasized. This study confirms the need to define effective strategies for optimizing nutrient intake in pregnancy, especially among those most vulnerable where MMN supplement use may be appropriate.
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Nova |
2024 |
Robinson JL, Gatford KL, Bailey DN, Roff AJ, Clifton VL, Morrison JL, Stark MJ, 'Preclinical models of maternal asthma and progeny outcomes: a scoping review', European Respiratory Review, 33 (2024) [C1]
There is an increased risk of adverse perinatal outcomes in the ~17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes are largely... [more]
There is an increased risk of adverse perinatal outcomes in the ~17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes are largely unknown, but reflect joint effects of genetics and prenatal exposure to maternal asthma. Animal models are essential to understand the underlying mechanisms independent of genetics and comorbidities, and enable safe testing of interventions. This scoping review aimed to explore the methodology, phenotype, characteristics, outcomes and quality of published studies using preclinical maternal asthma models. MEDLINE (PubMed), Embase (Elsevier) and Web of Science were systematically searched using previously validated search strings for maternal asthma and for animal models. Two reviewers independently screened titles and abstracts, full texts, and then extracted and assessed the quality of each study using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) 2.0 guidelines. Out of 3618 studies identified, 39 were eligible for extraction. Most studies were in rodents (86%) and all were models of allergic asthma. Maternal and progeny outcomes included airway hyperresponsiveness, airway resistance, inflammation, lung immune cells, lung structure and serum immunoglobulins and cytokines. Experimental design (100%), procedural details (97%) and rationale (100%) were most often reported. Conversely, data exclusion (21%), blinding (18%) and adverse events (8%) were reported in a minority of studies. Species differences in physiology and timing of development, the use of allergens not relevant to humans and a lack of comparable outcome measures may impede clinical translation. Future studies exploring models of maternal asthma should adhere to the minimum core outcomes set presented in this review.
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2023 |
Dixson BJW, Borg D, Rae KM, Whittingha K, Gannon B, McPhail SM, et al., 'The social predictors of paternal antenatal mental health and their associations with maternal mental health in the Queensland Family Cohort prospective study', Archives of Women's Mental Health, 26 107-116 (2023) [C1]
Antenatal depression (AND) affects 1 in 10 fathers, potentially negatively impacting maternal mental health and well-being during and after the transition to parenthood. However, ... [more]
Antenatal depression (AND) affects 1 in 10 fathers, potentially negatively impacting maternal mental health and well-being during and after the transition to parenthood. However, few studies have assessed the social predictors of paternal AND or their possible associations with maternal mental health. We analysed data from 180 couples participating in the Queensland Family Cohort longitudinal study. Both parents completed surveys measuring mental health, relationship quality, social support, and sleep quality at 24¿weeks of pregnancy. Mothers also completed the same surveys 6¿weeks¿ postpartum. Antenatal depression, stress, and anxiety were highest among fathers reporting lower social support and higher sleep impairment. Maternal AND, stress, and anxiety were higher among mothers reporting higher physical pain and poor sleep quality. Postnatally, mothers reporting lower social support also reported higher depression, anxiety, stress, and psycho-social well-being. While there were no significant associations between AND among fathers and maternal antenatal or postnatal depression, an exploratory analysis revealed that mothers whose partners reported lower antenatal social support also reported lower postnatal social support and higher postnatal depression. Our findings highlight the importance of including data among fathers to achieve a whole family approach to well-being during the transition to parenthood.
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2023 |
Robinson JL, Gatford KL, Clifton VL, Morrison JL, Stark MJ, 'Preclinical models of maternal asthma and progeny outcomes: a scoping review protocol', JBI Evidence Synthesis, 21 2115-2126 (2023)
Objective: This scoping review will describe the methodology, phenotype, and characteristics of maternal asthma models used in preclinical studies and the outcomes that have been ... [more]
Objective: This scoping review will describe the methodology, phenotype, and characteristics of maternal asthma models used in preclinical studies and the outcomes that have been measured in the mother and progeny. The review This will identify gaps in knowledge of maternal and progeny outcomes following maternal asthma in pregnancy. Introduction: Maternal asthma affects up to 17% of pregnancies worldwide and is associated with adverse perinatal outcomes in mothers and babies, including pre-eclampsia, gestational diabetes, cesarean section, preterm birth, small for gestational age, nursery admission, and neonatal death. While the associations are well established, the mechanisms linking maternal asthma and adverse perinatal outcomes are largely unknown due to the difficulties of human mechanistic studies. The appropriate selection of animal models is vital to understanding the mechanisms underlying associations between human maternal asthma and adverse perinatal outcomes. Inclusion criteria: This review will include primary studies published in English where outcomes have been studied in vivo in non-human mammalian species. Methods: This review will follow the JBI methodology for scoping reviews. We will search MEDLINE (PubMed), Embase, and Web of Science to identify papers published before the end of 2022. Initial keywords will include pregnancy, gestation, asthma, and wheeze, as well as validated search strings to identify papers that describe animal models. Extracted data will include information on methods used to induce maternal asthma; asthmatic phenotypes and characteristics; and maternal, pregnancy, placental, and progeny outcomes. The characteristics of each study will be presented in summary tables and a core outcome list to assist researchers in developing, reporting, and comparing future animal studies of maternal asthma. Review registration: Open Science Framework osf.io/trwk5.
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2023 |
Khan A, Inkster AM, Peñaherrera MS, King S, Kildea S, Oberlander TF, et al., 'The application of epiphenotyping approaches to DNA methylation array studies of the human placenta', Epigenetics and Chromatin, 16 (2023) [C1]
Background: Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero ... [more]
Background: Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between cohorts, and understanding and accounting for these factors is essential to ensure meaningful and replicable data analysis. Recently, ¿epiphenotyping¿ approaches have been developed whereby DNAme data can be used to impute information about phenotypic variables such as gestational age, sex, cell composition, and ancestry. These epiphenotypes offer avenues to compare phenotypic data across cohorts, and to understand how phenotypic variables relate to DNAme variability. However, the relationships between placental epiphenotyping variables and other technical and biological variables, and their application to downstream epigenome analyses, have not been well studied. Results: Using DNAme data from 204 placentas across three cohorts, we applied the PlaNET R package to estimate epiphenotypes gestational age, ancestry, and cell composition in these samples. PlaNET ancestry estimates were highly correlated with independent polymorphic ancestry-informative markers, and epigenetic gestational age, on average, was estimated within 4¿days of reported gestational age, underscoring the accuracy of these tools. Cell composition estimates varied both within and between cohorts, as well as over very long placental processing times. Interestingly, the ratio of cytotrophoblast to syncytiotrophoblast proportion decreased with increasing gestational age, and differed slightly by both maternal ethnicity (lower in white vs. non-white) and genetic ancestry (lower in higher probability European ancestry). The cohort of origin and cytotrophoblast proportion were the largest drivers of DNAme variation in this dataset, based on their associations with the first principal component. Conclusions: This work confirms that cohort, array (technical) batch, cell type proportion, self-reported ethnicity, genetic ancestry, and biological sex are important variables to consider in any analyses of Illumina DNAme data. We further demonstrate the specific utility of epiphenotyping tools developed for use with placental DNAme data, and show that these variables (i) provide an independent check of clinically obtained data and (ii) provide a robust approach to compare variables across different datasets. Finally, we present a general framework for the processing and analysis of placental DNAme data, integrating the epiphenotype variables discussed here.
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2023 |
Estrella CAS, Gatford KL, Xiang R, Javadmanesh A, Ghanipoor-Samami M, Nattrass GS, et al., 'Asymmetric growth-limiting development of the female conceptus', Frontiers in Endocrinology, 14 (2023) [C1]
Introduction: Sex differences in prenatal growth may contribute to sex-dependent programming effects on postnatal phenotype. Methods: We integrated for the first time phenotypic, ... [more]
Introduction: Sex differences in prenatal growth may contribute to sex-dependent programming effects on postnatal phenotype. Methods: We integrated for the first time phenotypic, histomorphological, clinico-chemical, endocrine and gene expression analyses in a single species, the bovine conceptus at mid-gestation. Results: We demonstrate that by mid-gestation, before the onset of accelerated growth, the female conceptus displays asymmetric lower growth compared to males. Female fetuses were smaller with lower ponderal index and organ weights than males. However, their brain:body weight, brain:liver weight and heart:body weight ratios were higher than in males, indicating brain and heart ¿sparing¿. The female placenta weighed less and had lower volumes of trophoblast and fetal connective tissue than the male placenta. Female umbilical cord vessel diameters were smaller, and female-specific relationships of body weight and brain:liver weight ratios with cord vessel diameters indicated that the umbilico-placental vascular system creates a growth-limiting environment where blood flow is redistributed to protect brain and heart growth. Clinico-chemical indicators of liver perfusion support this female-specific growth-limiting phenotype, while lower insulin-like growth factor 2 (IGF2) gene expression in brain and heart, and lower circulating IGF2, implicate female-specific modulation of key endocrine mediators by nutrient supply. Conclusion: This mode of female development may increase resilience to environmental perturbations in utero and contribute to sex-bias in programming outcomes including susceptibility to non-communicable diseases.
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2023 |
Leech SM, Gilbert MC, Clifton VL, Kumar S, Rae KM, Borg D, Dekker Nitert M, 'Insufficient Evidence of a Breastmilk Microbiota at Six-Weeks Postpartum: A Pilot Study', Nutrients, 15 (2023) [C1]
Breastmilk is thought to influence the infant gut by supplying prebiotics in the form of human milk oligosaccharides and potentially seeding the gut with breastmilk microbes. Howe... [more]
Breastmilk is thought to influence the infant gut by supplying prebiotics in the form of human milk oligosaccharides and potentially seeding the gut with breastmilk microbes. However, the presence of a breastmilk microbiota and origins of these microbes are still debated. As a pilot study, we assessed the microbes present in expressed breastmilk at six-weeks postpartum using shotgun metagenomic sequencing in a heterogenous cohort of women who delivered by vaginal (n = 8) and caesarean delivery (n = 8). In addition, we estimated the microbial load of breastmilk at six-weeks post-partum with quantitative PCR targeting the 16S rRNA gene. Breastmilk at six-weeks postpartum had a low microbial mass, comparable with PCR no-template and extraction controls. Microbes identified through metagenomic sequencing were largely consistent with skin and oral microbes, with four samples returning no identifiable bacterial sequences. Our results do not provide convincing evidence for the existence of a breastmilk microbiota at six-weeks postpartum. It is more likely that microbes present in breastmilk are sourced by ejection from the infant¿s mouth and from surrounding skin, as well as contamination during sampling and processing.
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2023 |
Whitty JA, Wagner AP, Kang E, Ellwood D, Chaboyer W, Kumar S, et al., 'Cost-effectiveness of closed incision negative pressure wound therapy in preventing surgical site infection among obese women giving birth by caesarean section: An economic evaluation (DRESSING trial)', Australian and New Zealand Journal of Obstetrics and Gynaecology, 63 673-680 (2023) [C1]
Background: There is growing evidence regarding the potential of closed incision negative pressure wound therapy (ci-NPWT) to prevent surgical site infections (SSIs) in healing wo... [more]
Background: There is growing evidence regarding the potential of closed incision negative pressure wound therapy (ci-NPWT) to prevent surgical site infections (SSIs) in healing wounds by primary closure following a caesarean section (CS). Aim: To assess the cost-effectiveness of ci-NPWT compared to standard dressings for prevention of SSI in obese women giving birth by CS. Materials and Methods: Cost-effectiveness and cost-utility analyses from a health service perspective were undertaken alongside a multicentre pragmatic randomised controlled trial, which recruited women with a pre-pregnancy body mass index =30 kg/m2 giving birth by elective/semi-urgent CS who received ci-NPWT (n¿=¿1017) or standard dressings (n¿=¿1018). Resource use and health-related quality of life (SF-12v2) collected during admission and for four weeks post-discharge were used to derive costs and quality-adjusted life years (QALYs). Results: ci-NPWT was associated with AUD$162 (95%CI -$170 to $494) higher cost per person and an additional $12 849 (95%CI -$62 138 to $133 378) per SSI avoided. There was no detectable difference in QALYs between groups; however, there are high levels of uncertainty around both cost and QALY estimates. There is a 20% likelihood that ci-NPWT would be considered cost-effective at a willingness-to-pay threshold of $50 000 per QALY. Per protocol and complete case analyses gave similar results, suggesting that findings are robust to protocol deviators and adjustments for missing data. Conclusions: ci-NPWT for the prevention of SSI in obese women undergoing CS is unlikely to be cost-effective in terms of health service resources and is currently unjustified for routine use for this purpose.
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2023 |
Edwards C, Cavanagh E, Kumar S, Clifton VL, Borg DJ, Priddle J, et al., 'Shear wave velocity measurement of the placenta is not limited by placental location', Placenta, 131 23-27 (2023) [C1]
Introduction: Ultrasound elastography shows diagnostic promise via the non-invasive determination of placental elastic properties. A limitation is a potential for inadequate measu... [more]
Introduction: Ultrasound elastography shows diagnostic promise via the non-invasive determination of placental elastic properties. A limitation is a potential for inadequate measurements from posterior placentae. This study aimed to analyse placental position's influence on measures of shear wave elastography (SWV). Methods: SWV elastography measurements were obtained via ultrasound at 24, 28 and 36 weeks gestation from 238 pregnancies. The placental position was labelled as either anterior, posterior or fundal/lateral. Average SWV measurements (m/s) and the corresponding standard deviations (SD) were used for data analysis. Results: There was a statistically significant difference between SWV recorded from anterior (1.33 ± 0.19)m/s and posterior (1.39 ± 0.18)m/s placentae (p < 0.001). However, the average sampling depth between these groups was significantly different (3.98 cm vs. 5.38 cm, p < 0.001). There was no statistically significant difference between SWV when measurements were compared at similar depths, regardless of placental location. The addition of placental position to a previously developed mixed-effects model confirmed placental position did not result in improved SWV measurements. In this model, sampling depth remained the best predictor for SWV. Conclusions: This study showed that placental position does not influence the accuracy or reliability of SWV.
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2023 |
Bhaumik S, Lockett J, Saif Z, Lai A, Salomon C, Whitehead JP, Clifton VL, 'The impact of obesity and uncontrolled asthma during pregnancy on metabolic and inflammatory pathways', Journal of Asthma, 60 1141-1152 (2023) [C1]
Objective: Asthma and obesity are both inflammatory complications of pregnancy and when combined contribute to an increased risk of uncontrolled asthma during pregnancy and poor p... [more]
Objective: Asthma and obesity are both inflammatory complications of pregnancy and when combined contribute to an increased risk of uncontrolled asthma during pregnancy and poor perinatal outcomes. Our previous work has identified the presence of maternal asthma is associated with a proinflammatory milieu in the placenta and reduced fetal growth. The current study was designed to determine the relationships between immunomodulatory metabolic pathways and inflammation and establish whether these pathways are associated with uncontrolled asthma in obese pregnant women. Methods: Fifty-three obese (BMI >30) pregnant women were recruited prospectively. Participants were classified as having no asthma, controlled asthma, and uncontrolled asthma based on a doctor diagnosis and assessment using the Asthma Control Questionnaire (ACQ). Circulating plasma concentrations of metabolic hormones leptin, adiponectin, insulin, glucose, and extracellular vesicle (EVs) associated cytokines were measured at 18- and 36-weeks gestation. Results: Concentrations of metabolic and inflammatory markers among obese participants with or without asthma were not significantly different throughout gestation. However total adiponectin concentrations increased as gestation progressed in obese, non-asthmatic women but did not increase in women with asthma. Plasma adiponectin and leptin levels in women with uncontrolled asthma were positively correlated with EV inflammatory markers including GM-CSF, IL-6, TNFa and IFN¿ protein. Conclusions: This study demonstrated that most metabolic markers remain unchanged with the presence and severity of asthma in obese pregnant women. However, differences in the associations between metabolic and inflammatory pathways were observed in women with asthma and may be one of the mechanisms contributing to uncontrolled asthma in obese pregnant women.
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2023 |
Robinson JL, Gatford KL, Hurst CP, Clifton VL, Morrison JL, Stark MJ, 'Do improvements in clinical practice guidelines alter pregnancy outcomes in asthmatic women? A single-center retrospective cohort study', Journal of Asthma, 60 1907-1917 (2023) [C1]
Objective: Asthma occurs in ~17% of Australian pregnancies and is associated with adverse perinatal outcomes, which worsen with poor asthma control. Consequently, the South Austra... [more]
Objective: Asthma occurs in ~17% of Australian pregnancies and is associated with adverse perinatal outcomes, which worsen with poor asthma control. Consequently, the South Australian ¿Asthma in Pregnancy¿ perinatal guidelines were revised in 2012 to address management according to severity. This study investigated if these revised guidelines reduced the impact of maternal asthma on risks of adverse perinatal outcomes before (Epoch 1, 2006¿2011) and after the revision (Epoch 2, 2013¿2018). Methods: Routinely collected perinatal and neonatal datasets from the Women¿s and Children¿s Hospital (Adelaide, Australia) were linked. Maternal asthma (prevalence:7.5%) was defined as asthma medication use or symptoms described to midwives. In imputation (n = 59131) and complete case datasets (n = 49594), analyses were conducted by inverse proportional weighting and multivariate logistic regression, accounting for confounders. Results: Overall, maternal asthma was associated with increased risks of any antenatal corticosteroid treatment for threatened preterm birth (aOR 1.319, 95% CI 1.078¿1.614), any Cesarean section (aOR 1.196, 95% CI 1.059¿1.351), Cesarean section without labor (aOR 1.241, 95% CI 1.067¿1.444), intrauterine growth restriction (IUGR, aOR 1.285, 95% CI 1.026¿1.61), and small for gestational age (aOR 1.324, 95% CI 1.136¿1.542). After guideline revision, asthma-associated risks of any Cesarean section (p < 0.001), any antenatal corticosteroids (p = 0.041), and small for gestational age (p = 0.050), but not IUGR and Cesarean section without labor, were reduced. Conclusions: Clinical practice guidelines based on the latest evidence do not guarantee clinical efficacy. Since adverse perinatal outcomes did not all improve, this work highlights the need to evaluate the ongoing impact of guidelines on clinical outcomes.
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2023 |
Bhaumik S, Lockett J, Cuffe J, Clifton VL, 'Glucocorticoids and Their Receptor Isoforms: Roles in Female Reproduction, Pregnancy, and Foetal Development', Biology, 12 (2023) [C1]
Alterations in the hypothalamic¿pituitary¿adrenal (HPA) axis and associated changes in circulating levels of glucocorticoids are integral to an organism¿s response to stressful st... [more]
Alterations in the hypothalamic¿pituitary¿adrenal (HPA) axis and associated changes in circulating levels of glucocorticoids are integral to an organism¿s response to stressful stimuli. Glucocorticoids acting via glucocorticoid receptors (GRs) play a role in fertility, reproduction, placental function, and foetal development. GRs are ubiquitously expressed throughout the female reproductive system and regulate normal reproductive function. Stress-induced glucocorticoids have been shown to inhibit reproduction and affect female gonadal function by suppressing the hypothalamic¿pituitary¿gonadal (HPG) axis at each level. Furthermore, during pregnancy, a mother¿s exposure to prenatal stress or external glucocorticoids can result in long-lasting alterations to the foetal HPA and neuroendocrine function. Several GR isoforms generated via alternative splicing or translation initiation from the GR gene have been identified in the mammalian ovary and uterus. The GR isoforms identified include the splice variants, GRa and GRß, and GR¿ and GR-P. Glucocorticoids can exert both stimulatory and inhibitory effects and both pro- and anti-inflammatory functions in the ovary, in vitro. In the placenta, thirteen GR isoforms have been identified in humans, guinea pigs, sheep, rats, and mice, indicating they are conserved across species and may be important in mediating a differential response to stress. Distinctive responses to glucocorticoids, differential birth outcomes in pregnancy complications, and sex-based variations in the response to stress could all potentially be dependent on a particular GR expression pattern. This comprehensive review provides an overview of the structure and function of the GR in relation to female fertility and reproduction and discusses the changes in the GR and glucocorticoid signalling during pregnancy. To generate this overview, an extensive non-systematic literature search was conducted across multiple databases, including PubMed, Web of Science, and Google Scholar, with a focus on original research articles, meta-analyses, and previous review papers addressing the subject. This review integrates the current understanding of GR variants and their roles in glucocorticoid signalling, reproduction, placental function, and foetal growth.
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2022 |
Clifton VL, Das J, Flenady V, Rae K, 'Response to Letter to the Editor Adverse perinatal outcomes in the Australian Indigenous population, the role of asthma ', Australian and New Zealand Journal of Obstetrics and Gynaecology, 62 E4-E5 (2022)
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2022 |
Edwards C, Cavanagh E, Kumar S, Clifton VL, Borg DJ, Priddle J, et al., 'Relationship between placental elastography, maternal pre-pregnancy body mass index and gestational weight gain', Placenta, 121 1-6 (2022) [C1]
Introduction: Maternal obesity is a significant risk factor for poor pregnancy outcomes. Obesity is linked to abnormalities in placental tissue at term. The purpose of this study ... [more]
Introduction: Maternal obesity is a significant risk factor for poor pregnancy outcomes. Obesity is linked to abnormalities in placental tissue at term. The purpose of this study was to correlate changes in placental stiffness, measured via ultrasound elastography, with maternal pre-pregnancy body mass index and gestational weight gain. Methods: Body Mass Index and gestation weight gain data was collected from 238 women. Elastography measurements were obtained via ultrasound at 24-, 28- and 36-weeks¿ gestation. An analysis using a linear mixed regression model assessed for the statistical significance of pre-pregnancy BMI, pregnancy weight gain and placental SWV (Shear Wave Velocity). Results: Pre-pregnancy weight status has a significant impact on placental tissue stiffness detectable via ultrasound elastography. Placental tissue stiffness was highest in obese women, followed by overweight women. Obese women, on average, had a MeanSWV 0.11 m/s (95% CI (0.061¿0.15) m/s, p < 0.001) above the healthy group throughout the 3rd trimester. Weight gain during pregnancy had a small impact on placental stiffness at the end of pregnancy. MeanSWV was 0.06 m/s (95% CI (0.03¿0.10) m/s, p < 0.001) higher in the excessive weight gain group. Discussion: Structural changes of the placenta detected via ultrasound elastography techniques are not exclusive to placental dysfunction conditions (pre-eclampsia and growth restriction) but are also associated with maternal obesity.
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2022 |
Meakin AS, Gough M, Saif Z, Clifton VL, 'An ex vivo approach to understanding sex-specific differences in placental androgen signalling in the presence and absence of inflammation', Placenta, 120 49-58 (2022) [C1]
Introduction: The mechanisms that contribute to continued male intrauterine growth in response to an adverse maternal environment, such as those brought on by maternal asthma, rem... [more]
Introduction: The mechanisms that contribute to continued male intrauterine growth in response to an adverse maternal environment, such as those brought on by maternal asthma, remain largely undefined but may, in part, be mediated by androgen-mediated signalling. We previously reported the expression of multiple AR protein isoforms in the human placenta and proposed the novel AR-45 isoform to be integral in mediating male-specific androgen-dependent signalling in the presence of maternal asthma. In the current study we have used an ex vivo approach to further understand sex-specific differences in placental androgen signalling in the presence and absence of inflammation using human term villous placental explants. Methods: Explants were cultured in the presence and absence of 0.1 nM dihydrotestosterone (DHT), 1 µg/ml lipopolysaccharide (LPS), or DHT + LPS for 24hr. Tissue was used for gene expression and subcellular AR protein isoform expression. Results: Cytoplasmic and nuclear AR protein isoforms expression did not vary between culture conditions in either sex. AR-45 activity was upregulated in male placentae cultured in DHT, LPS and DHT + LPS only. There were no changes in the expression of androgen-mediated downstream targets in males in response to culture conditions, but females had significantly reduced IGF1R expression in response to LPS. Discussion: Increased AR-45 activity in the presence of inflammation may drive continued male feto-placental growth via maintained expression of downstream growth targets. Our findings build on previous work suggesting an important role for AR-45 in regulating male-specific adaptations to placental inflammation and underscores the need to further characterise the function of this AR isoform.
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2022 |
Mohamad Zainal NH, Mohd Nor NH, Saat A, Clifton VL, 'Childhood allergy susceptibility: The role of the immune system development in the in-utero period', Human Immunology, 83 437-446 (2022) [C1]
Expression of allergic diseases in very early childhood indicates that early life events play a significant role in childhood allergy development. The developmental origins of all... [more]
Expression of allergic diseases in very early childhood indicates that early life events play a significant role in childhood allergy development. The developmental origins of allergy hypothesis suggest events initiated in the in-utero period derived from the interaction between maternal, placental, and fetal factors may contribute to childhood allergy susceptibility. Environmental impacts on placental function and fetal programming are imperative in defining illness risk during pregnancy. Fetal programming, a process by which an injury delivered during a critical period of development, causes immediate adaptive responses with long-term consequences on an organism's structure or function. During pregnancy, the maternal immune response is skewed towards Th2-related humoral responses, hence increasing the susceptibility of childhood allergy development. Maternal atopic phenotype markedly increases the probability of her offspring developing an allergic predisposition. Combination of in utero events ¿ which include maternal asthma or infection, and exposures to maternal allergy which changes the placental function ¿ can alter placental cytokine expression and could predispose offspring to an allergic phenotype. All these events may affect embryology and fetal immune system development. Interestingly, the mechanism and role of the in-utero events on the developmental origins of allergy are not clearly understood; this will be addressed in this review. (199 words)
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2022 |
Das J, Andrews C, Flenady V, Clifton VL, 'Maternal asthma during pregnancy and extremes of body mass index increase the risk of perinatal mortality: a retrospective cohort study', Journal of Asthma, 59 2108-2116 (2022) [C1]
Objective: Asthma during pregnancy and extremes of body mass index (BMI) are independently associated with adverse pregnancy outcomes but the impact of the two conditions combined... [more]
Objective: Asthma during pregnancy and extremes of body mass index (BMI) are independently associated with adverse pregnancy outcomes but the impact of the two conditions combined are currently unknown. The aim of this study was to determine the contribution of maternal BMI to adverse birth outcomes in pregnancies complicated by asthma. Methods: The study utilized the routinely collected perinatal data on births at the Mater Mother¿s Hospital Brisbane, Australia, from January 2008 to December 2019. BMI was grouped as underweight (<18.5), normal weight (18.5-<24.99), overweight (25-29.99), and obese (=30) and the population split by the presence and absence of maternal asthma. The comparison group was normal BMI, non-asthmatic pregnant women. A modified Poisson regression with robust variance was used to estimate the relative risk. Results: In a retrospective cohort study of 110,057 pregnant women, 17.08% of women had asthma. Asthma and BMI were associated with an increased risk of poor fetal and neonatal outcomes. Asthma significantly increased the risk of stillbirth in underweight [adjusted RR: 2.22 (95% CI: 1.25-3.94] and obese [1.74 (1.11-2.71)]; neonatal death in underweight [3.41 (1.89-6.16)] and obese [2.22 (1.37-3.59)] and perinatal death in underweight [2.34 (1.50-3.66)] and obese [1.92 (1.38-2.67)] women. Admission to the neonatal intensive care unit was increased in neonates of underweight [1.65 (1.44-1.89)] and obese [1.26 (1.14-1.40)] asthmatic women. Conclusions: Extremes of BMI, specifically underweight and obesity, increased the risk of adverse perinatal outcomes among asthmatic women highlighting the importance of accounting for BMI during pre-conception and pregnancy related management of asthmatic women.
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2022 |
Clifton VL, Kumar S, Borg D, Rae KM, Boyd RN, Whittingham K, et al., 'Associations between COVID-19 lockdown and post-lockdown on the mental health of pregnant women, postpartum women and their partners from the Queensland family cohort prospective study.', BMC Pregnancy Childbirth, 22 468 (2022) [C1]
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2022 |
Kubler JM, Clifton VL, Moholdt T, Beetham KS, 'The effects of exercise during pregnancy on placental composition: A systematic review and meta-analysis', Placenta, 117 39-46 (2022) [C1]
Introduction: Morphological changes to the placenta occur as the demands of the foetus increase throughout gestation. Physical activity during pregnancy is known to benefit both t... [more]
Introduction: Morphological changes to the placenta occur as the demands of the foetus increase throughout gestation. Physical activity during pregnancy is known to benefit both the mother and infant, however the impact of antenatal exercise training on placental development is less known. The aim of this systematic review and meta-analysis was to investigate the effects of exercise training during pregnancy on measures of placental composition. Methods: Six electronic databases were searched from inception to June 2021 for studies comparing regular antenatal exercise with either usual maternal care or no exercise for its effect on measures of placental morphological composition. Meta-analyses were performed for placental weight and the placental weight to birthweight (PWBW) ratio. Results: Seven randomised controlled trials and two cohort studies were included in the systematic review and meta-analysis (n = 9). There was no significant difference in placental weight (mean difference (MD) = -9.07g, p = 0.42) or the PWBW ratio (MD = 0.00, p = 0.32) between exercise and control groups. Parenchymal tissue volume was higher, represented by an increase in villous tissue, and non-parenchymal volume was lower in women who exercised regularly compared to those that were not exercising during pregnancy. Discussion: Exercise training during pregnancy may not alter placental weight or the PWBW ratio. However, findings from this review indicate that antenatal exercise training can promote advantageous morphological changes to placental tissues.
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2022 |
Wilkinson SA, Schoenaker DAJM, de Jersey S, Collins CE, Gallo L, Rollo M, et al., 'Exploring the diets of mothers and their partners during pregnancy: Findings from the Queensland Family Cohort pilot study', NUTRITION & DIETETICS, 79 602-615 (2022) [C1]
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Nova |
2022 |
Gallo LA, Gallo TF, Borg DJ, Moritz KM, Clifton VL, Kumar S, 'A decline in planned, but not spontaneous, preterm birth rates in a large Australian tertiary maternity centre during COVID-19 mitigation measures', Australian and New Zealand Journal of Obstetrics and Gynaecology, 62 62-70 (2022) [C1]
Background: Reports from around the world suggest that rates of preterm birth decreased during COVID-19 lockdown measures. Aims: To compare the prevalence of preterm birth and sti... [more]
Background: Reports from around the world suggest that rates of preterm birth decreased during COVID-19 lockdown measures. Aims: To compare the prevalence of preterm birth and stillbirth rates during COVID-19 restriction measures with infants born at the same maternity centre during the same weeks in 2013¿2019. Materials and Methods: Deidentified data were extracted from the Mater Mothers¿ healthcare records database. This is a supra-regional tertiary perinatal centre. Logistic regressions were used to examine singleton live preterm birth rates during the beginning of COVID-19 restrictions (16 March-17 April; ¿early¿; 6955 births) and during the strictest part of COVID-19 restrictions (30 March-1 May; ¿late¿; 6953 births), according to gestational age subgroups and birth onset (planned or spontaneous). We adjusted for multiple covariates, including maternal age, body mass index, ethnicity, parity, socioeconomic status, maternal asthma, diabetes mellitus and/or hypertensive disorder. Singleton stillbirth rates were also examined between 16 March¿1 May. Results: Planned moderate/late preterm births declined by more than half during early COVID-19 restrictions compared with the previous seven years (29 vs an average of 64 per 1000 births; adjusted odds ratio 0.39, 95% CI 0.22¿0.71). There was no effect on extremely or very preterm infants, spontaneous preterm births, or stillbirth rates. Rolling averages from January to June revealed a two-week non-significant spike in spontaneous preterm births from late April to early May, 2020. Conclusions: Together with evidence from other nations, the pandemic provides a unique opportunity to identify causal and preventative factors for preterm birth.
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2022 |
Clifton VL, Das J, Flenady V, Rae K, 'Neonatal death is a major concern for Indigenous women with asthma during pregnancy and could be prevented with better models of care', Australian and New Zealand Journal of Obstetrics and Gynaecology, 62 160-163 (2022) [C1]
Asthma is the most common respiratory illness in Aboriginal and Torres Strait Islander Australians. From the Mater Mothers routinely collected perinatal data in Brisbane we have i... [more]
Asthma is the most common respiratory illness in Aboriginal and Torres Strait Islander Australians. From the Mater Mothers routinely collected perinatal data in Brisbane we have identified that 24% of Indigenous and 17% of non-Indigenous women have pregnancies complicated by asthma. Indigenous women with asthma are more likely to have poorer birth outcomes when compared to non-Indigenous women with asthma, with neonatal death being doubled in asthmatic Indigenous women. These data indicate that asthma management during pregnancy is an unmet need for Indigenous women and essential if we are to avoid these devastating outcomes for Indigenous families.
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2022 |
O'Callaghan JL, Clifton VL, Prentis P, Ewing A, Saif Z, Pelzer ES, 'Sex-dependent differential transcript expression in the placenta of growth restricted infants', Placenta, 128 1-8 (2022) [C1]
Introduction: The pathological decrease of fetal growth during gestation can lead to subsequent poor health outcomes for the fetus. This process is commonly controlled by the plac... [more]
Introduction: The pathological decrease of fetal growth during gestation can lead to subsequent poor health outcomes for the fetus. This process is commonly controlled by the placenta, the interface between mother and baby during gestation. Sex-specific gene expression has been implicated in placental function, therefore, there is a need to determine if it is important during reduced fetal growth. We therefore aimed to characterise placental gene expression at term to evaluate sex-specific genetic changes that occur in small for gestational age (SGA) infants. Methods: RNA-sequencing of twelve human placental tissue samples collected from pregnancies yielding either term appropriate for gestational age (AGA) or SGA infants identified at delivery. Candidate genes associated with fetal size and fetal sex were identified using differential gene expression and weighted gene co-expression network analyses. Single-cell sequencing data was used for candidate validation and to estimate candidate transcript expression in specific placental cell populations. Results: Differential gene expression and weighted gene co-expression network analyses identified 403 candidate transcripts associated with SGA infants. One hundred and three of these transcripts showed sex-specific expression. . Published placental sequencing datasets were used to validate the key expression results from the twelve placental samples initially studied; the sex-independent transcript expression for genes involved in cell cycle processes in males (7 transcripts) and endoplasmic reticulum stress in females (17 transcripts). Discussion: This study identified the activation of multiple molecular mechanisms involved in the placental response to an adverse environmental stressor. Mechanisms such as disrupted protein synthesis were shared between infant biological sex when comparing AGA to SGA, whilst other pathways such as cell cycle and endoplasmic reticulum stress appear as independent/specific to either males or females when investigating reduced fetal growth. This data suggests that sexual dimorphism is an important consideration when examining placental dysfunction and poor fetal growth.
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2022 |
Beetham KS, Spathis JG, Hoffmann S, Brown WJ, Clifton V, Mielke GI, 'Longitudinal association of physical activity during pregnancy with maternal and infant outcomes: Findings from the Australian longitudinal study of women s health', Women's Health, 18 (2022) [C1]
Background: Physical activity has known benefits during pregnancy; however, the optimum volume of physical activity through the different stages of pregnancy is not well known. Ob... [more]
Background: Physical activity has known benefits during pregnancy; however, the optimum volume of physical activity through the different stages of pregnancy is not well known. Objectives: The aims of this study were to investigate the associations of physical activity volume in pregnant women in each trimester of pregnancy with maternal and infant outcomes. Design: The study involved 1657 pregnant women from the Australian Longitudinal Study on Women¿s Health, who completed surveys from 2006 to 2012 (aged 28¿39 years). Methods: Women reported being in either the first, second or third trimester of pregnancy. Women were grouped into four groups according to their self-reported physical activity during pregnancy: (1) Nil (0¿<33.3 MET.min/week), (2) Low (33.3¿<500 MET.min/week), (3) Moderate (500¿<1000 MET.min/week) and (4) High (¿1000 MET.min/week). Women who reported their physical activity during pregnancy completed a survey within three years after the birth, relating to outcomes associated with pregnancy and childbirth (gestational diabetes, hypertension, and antenatal depression and anxiety) and infant outcomes (birthweight and prematurity). Results: There was no association of physical activity in any trimester with infant birthweight, prematurity, gestational diabetes, hypertension or antenatal depression. Antenatal anxiety was less prevalent in women who reported low (1.7%) or moderate (1.1%) physical activity than in those who reported no activity (4.7%; p = 0.01). Conclusion: Different amounts of physical activity during pregnancy were not associated with the measured adverse health outcomes. However, low and moderate amounts of physical activity were associated with reduced incidence of antenatal anxiety.
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2022 |
Rad HS, Röhl J, Stylianou N, Allenby MC, Bazaz SR, Warkiani ME, et al., 'Corrigendum: The effects of COVID-19 on the placenta during pregnancy(Front. Immunol., (2021), 12, (743022), 10.3389/fimmu.2021.743022)', Frontiers in Immunology, 13 (2022)
In the published article (31) was not cited in the article. The citation has now been inserted in Transplacental Viral Transmission, paragraph two, the corrected paragraph appears... [more]
In the published article (31) was not cited in the article. The citation has now been inserted in Transplacental Viral Transmission, paragraph two, the corrected paragraph appears below.
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2021 |
Tamanna S, Clifton VL, Rae K, van Helden DF, Lumbers ER, Pringle KG, 'Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age (vol 11, 590787, 2020)', FRONTIERS IN PHYSIOLOGY, 12 (2021)
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2021 |
Borg D, Rae K, Fiveash C, Schagen J, James-Mcalpine J, Friedlander F, et al., 'Queensland Family Cohort: A study protocol', BMJ Open, 11 (2021)
Introduction The perinatal-postnatal family environment is associated with childhood outcomes including impacts on physical and mental health and educational attainment. Family lo... [more]
Introduction The perinatal-postnatal family environment is associated with childhood outcomes including impacts on physical and mental health and educational attainment. Family longitudinal cohort studies collect in-depth data that can capture the influence of an era on family lifestyle, mental health, chronic disease, education and financial stability to enable identification of gaps in society and provide the evidence for changes in government in policy and practice. Methods and analysis The Queensland Family Cohort (QFC) is a prospective, observational, longitudinal study that will recruit 12 500 pregnant families across the state of Queensland (QLD), Australia and intends to follow-up families and children for three decades. To identify the immediate and future health requirements of the QLD population; pregnant participants and their partners will be enrolled by 24 weeks of gestation and followed up at 24, 28 and 36 weeks of gestation, during delivery, on-ward, 6 weeks postpartum and then every 12 months where questionnaires, biological samples and physical measures will be collected from parents and children. To examine the impact of environmental exposures on families, data related to environmental pollution, household pollution and employment exposures will be linked to pregnancy and health outcomes. Where feasible, data linkage of state and federal government databases will be used to follow the participants long term. Biological samples will be stored long term for future discoveries of biomarkers of health and disease. Ethics and dissemination Ethical approval has been obtained from the Mater Research Ethics (HREC/16/MHS/113). Findings will be reported to (1) QFC participating families; (2) funding bodies, institutes and hospitals supporting the QFC; (3) federal, state and local governments to inform policy; (4) presented at local, national and international conferences and (5) disseminated by peer-review publications.
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2021 |
Bartho LA, O'Callaghan JL, Fisher JJ, Cuffe JSM, Kaitu'u-Lino TJ, Hannan NJ, et al., 'Analysis of mitochondrial regulatory transcripts in publicly available datasets with validation in placentae from pre-term, post-term and fetal growth restriction pregnancies', Placenta, 112 162-171 (2021) [C1]
Introduction: The human placenta has a defined lifespan and placental aging is a key feature as pregnancy progresses. Placental aging and mitochondrial dysfunction are known to pl... [more]
Introduction: The human placenta has a defined lifespan and placental aging is a key feature as pregnancy progresses. Placental aging and mitochondrial dysfunction are known to play a key role in pregnancy pathophysiology. Premature aging of the placenta has also been linked with placental dysfunction resulting in poor fetal development and premature birth. Methods: The expression of key mitochondrial-related genes were analysed in a series of publicly available databases then expression changes were validated in placental samples collected from term, pre-term, post-term pregnancies and pregnancies complicated by fetal growth restriction (FGR). Gene and protein expression levels of MFN1, MFN2, TFAM, TOMM20, OPA3 and SIRT4 were measured in placental tissues via qPCR and western blotting. Results: Initial analysis found that key mitochondrial transcripts related to biogenesis, bioenergetics and mitophagy clustered by pregnancy trimester. A refined list of 13 mitochondrial-related genes were investigated in additional external datasets of pregnancy complications. In the new cohort, protein expression of MFN1 was decreased in FGR and MFN2 is decreased in post-term placenta. Analysis of placental tissues revealed that TOMM20 gene and protein expression was altered in FGR and post-term placenta. Discussion: MFN1 and MFN2 play a major role in mitochondrial dynamics, and alterations in these markers have been highlighted in early unexplained miscarriage. TOMM20 is an importer protein that plays a major role in mitophagy and changes have also been identified in age-related diseases. Significant changes in MFN1, MFN2 and TOMM20 indicate that mitochondrial regulators play a critical role in placental aging and placental pathophysiology.
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Nova |
2021 |
Bokern MP, Robijn AL, Jensen ME, Barker D, Callaway L, Clifton V, et al., 'Factors Associated with Asthma Exacerbations During Pregnancy', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, 9 4343-+ (2021) [C1]
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Nova |
2021 |
Chi C, Fan Y, Li C, Li Y, Guo S, Li T, et al., 'Early gut microbiota colonisation of premature infants fed with breastmilk or formula with or without probiotics: A cohort study', Nutrients, 13 (2021) [C1]
Premature infants have a fragile ecology of the gut microbiota, which is associated with many health problems and may be influenced by formula versus breast feeding. The present s... [more]
Premature infants have a fragile ecology of the gut microbiota, which is associated with many health problems and may be influenced by formula versus breast feeding. The present study investigated differences in the process of gut microbiota colonisation in preterm infants fed with breastmilk or formula with or without probiotics before 12 weeks. This cohort study recruited 138 premature infants; 31 in the breastmilk (BM) group, 59 in the probiotics formula (PF) group and 48 in the non-probiotics formula (NPF) group, according to the feeding practice they received at birth. Gut bacterial composition was identified with 16S rRNA gene sequencing in faecal samples collected at 1 week, 6 weeks and 12 weeks after birth. The alpha diversity was higher in the PF group compared to the other groups at week 1 and 6 (both p < 0.01) but showed no difference at week 12. The beta diversity of the three groups showed a trend towards similarity at the first two stages (p < 0.001 and p = 0.009, respectively) and finally showed no difference at week 12. Canonical redundancy analysis showed that feeding type could explain the difference in gut microbiota composition at week one and six (both p < 0.01). At genus level, Bifidobacterium was enriched in the PF group, while the Enterococcus and Streptococcus was enriched in the NPF group. In summary, formula with probiotics feeding after birth can affect gut microbiota colonisation and lead to a bacterial community with less potential pathogens.
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2021 |
Robijn AL, Barker D, Gibson PG, Giles WB, Clifton VL, Mattes J, et al., 'Factors Associated with Nonadherence to Inhaled Corticosteroids for Asthma During Pregnancy', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, 9 1242-+ (2021) [C1]
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Nova |
2021 |
Saif Z, Meakin AS, Clifton VL, 'A preferential switch between placental GR exon 1 promoter variants in the presence of maternal asthma or inflammation upregulates GRa D isoforms', Placenta, 108 64-72 (2021) [C1]
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2021 |
Meakin AS, Morrison JL, Bradshaw EL, Holman SL, Saif Z, Gatford KL, et al., 'Identification of placental androgen receptor isoforms in a sheep model of maternal allergic asthma', Placenta, 104 232-235 (2021) [C1]
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2021 |
Gillespie BM, Webster J, Ellwood D, Thalib L, Whitty JA, Mahomed K, et al., 'Closed incision negative pressure wound therapy versus standard dressings in obese women undergoing caesarean section: Multicentre parallel group randomised controlled trial', The BMJ, 373 (2021) [C1]
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Nova |
2021 |
Skuse A, Rodger D, Wilmore M, Humphreys S, Dalton J, Clifton V, 'Solving wicked problems in the app co-design process', Convergence, 27 539-553 (2021) [C1]
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2021 |
Young SL, Saif Z, Meakin AS, McMaster ES, Hayes N, Gallo LA, et al., 'Alterations to Placental Glucocorticoid Receptor Expression with Alcohol Consumption', Reproductive Sciences, 28 1390-1402 (2021) [C1]
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2021 |
Edwards C, Cavanagh E, Kumar S, Clifton V, Fontanarosa D, 'Intra-system reliability assessment of 2-dimensional shear wave elastography', Applied Sciences (Switzerland), 11 (2021) [C1]
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2021 |
Jensen ME, Robijn AL, Gibson PG, Oldmeadow C, Clifton V, Giles W, et al., 'Longitudinal Analysis of Lung Function in Pregnant Women with and without Asthma', Journal of Allergy and Clinical Immunology: In Practice, 9 1578-1585.e3 (2021) [C1]
Background: Spirometry is commonly used to assess and monitor lung function. It may also be a useful tool to monitor maternal health during pregnancy. However, large studies exami... [more]
Background: Spirometry is commonly used to assess and monitor lung function. It may also be a useful tool to monitor maternal health during pregnancy. However, large studies examining lung function across gestation are limited. Also, whether spirometry values follow the same pattern during pregnancy in women with and without asthma is unknown. Objective: To investigate the effect of advancing gestation, and its interaction with asthma, on lung function in a large well-defined cohort of pregnant women. Methods: Data were obtained from prospective cohorts involving women with (n = 770) and without (n = 259) asthma (2004-2017), recruited between 12 and 22 weeks' gestation. Lung function (forced vital capacity [FVC], FEV1, FEV1:FVC%) was assessed periodically during pregnancy using spirometry. Multilevel mixed-effect regression models were used to assess changes in lung function over gestation. Results: Asthma had a significant effect on baseline lung function (FEV1%, -9%; FVC%, -3%; FEV1:FVC%, -4%). FVC% decreased with advancing gestation (-0.07%/wk; 95% CI, -0.10 to -0.04]), as did FEV1%, but only among those without asthma (women without asthma: -0.14%/wk, 95% CI, -0.22 to -0.06%; compared with women with asthma: 0.02%/wk, 95% CI, -0.01 to 0.06). FEV1:FVC% remained relatively stable for women without asthma (0.03%/wk; 95% CI, -0.08 to 0.02), but increased for women with asthma (0.06%/wk; 95% CI, 0.04 to 0.16). Conclusions: Data suggest that advancing gestation negatively affects FVC% and FEV1%. This is consistent with extrapulmonary restriction from advancing pregnancy. Yet, the presence of asthma altered the trajectories of FEV1% and FEV1:FVC%. Optimal asthma management during pregnancy might have opposed the negative effects of gestation on lung function.
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Nova |
2021 |
Steane SE, Young SL, Clifton VL, Gallo LA, Akison LK, Moritz KM, 'Prenatal alcohol consumption and placental outcomes: a systematic review and meta-analysis of clinical studies', American Journal of Obstetrics and Gynecology, 225 607.e1-607.e22 (2021) [C1]
Objective: A systematic review was conducted to determine placental outcomes following prenatal alcohol exposure in women. Data Sources: The search terms ¿maternal OR prenatal OR ... [more]
Objective: A systematic review was conducted to determine placental outcomes following prenatal alcohol exposure in women. Data Sources: The search terms ¿maternal OR prenatal OR pregnant OR periconception¿ AND ¿placenta¿ AND ¿alcohol OR ethanol¿ were used across 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and CINAHL) from inception until November 2020. Study Eligibility Criteria: Articles were included if they reported placental outcomes in an alcohol exposure group compared with a control group. Studies were excluded if placentas were from elective termination before 20 weeks¿ gestation, animal studies, in vitro studies, case studies, or coexposure studies. Methods: Study quality was assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale. Title and abstract screening was conducted by 2 reviewers to remove duplicates and irrelevant studies. Remaining full text articles were screened by 2 reviewers against inclusion and exclusion criteria. Placental outcome data were extracted and tabulated separately for studies of placentation, placental weight, placental morphology, and placental molecular studies. Meta-analyses were conducted for outcomes reported by >3 studies. Results: Database searching retrieved 640 unique records. Screening against inclusion and exclusion criteria resulted in 33 included studies. The quality assessment identified that 61% of studies were high quality, 30% were average quality, and 9% were low quality. Meta-analyses indicated that prenatal alcohol exposure increased the likelihood of placental abruption (odds ratio, 1.48; 95% confidence interval, 1.37¿1.60) but not placenta previa (odds ratio, 1.14; 95% confidence interval, 0.84¿1.34) and resulted in a reduction in placental weight of 51 g (95% confidence interval, -82.8 to -19.3). Reports of altered placental vasculature, placental DNA methylation, and gene expression following prenatal alcohol exposure were identified. A single study examined placentas from male and female infants separately and found sex-specific placental outcomes. Conclusion: Prenatal alcohol exposure increases the likelihood of placental abruption and is associated with decreased placental weight, altered placental vasculature, DNA methylation, and molecular pathways. Given the critical role of the placenta in determining pregnancy outcomes, further studies investigating the molecular mechanisms underlying alcohol-induced placental dysfunction are required. Sex-specific placental adaptations to adverse conditions in utero have been well documented; thus, future studies should examine prenatal alcohol exposure¿associated placental outcomes separately by sex.
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2021 |
Roff AJ, Morrison JL, Tai A, Clifton VL, Gatford KL, 'Maternal asthma during pregnancy and risks of allergy and asthma in progeny: A systematic review protocol', JBI Evidence Synthesis, 19 2007-2013 (2021)
Objective:The primary objective of this systematic review is to synthesize the best available evidence on the relationship between in utero exposure to maternal asthma and postnat... [more]
Objective:The primary objective of this systematic review is to synthesize the best available evidence on the relationship between in utero exposure to maternal asthma and postnatal allergy. Secondary objectives are to investigate the impact of asthma loss of control, asthma exacerbation, and asthma severity during pregnancy on risks of allergy and asthma in progeny.Introduction:Maternal asthma is a well-known risk factor for childhood asthma, with recent evidence suggesting that children of asthmatic mothers are also at increased risk of allergic diseases. Importantly, these do not appear to be purely genetic associations, since maternal asthma is more strongly associated with childhood asthma than paternal asthma. In addition, experimentally induced allergic asthma during pregnancy increases allergic responses to sensitization in mice. The strength of the relationships between exposure to maternal asthma or severity of maternal asthma, and progeny asthma and allergy are unknown.Inclusion criteria:This review will include primary studies that report incidence of physician-diagnosed asthma or allergic disease in human progeny who were exposed in utero to maternal asthma, in comparison to progeny not exposed to maternal asthma.Methods:Initial search terms include (pregnan* OR gestat*) AND asthma* AND allerg*. We will search the following electronic databases for published and unpublished evidence: PubMed, Embase, MEDLINE (Ovid), Web of Science, Cochrane Library, CINAHL, Scopus, Informit Health, MedNar, ProQuest, and Trove. There will be no restrictions on publication date. Only studies available as a full-text English publication will be considered for inclusion.Systematic review registration number:PROSPERO CRD42020201538.
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2021 |
Meakin AS, Cuffe JSM, Darby JRT, Morrison JL, Clifton VL, 'Let s talk about placental sex, baby: Understanding mechanisms that drive female-and male-specific fetal growth and developmental outcomes', International Journal of Molecular Sciences, 22 (2021) [C1]
It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developm... [more]
It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that the male prioritises growth pathways in order to maximise growth through to adulthood, thereby ensuring the greatest chance of reproductive success. However, this male-specific ¿evolutionary advantage¿ likely contributes to males being less adaptable to shifts in the in-utero environment, which then places them at a greater risk for intrauterine morbidities or mortality. Comparatively, females are more adaptable to changes in the in-utero environment at the cost of growth, which may reduce their risk of poor perinatal outcomes. The mechanisms that drive these sex-specific adaptations to a change in the in-utero environment remain unclear, but an increasing body of evidence within the field of developmental biology would suggest that alterations to placental function, as well as the feto-placental hormonal milieu, is an important contributing factor. Herein, we have addressed the current knowledge regarding sex-specific intrauterine growth differences and have examined how certain pregnancy complications may alter these female-and male-specific adaptations.
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2021 |
Rad HS, Röhl J, Stylianou N, Allenby MC, Bazaz SR, Warkiani ME, et al., 'The Effects of COVID-19 on the Placenta During Pregnancy', Frontiers in Immunology, 12 (2021) [C1]
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs ... [more]
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.
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2021 |
Edwards C, Cavanagh E, Kumar S, Clifton VL, Borg DJ, Priddle J, et al., 'Changes in placental elastography in the third trimester - Analysis using a linear mixed effect model', Placenta, 114 83-89 (2021) [C1]
Introduction: Research into the role of ultrasound elastography to assess compromised placental tissue is ongoing. There is particular interest in evaluating its potential in the ... [more]
Introduction: Research into the role of ultrasound elastography to assess compromised placental tissue is ongoing. There is particular interest in evaluating its potential in the investigation of changes associated with uteroplacental dysfunction. To date, there is limited data on how different maternal and fetal considerations, such as advancing gestational age, amniotic fluid Index (AFI) and maternal body mass index (BMI) may influence shear wave velocity (SWV) measurements. This study aimed to evaluate longitudinal changes in SWV throughout gestation and model these changes with other developing fetal and maternal physiological and biological characteristics. Methods: The study utilised 238 singleton pregnancies and collected longitudinal data at repeated intervals in the 3rd trimester representing 629 individual data points. Linear mixed model regression analysis was used to identify significant predictors for SWV. Results: From a total of ten variables selected for modelling, only gestational age, AFI, BMI, and sample depth were found to be significant predictors of placental SWV, and gestational age and AFI were found to have only a minimal impact on SWV. Discussion: Sophisticated statistical modelling demonstrates that many of the expected maternal and fetal changes in the 3rd trimester have no or minimal impact on placental SWV. Understanding which factors influence placental SWV is essential to ascertain the technique's utility in managing pregnancies complicated by placental dysfunction in the future.
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2021 |
McKeating DR, Clifton VL, Hurst CP, Fisher JJ, Bennett WW, Perkins AV, 'Elemental Metabolomics for Prediction of Term Gestational Outcomes Utilising 18-Week Maternal Plasma and Urine Samples', Biological Trace Element Research, 199 26-40 (2021) [C1]
A normal pregnancy is essential to establishing a healthy start to life. Complications during have been associated with adverse perinatal outcomes and lifelong health problems. Th... [more]
A normal pregnancy is essential to establishing a healthy start to life. Complications during have been associated with adverse perinatal outcomes and lifelong health problems. The ability to identify risk factors associated with pregnancy complications early in gestation is vitally important for preventing negative foetal outcomes. Maternal nutrition has been long considered vital to a healthy pregnancy, with micronutrients and trace elements heavily implicated in maternofoetal metabolism. This study proposed the use of elemental metabolomics to study multiple elements at 18¿weeks gestation from blood plasma and urine to construct models that could predict outcomes such as small for gestational age (SGA) (n = 10), low placental weight (n = 18), and preterm birth (n = 13) from control samples (n = 87). Samples collected from the Lyell McEwin Hospital in Adelaide, South Australia, were measured for 27 plasma elements and 37 urine elements by inductively coupled plasma mass spectrometry. Exploratory analysis indicated an average selenium concentration 20¿µg/L lower than established reference ranges across all groups, low zinc in preterm (0.64¿µg/L, reference range 0.66¿1.10¿µg/L), and higher iodine in preterm and SGA gestations (preterm 102¿µg/L, SGA 111¿µg/L, reference range 40¿92¿µg/L). Using random forest algorithms with receiver operating characteristic curves, low placental weight was predicted with 86.7% accuracy using plasma, 78.6% prediction for SGA with urine, and 73.5% determination of preterm pregnancies. This study indicates that elemental metabolomic modelling could provide a means of early detection of at-risk pregnancies allowing for more targeted monitoring of mothers, with potential for early intervention strategies to be developed.
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2021 |
Gannon B, Jayawardana D, Clifton V, 'Descriptive Data Analysis of Inequality of Economic Opportunity using the Queensland Family Cohort Pilot Study', Australian Economic Review, 54 398-405 (2021) [C1]
The Queensland Family Cohort Pilot Study follows 450 women over the course of their pregnancy and after giving birth, collecting a wealth of information on socioeconomic character... [more]
The Queensland Family Cohort Pilot Study follows 450 women over the course of their pregnancy and after giving birth, collecting a wealth of information on socioeconomic characteristics, health, healthcare use and biological samples. The focus of this paper is to demonstrate how these data may be used to measure inequality of opportunity, between advantaged and disadvantaged populations, for mothers, partners and babies, in terms of their mental health and use of scarce health care resources. This paper provides the foundation for future analyses when a wider Queensland study is proposed to collect data from 12,500 families.
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2020 |
Edwards C, Cavanagh E, Kumar S, Clifton V, Fontanarosa D, 'The use of elastography in placental research A literature review', Placenta, 99 78-88 (2020)
Introduction: Ultrasound elastography is a technique used to quantify biomechanical changes that occur in parenchymal tissue with disease. Recent research has applied the techniqu... [more]
Introduction: Ultrasound elastography is a technique used to quantify biomechanical changes that occur in parenchymal tissue with disease. Recent research has applied the technique to the placenta in order to investigate changes associated with uteroplacental dysfunction. We performed a literature review to summarise the current available information regarding this novel technique. Methods: Pubmed, CINAHL and Embase were searched using the terms ¿placenta¿, ¿ultrasound¿ and ¿elastography¿. Only full text studies written in English and limited to placental sonoelastography were included. Results: Twenty-eight studies met the inclusion criteria and were included in this review. Publications were divided into in vivo and ex vivo groups, and further categorised into four subgroups: normal pregnancy, pregnancy-induced hypertension and pre-eclampsia, fetal growth restriction and other pregnancy complications. Conclusion: Ultrasound elastography can quantitatively assess biomechanical properties of the placenta in conditions where placental function is compromised.
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2020 |
Abdollahi E, Saghafi N, Rezaee SAR, Rastin M, Jarahi L, Clifton V, Rafatpanah H, 'Evaluation of 1,25(Oh)2d3 effects on foxp3, ror- t, gitr, and ctla-4 gene expression in the pbmcs of vitamin d-deficient women with unexplained recurrent pregnancy loss (urpl)', Iranian Biomedical Journal, 24 290-300 (2020)
Background: Vitamin D insufficiency and deficiency can be associated with adverse effects on fetus and pregnancy outcomes. This study aimed at evaluating the effect of 1,25VitD3 o... [more]
Background: Vitamin D insufficiency and deficiency can be associated with adverse effects on fetus and pregnancy outcomes. This study aimed at evaluating the effect of 1,25VitD3 on specific transcription factor and markers of Tregs and Th17 cells in the PBMCs of women with URPL as a case group and the PBMCs of healthy women as a control group. Methods: Samples from 20 non-pregnant patients with a history of URPL were compared to 20 normal non-pregnant women. PBMCs were divided into three wells for each subject in the presence of 1,25VitD3 (50 nM, for 16 hours), PHA (10 µM; positive control) and without any treatment (negative control). By Real-time PCR (Taqman assay), specific transcription factors of Tregs and Th17 cells, FOXP3, ROR-¿t, GITR, and CTLA-4 mRNA expressions in two groups were measured. Results: FOXP3/ROR-¿t mRNA expression in PBMCs decreased significantly in women experiencing URPL compared to the control group (p = 0.0001). Although 1,25VitD3 (50 nM) increased FOXP3 gene expression (p = 0.0001), it did not significantly affect ROR-¿t gene expression. 1,25VitD3 treatment significantly increased FOXP3/ROR-¿t mRNA expression from baseline in the PBMCs of the fetal loss group compared to that of the control group (p = 0.01). The 1,25VitD3 also increased GITR gene expression (p = 0.017) in the PBMCs of URPL women compared to the controls. Conclusion: Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests that the supplementation of women with Vitamin D pre-pregnancy may be protective against URPL via affecting Tregs signature genes, FOXP3 and GITR.
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2020 |
Meakin AS, Saif Z, Seedat N, Clifton VL, 'The impact of maternal asthma during pregnancy on fetal growth and development: a review', Expert Review of Respiratory Medicine, 14 1207-1216 (2020)
Introduction: Asthma is a highly prevalent co-morbidity during pregnancy that can worsen as gestation progresses and is associated with several adverse perinatal outcomes. These a... [more]
Introduction: Asthma is a highly prevalent co-morbidity during pregnancy that can worsen as gestation progresses and is associated with several adverse perinatal outcomes. These adverse outcomes often result from uncontrolled asthma during pregnancy and acute asthma exacerbations that are associated with alterations in placental function and fetal growth. Areas covered: This paper will discuss how maternal asthma in pregnancy affects fetal growth and development which may alter future offspring health. Changes in placental function occur in a sex-specific manner in pregnancies complicated by asthma and result in differences in fetal growth and development which may influence child health. The follow up of children from mothers with asthma suggests they are at greater risk of developing asthma, have alterations in microvascular structure that may contribute to a future risk of cardiovascular disease and epigenetic modifications in immune cell function. The current evidence suggests that appropriately managed asthma during pregnancy results in normal fetal growth and development. Expert opinion: Clinical management of asthma during pregnancy needs significant improvement to prevent adverse outcomes for the fetus. The key to improving maternal and fetal outcomes is through education of health professionals and parents about controlling asthma during pregnancy.
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2020 |
Jones AR, Tuckwell C, Wright IMR, Morrison JL, Kandasamy Y, Wittwer MR, et al., 'The impact of maternal asthma during pregnancy on offspring retinal microvascular structure and its relationship to placental growth factor production in utero', Microcirculation, 27 (2020) [C1]
Asthma is a common chronic disease in pregnancy that affects placental function and fetal growth and associated with cardio-metabolic disorders in the offspring but the mechanisms... [more]
Asthma is a common chronic disease in pregnancy that affects placental function and fetal growth and associated with cardio-metabolic disorders in the offspring but the mechanisms are unknown. This study explored whether maternal asthma in pregnancy is associated with the development of offspring microvascular structure and whether it was related to biomarkers of angiogenesis in utero. Children aged 4 to 6¿years, born to either asthmatic mothers (n¿=¿38) or healthy controls (n¿=¿25), had their retinal microvascular structure examined. Maternal plasma PlGF concentrations at 18 and 36¿weeks¿ gestation were measured. There was a significant global difference in all retinal microvascular measures between children of asthmatic mothers relative to controls and increased retinal venular tortuosity in children born to asthmatic mothers (7.1 (95% CI 0.7-13.5); P¿=.031). A rise in plasma PlGF from 18 to 36¿weeks¿ gestation was observed in the control population which was significantly lower in the asthma group by 190.9¿pg/mL. PlGF concentrations were correlated with microvascular structure including arteriolar branching and venular tortuosity. These exploratory findings indicate that exposure to maternal asthma during pregnancy is associated with persistent changes in microvascular structure in childhood that may be driven by alterations to angiogenic mechanisms in utero.
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2020 |
O Callaghan JL, Clifton VL, Prentis P, Ewing A, Miller YD, Pelzer ES, 'Modulation of placental gene expression in small-for-gestational-age infants', Genes, 11 (2020) [C1]
Small-for-gestational-age (SGA) infants are fetuses that have not reached their genetically programmed growth potential. Low birth weight predisposes these infants to an increased... [more]
Small-for-gestational-age (SGA) infants are fetuses that have not reached their genetically programmed growth potential. Low birth weight predisposes these infants to an increased risk of developing cardiovascular, metabolic and neurodevelopmental conditions in later life. However, our understanding of how this pathology occurs is currently incomplete. Previous research has focused on understanding the transcriptome, epigenome and bacterial signatures separately. However, we hypothesise that interactions between moderators of gene expression are critical to understanding fetal growth restriction. Through a review of the current literature, we identify that there is evidence of modulated expression/methylation of the placental genome and the presence of bacterial DNA in the placental tissue of SGA infants. We also identify that despite limited evidence of the interactions between the above results, there are promising suggestions of a relationship between bacterial signatures and placental function. This review aims to summarise the current literature concerning fetal growth from multiple avenues and propose a novel relationship between the placental transcriptome, methylome and bacterial signature that, if characterised, may be able to improve our current understanding of the placental response to stress and the aetiology of growth restriction.
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2020 |
O Callaghan JL, Turner R, Dekker Nitert M, Barrett HL, Clifton V, Pelzer ES, 'Re-assessing microbiomes in the low-biomass reproductive niche', BJOG: An International Journal of Obstetrics and Gynaecology, 127 147-158 (2020) [C1]
The female reproductive tract represents a continuum between the vagina and the upper genital tract. New evidence from cultivation-independent studies suggests that the female upp... [more]
The female reproductive tract represents a continuum between the vagina and the upper genital tract. New evidence from cultivation-independent studies suggests that the female upper genital tract is not sterile; however, the significance of this for reproductive health and disease remains to be elucidated fully. Further, diagnosis and treatment of infectious reproductive tract pathologies using cultivation-independent technologies represents a largely unchartered area of modern medical science. The challenge now is to design well-controlled experiments to account for the ease of contamination known to confound molecular-based studies of low-biomass niches, including the uterus and placenta. This will support robust assessment of the potential function of microorganisms, microbial metabolites, and cell-free bacterial DNA on reproductive function in health and disease. Tweetable abstract: Molecular microbial studies of low-biomass niches require stringent experimental controls to reveal causal relations in reproductive health and disease.
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2020 |
Tamanna S, Clifton VL, Rae K, van Helden DF, Lumbers ER, Pringle KG, 'Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age', Frontiers in Physiology, 11 1-10 (2020) [C1]
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Nova |
2020 |
Flenady VJ, Middleton P, Wallace E, Morris J, Gordon A, Boyle FM, et al., 'Stillbirth in Australia 1: The road to now: Two decades of stillbirth research and advocacy in Australia', Women and Birth, 33 506-513 (2020)
Stillbirth is a major public health problem with an enormous mortality burden and psychosocial impact on parents, families and the wider community both globally and in Australia. ... [more]
Stillbirth is a major public health problem with an enormous mortality burden and psychosocial impact on parents, families and the wider community both globally and in Australia. In 2015, Australia's late gestation stillbirth rate was over 30% higher than that of the best-performing countries globally, highlighting the urgent need for action. We present an overview of the foundations which led to the establishment of Australia's NHMRC Centre of Research Excellence in Stillbirth (Stillbirth CRE) in 2017 and highlight key activities in the following areas: Opportunities to expand and improve collaborations between research teams; Supporting the conduct and development of innovative, high quality, collaborative research that incorporates a strong parent voice; Promoting effective translation of research into health policy and/or practice; and the Regional and global work of the Stillbirth CRE. We highlight the first-ever Senate Inquiry into Stillbirth in Australia in 2018. These events ultimately led to the development of a National Stillbirth Action and Implementation Plan for Australia with the aims of reducing stillbirth rates by 20% over the next five years, reducing the disparity in stillbirth rates between advantaged and disadvantaged communities, and improving care for all families who experience this loss.
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2020 |
Abdollahi E, Rezaee SA, Saghafi N, Rastin M, Clifton V, Sahebkar A, Rafatpanah H, 'Evaluation of the effects of 1,25 vitamin d3 on regulatory t cells and t helper 17 cells in vitamin d-deficient women with unexplained recurrent pregnancy loss', Current Molecular Pharmacology, 13 306-317 (2020)
Background: Vitamin D insufficiency and deficiency can be associated with adverse effects on pregnancy outcomes, which may include recurrent pregnancy loss through the mechanisms ... [more]
Background: Vitamin D insufficiency and deficiency can be associated with adverse effects on pregnancy outcomes, which may include recurrent pregnancy loss through the mechanisms that are yet unknown. The aim of this study was to evaluate the effect of 1,25VitD3 on regulatory T cells (Tregs) and T helper17 (Th17) cell populations In vitro in unexplained recurrent pregnancy loss (URPL) patients and healthy women. Methods: Samples from 20 non-pregnant women with a history of URPL were compared to 20 normal non-pregnant women. Peripheral blood mononuclear cells (PBMC) were divided into 3 wells for each subject: in the presence of 1, 25 VitD3 (50 nM, for 16 hours), PHA (positive control) (10µM), and without any treatment (as a baseline or negative control). The percentage of regulatory T cells and Th17 cells was measured by flow cytometry at baseline and then after cell culture ex-periments. Results: Our study indicated that the percentage of Tregs in patients with URPL was significantly lower than the control group (2.42 ± 0.27 vs. 3.41 ± 0.29, P= 0.01). The percentage of Th17 cells was significantly greater in URPL patients compared to the control group (2.91 ± 0.33 vs. 1.18± 0.15, P=0.001). 1, 25VitD3 treatment significantly increased the percentage of Tregs from the baseline in the URPL group compared to that in the control group (1.23 ± 0.03 vs. 1.00 ± 0.03, P= 0.01). Conclusion: Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests supplementation of women with Vit D pre-pregnancy may be protective against URPL.
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2019 |
Wooldridge AL, Clifton VL, Moss TJM, Lu H, Jamali M, Agostino S, et al., 'Maternal allergic asthma during pregnancy alters fetal lung and immune development in sheep: potential mechanisms for programming asthma and allergy', Journal of Physiology, 597 4251-4262 (2019)
Key points: Experimental maternal allergic asthma in sheep provides an experimental model in which to test impacts on progeny. Fetuses from allergic asthmatic ewes had fewer surfa... [more]
Key points: Experimental maternal allergic asthma in sheep provides an experimental model in which to test impacts on progeny. Fetuses from allergic asthmatic ewes had fewer surfactant-producing cells in lungs. A greater proportion of lymphocytes from thymus were CD44 positive in fetuses from allergic asthmatic ewes than in controls. These changes to fetal development might contribute to poor neonatal lung function and increased risk of allergy seen in offspring of pregnancies complicated by asthma. Abstract: Asthma is prevalent in pregnancy and increases the risk of disease in offspring, including neonatal respiratory distress and childhood asthma and allergy, but the mechanisms are not understood. We hypothesized that fetal lung structure and immune phenotype in late gestation fetal sheep would be impaired in our sheep model of maternal allergic asthma during pregnancy. Singleton-bearing ewes were either sensitized before pregnancy to house dust mite (HDM, allergic, n¿=¿7) or were non-allergic (control, n¿=¿5). The ewes were subsequently subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Tissues were collected at 140¿±¿1¿days gestational age (term, ~147¿days). The density of type II alveolar epithelial cells (surfactant protein C-immunostained) in the lungs was 30% lower in fetuses from allergic ewes than in controls (P¿<¿0.001), but tissue-to-air space ratio and numbers of leucocytes and macrophages were not different between groups. The proportion of CD44+ lymphocytes in the fetal thymus was 3.5-fold higher in fetuses from allergic ewes than in control ewes (P¿=¿0.043). Fewer surfactant-producing type II alveolar epithelial cells may contribute to the increased risk of neonatal respiratory distress in infants of asthmatic mothers, suggesting that interventions to promote lung maturation could improve their neonatal outcomes. If the elevated lymphocyte expression of CD44 persists postnatally, this would confer greater susceptibility to allergic diseases in progeny of asthmatic mothers, consistent with observations in humans. Further experiments are needed to evaluate postnatal phenotypes of progeny and investigate potential interventions.
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2019 |
Clifton VL, McDonald M, Morrison JL, Holman SL, Lock MC, Saif Z, et al., 'Placental glucocorticoid receptor isoforms in a sheep model of maternal allergic asthma', Placenta, 83 33-36 (2019)
Maternal asthma increases the risk of adverse pregnancy outcomes and may affect fetal growth and placental function by differential effects on the expression of glucocorticoid rec... [more]
Maternal asthma increases the risk of adverse pregnancy outcomes and may affect fetal growth and placental function by differential effects on the expression of glucocorticoid receptor (GR) isoforms, leading to altered glucocorticoid signalling. Our aim was to examine the effect of maternal asthma on placental GR profiles using a pregnant sheep model of asthma. Nine known GR isoforms were detected. There was a significant increase in the expression of placental GR isoforms that are known to have low trans-activational activity in other species including GR A, GR P and GR¿ which may result in a pro-inflammatory environment in the presence of allergic asthma.
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2019 |
Beetham KS, Giles C, Noetel M, Clifton V, Jones JC, Naughton G, 'The effects of vigorous intensity exercise in the third trimester of pregnancy: A systematic review and meta-analysis', BMC Pregnancy and Childbirth, 19 (2019)
Background: Fetal growth is dependent upon utero-placental vascular supply of oxygen and nutrients from the mother and has been proposed to be compromised by vigorous intensity ex... [more]
Background: Fetal growth is dependent upon utero-placental vascular supply of oxygen and nutrients from the mother and has been proposed to be compromised by vigorous intensity exercise in the third trimester. The aim of this systematic review was to investigate the effects of vigorous intensity exercise performed throughout pregnancy, on infant and maternal outcomes. Methods: Electronic searching of the PubMed, Medline, EMBASE, Cochrane Library, Web of Science and CINAHL databases was used to conduct the search up to November 2018. Study designs included in the systematic review were randomised control trials, quasi-experimental studies, cohort studies and case-control studies. The studies were required to include an intervention or report of pregnant women performing vigorous exercise during gestation, with a comparator group of either lower intensity exercise or standard care. Results: Ten cohort studies (n = 32,080) and five randomized control trials (n = 623) were included in the systematic review (n = 15), with 13 studies included in the meta-analysis. No significant difference existed in birthweight for infants of mothers who engaged in vigorous physical activity and those who lacked this exposure (mean difference = 8.06 g, n = 8006). Moreover, no significant increase existed in risk of small for gestational age (risk ratio = 0.15, n = 4504), risk of low birth weight (< 2500 g) (risk ratio = 0.44, n = 2454) or maternal weight gain (mean difference = - 0.46 kg, n = 1834). Women who engaged in vigorous physical activity had a small but significant increase in length of gestational age before delivery (mean difference = 0.21 weeks, n = 4281) and a small but significantly reduced risk of prematurity (risk ratio = - 0.20, n = 3025). Conclusions: Findings from this meta-analysis indicate that vigorous intensity exercise completed into the third trimester appears to be safe for most healthy pregnancies. Further research is needed on the effects of vigorous intensity exercise in the first and second trimester, and of exercise intensity exceeding 90% of maximum heart rate. Trial registration: PROSPERO trial registration CRD42018102109.
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2019 |
Grieger JA, Pelecanos AM, Hurst C, Tai A, Clifton VL, 'Pre-conception maternal food intake and the association with childhood allergies', Nutrients, 11 (2019)
Background: Periconceptional nutrition may have an important function in programming the immune function and allergies, however, there is a lack of studies assessing pre-conceptio... [more]
Background: Periconceptional nutrition may have an important function in programming the immune function and allergies, however, there is a lack of studies assessing pre-conception food intake and childhood allergic disorders. The aim of the current study was to identify maternal pre-conception dietary components that may be associated with allergic disorders in children up to 3 years of age. Methods: Pregnant women attending their first antenatal visit and who were aged >18 years were invited to participate. Pre-conception food frequency data was retrospectively collected at 18 weeks¿ gestation. Childhood eczema, current wheeze, and rhinitis was assessed at 36 months of age using a questionnaire and doctor diagnosis (n = 234). Linear discriminant analysis (LDA) was used to explore the combination of dietary food components that best discriminated between allergy status in children. Results: Maternal pre-conception food intake such as low and high fat dairy, fresh fruit, unsaturated spreads, and take-away foods, were protective for any allergy assessed. Non-oily fish was protective for eczema and current wheeze; saturated spreads (e.g., butter) was protective for eczema, current wheeze, and rhinitis; poultry and fruit juice were adversely associated with each allergy. Conclusions: Pre-conception food intakes demonstrate inconsistent and somewhat contrary relationships to the development of child allergies. Whether and how maternal food intake impacts the underlying fetal programming and the mechanisms of childhood allergy warrants further investigation.
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2019 |
Meakin AS, Saif Z, Tuck AR, Clifton VL, 'Human placental androgen receptor variants: Potential regulators of male fetal growth', Placenta, 80 18-26 (2019)
Introduction: Numerous studies show that males have increased intrauterine growth compared to females, and that pregnancy complications may further these growth differences, but t... [more]
Introduction: Numerous studies show that males have increased intrauterine growth compared to females, and that pregnancy complications may further these growth differences, but the regulatory mechanisms underlying these differences remain unknown. We propose that these growth outcomes may be due to sex-specific differences in androgen sensitivity ¿ giving rise to altered growth signalling pathways ¿ mediated by the differential expression of placental androgen receptor (AR) variants. Methods: Placental protein and mRNA were used to identify AR protein variant levels and AR-downstream target gene expression, and were then analysed against neonatal measurements. Dihydrotestosterone (DHT)-induced AR protein variant expression and downstream growth factors were examined in vitro. Results: Four known AR variants (AR-FL, AR-V1, AR-V7, and AR-45), and three unknown proteins (120, 90 and 55 kDa) immunoreactive to the anti-AR antibody were identified in human placentae. Male placentae from controlled asthmatic pregnancies had increased AR-45 and decreased AR-V1 and AR-V7 nuclear expression. Increased nuclear AR-45 expression was associated with increased insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), and IGF-binding protein 5 (IGFBP-5) mRNA expression and normal male growth. AR-45 mRNA and protein did not change in the presence of uncontrolled maternal asthma and associated with an increase in small for gestational (SGA) male fetuses. In vitro DHT stimulation increased AR-45 protein and IGF-1R and IGFBP-5 mRNA expression. Conclusions: Collectively, our data shows altered AR protein expression and downstream signalling targets may contribute to sex-specific fetal growth outcomes in response to an adverse environment, and that AR-45 appears central in mediating these changes.
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2019 |
Tucker J, Murphy EMA, Steen M, Clifton VL, 'Understanding what impacts on disclosing anal incontinence for women when comparing bowel-screening tools: A phenomenological study', BMC Women's Health, 19 (2019)
Background: There is limited research defining the true prevalence of anal incontinence (AI) in women of childbearing age. Understanding the limitations of the current assessment ... [more]
Background: There is limited research defining the true prevalence of anal incontinence (AI) in women of childbearing age. Understanding the limitations of the current assessment tools in the identification of AI is paramount for identifying the prevalence of AI and improving the care and management for women of childbearing age. The aim of this research was to explore and develop an understanding of women's experiences in disclosing AI when completing a new bowel-screening questionnaire when compared to two established AI tools. Methods: A phenomenological qualitative research study was undertaken in a maternity setting in a large tertiary hospital. Parous women in the first trimester of a subsequent pregnancy were recruited to complete a specifically designed screening tool (BSQ), St Marks Faecal incontinence score (Vaizey) and Cleveland (Wexner) score. Qualitative semi-structured interviews were utilised to identify experiences in disclosing AI. Results: Women (n = 16, 22-42 years) with a history of anal incontinence either following the first birth (n = 12) or the second (n = 4) provided differing responses between the three assessment tools. All women answered the BSQ while the Vaizey and Wexner scores were more difficult to complete due to clinical language and participants level of comprehension. Women identified three major themes that were barriers for disclosing incontinence, which included social expectations, trusted space and confusion. Conclusion: There are barriers for disclosing AI in the pregnant and post-natal population, which can be improved with the use of an easy assessment tool. The BSQ may facilitate discussion on AI between the patient and health professional leading to earlier identification and improvement in short and long-term health outcomes.
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2019 |
Meakin AS, Clifton VL, 'Review: Understanding the role of androgens and placental AR variants: Insight into steroid-dependent fetal-placental growth and development', Placenta, 84 63-68 (2019)
The role of steroids throughout pregnancy and their effect on placental physiology is well established, especially for estrogens, progestogens, and glucocorticoids; however, the r... [more]
The role of steroids throughout pregnancy and their effect on placental physiology is well established, especially for estrogens, progestogens, and glucocorticoids; however, the role of androgens ¿ particularly within the context of placental physiology ¿ remains largely unexplored. Androgens are often defined as the male sex-steroids and are fundamental for the defeminisation and masculinisation of male fetuses. Therefore, the placenta may adapt to these steroids in a sex-specific manner, with males being more receptive to changes in these steroids concentrations, when compared with females; however, their involvement in female intrauterine development has been investigated in several studies and may suggest females have a level of responsiveness to these steroids. While the former may be true, studies have reported sex-specific differences in the expression and activity of factors involved in androgen biosynthesis and bioavailability, with males consistently demonstrating greater degrees of altered protein and gene expression when compared with females. Understanding the placental androgen axis is essential as many pregnancy comorbidities are associated with elevated concentrations of androgens and perturbed intrauterine development or growth. Indeed, it appears that specific pathophysiologies of pregnancy can modulate the activity of key factors involved in the placental androgen axis and this may contribute to the etiology of sex-specific developmental outcomes from certain pregnancy complications. This review will provide insight into what is currently known regarding androgen signalling and the human placenta, and how this complex system may regulate sex-specific growth and developmental outcomes in normal and adverse pregnancies.
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2019 |
Robijn AL, Jensen ME, Gibson PG, Powell H, Giles WB, Clifton VL, et al., 'Trends in asthma self-management skills and inhaled corticosteroid use during pregnancy and postpartum from 2004 to 2017.', The Journal of asthma : official journal of the Association for the Care of Asthma, 56 594-602 (2019) [C1]
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Nova |
2019 |
Clifton VL, 'Managing asthma in pregnancy: effects on future child health', The Lancet Respiratory Medicine, 7 485-486 (2019)
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2018 |
Grzeskowiak LE, Grieger JA, Clifton VL, 'Strategies towards improving pharmacological management of asthma during pregnancy', Pharmacological Research, 130 85-92 (2018)
Maternal asthma represents a significant burden to individuals and the healthcare system, affecting 1 in 10 pregnancies worldwide. Approximately 50% of asthmatic women experience ... [more]
Maternal asthma represents a significant burden to individuals and the healthcare system, affecting 1 in 10 pregnancies worldwide. Approximately 50% of asthmatic women experience a deterioration of asthma control at some stage during pregnancy, with a number requiring use of oral corticosteroids for the management of acute exacerbations. The presence of maternal asthma and exacerbations during pregnancy is a noted risk factor for a range of adverse perinatal outcomes including preterm birth, small-for-gestational age, pre-eclampsia, and gestational diabetes. These negative impacts highlight the need for evidence-based approaches for improving asthma management during pregnancy and subsequent perinatal outcomes. Despite this, relatively small progress has been made in enhancing the management of maternal asthma in the clinical setting. A major challenge in improving outcomes of asthmatic pregnancies is that there is no single simplified approach for improving outcomes, but rather the requirement to consider the dynamic relationship between a myriad of interrelated factors that ultimately determine an individual's ability to maintain adequate asthma control. Understanding how these factors are impacted by pregnancy and how they can be addressed through various interventions is therefore important in optimising health outcomes. This review summarises key factors involved in influencing outcomes associated with maternal asthma. This includes an overview of the use of asthma medications in pregnancy, while also considering the impacts of interrelated aspects such as medication adherence, health-seeking behaviours, biological and lifestyle factors, co-morbidities, and asthma self-management strategies on asthma control. Addressing such factors through multidisciplinary approaches towards treatment have potential to improve the health of mothers and their offspring. Optimising asthma control should be a high priority within the antenatal setting, with women advised about the importance of good asthma control, managing asthma actively throughout pregnancy by utilising their asthma medications, and managing exacerbations in a timely and effective manner.
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2018 |
Sherrell H, Dunn L, Clifton V, Kumar S, 'Systematic review of maternal Placental Growth Factor levels in late pregnancy as a predictor of adverse intrapartum and perinatal outcomes', European Journal of Obstetrics and Gynecology and Reproductive Biology, 225 26-34 (2018)
Aim: This systematic review evaluates the utility of maternal Placental Growth Factor (PlGF) when measured in late pregnancy (>20 weeks) as a predictor of adverse obstetric and... [more]
Aim: This systematic review evaluates the utility of maternal Placental Growth Factor (PlGF) when measured in late pregnancy (>20 weeks) as a predictor of adverse obstetric and perinatal outcomes. Methods: Pubmed and Embase were searched using the term ¿placental growth factor¿ in combination with relevant perinatal outcomes. Studies were included if they measured PlGF levels in pregnant women after 20 + 0 weeks gestation and reported relevant adverse obstetric or perinatal outcomes related to placental insufficiency (excluding pre-eclampsia). Results: Twenty-six studies were eligible for inclusion with 21 studies investigating the relationship between PlGF and small for gestational age (SGA) and 7 studies investigating PlGF for the prediction of other adverse perinatal outcomes. In all studies, maternal PlGF levels were significantly lower in the SGA group compared to controls. Other outcomes investigated included caesarean section (CS) for fetal compromise, low Apgar score, neonatal intensive care unit (NICU) admission, neonatal acidosis, stillbirth, and intrapartum fetal compromise. The results generally showed a significant association between low PlGF levels and CS for fetal compromise, NICU admission and stillbirth. Conclusion: Low maternal PlGF levels in late pregnancy are strongly associated with SGA. Findings across studies were variable in relation to PlGF and the prediction of other adverse intrapartum and perinatal outcomes, however there was a consistent association between low PlGF levels and CS for fetal compromise, NICU admission and stillbirth. This review suggests that the use of PlGF for the prediction of adverse outcomes is promising. Its predictive value may potentially be enhanced if used in combination with other biomarkers or biophysical measures of fetal well-being.
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2018 |
Wooldridge AL, Bischof RJ, Liu H, Heinemann GK, Hunter DS, Giles LC, et al., 'Late-gestation maternal dietary methyl donor and cofactor supplementation in sheep partially reverses protection against allergic sensitization by IUGR', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 314 R22-R33 (2018)
Perinatal exposures are associated with altered risks of childhood allergy. Human studies and our previous work suggest that restricted growth in utero (IUGR) is protective agains... [more]
Perinatal exposures are associated with altered risks of childhood allergy. Human studies and our previous work suggest that restricted growth in utero (IUGR) is protective against allergic disease. The mechanisms are not clearly defined, but reduced fetal abundance and altered metabolism of methyl donors are hypothesized as possible underlying mechanisms. Therefore, we examined whether late-gestation maternal dietary methyl donor and cofactor supplementation of the placentally restricted (PR) sheep pregnancy would reverse allergic protection in progeny. Allergic outcomes were compared between progeny from control pregnancies (CON; n < 49), from PR pregnancies without intervention (PR; n < 28), and from PR pregnancies where the dam was fed a methyl donor plus cofactor supplement from day 120 of pregnancy until delivery (PR - Methyl; n < 25). Both PR and PR - Methyl progeny were smaller than CON; supplementation did not alter birth size. PR was protective against cutaneous hypersensitivity responses to ovalbumin (OVA; P < 0.01 in singletons). Cutaneous hypersensitivity responses to OVA in PR - Methyl progeny were intermediate to and not different from the responses of CON and PR sheep. Cutaneous hypersensitivity responses to house dust mites did not differ between treatments. In singleton progeny, upper dermal mast cell density was greater in PR - Methyl than in PR or CON (each P < 0.05). The differences in the cutaneous allergic response were not explained by treatment effects on circulating immune cells or antibodies. Our results suggest that mechanisms underlying in utero programming of allergic susceptibility by IUGR and methyl donor availability may differ and imply that late-gestation methyl donor supplementation may increase allergy risk.
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2018 |
Sherrell H, Clifton V, Kumar S, 'Predicting intrapartum fetal compromise at term using the cerebroplacental ratio and placental growth factor levels (PROMISE) study: Randomised controlled trial protocol', BMJ Open, 8 (2018)
Introduction Intrapartum complications are a major contributor to adverse perinatal outcomes, including stillbirth, hypoxic-ischaemic brain injury and subsequent longer term disab... [more]
Introduction Intrapartum complications are a major contributor to adverse perinatal outcomes, including stillbirth, hypoxic-ischaemic brain injury and subsequent longer term disability. In many cases, hypoxia develops as a gradual process due to the inability of the fetus to tolerate the stress of parturition suggesting reduced fetoplacental reserve before labour commences. The fetal cerebroplacental ratio (CPR) is an independent predictor of intrapartum fetal compromise, poor acid base status at birth and of neonatal unit admission at term. Similarly, circulating maternal levels of placental growth factor (PlGF) are lower in pregnancies complicated by placental dysfunction. This paper outlines the protocol for the PROMISE Study, which aims to determine if the introduction of a prelabour screening test for intrapartum fetal compromise combining the CPR and maternal PlGF level results in a reduction of adverse perinatal outcomes. Methods and analysis This is a single-site, non-blinded, individual patient randomised controlled trial of a screening test performed at term, combining the fetal CPR and maternal serum PlGF. Women with a singleton, non-anomalous pregnancy will be recruited after 34 weeks' gestation and randomised to either receive the screening test or not. Screened pregnancies determined to be at risk will be recommended induction of labour. Demographic, obstetric history and antenatal data will be collected at enrolment, and perinatal outcomes will be recorded after delivery. Relative risks and 95% CIs will be reported for the primary outcome. Regression techniques will be used to examine the influence of prognostic factors on the primary and secondary outcomes. Ethics and dissemination This study has been reviewed and approved by the Mater Human Research Ethics Committee (Reference: HREC EC00332) and will follow the principles of Good Clinical Practice. The study results will be disseminated at national and international conferences and published in peer-reviewed journals. Trial registration number ACTRN12616001009404; Pre-results.
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2018 |
Albers L, Sobotzki C, Kuß O, Ajslev T, Batista RF, Bettiol H, et al., 'Maternal smoking during pregnancy and offspring overweight: is there a dose response relationship? An individual patient data meta-analysis', International Journal of Obesity, 42 1249-1264 (2018)
Background/objectives: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose¿respons... [more]
Background/objectives: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose¿response relationship across number of cigarettes and whether this differs by sex remains unclear. Subject/methods: Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex. Results: Of 26 identified studies, 16 authors provided data on a total of 238,340 mother¿child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02¿1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results. Conclusions: A linear dose¿response relationship of maternal smoking was observed in the range of 1¿15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.
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2018 |
Albers L, von Kries R, Sobotzki C, Gao HJ, Buka SL, Clifton VL, et al., 'Differences in maternal smoking across successive pregnancies dose-dependent relation to BMI z-score in the offspring: an individual patient data (IPD) meta-analysis', Obesity Reviews, 19 1248-1255 (2018)
Introduction: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective w... [more]
Introduction: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear. Methods: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose¿response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations. Results: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses =25 cigarettes per day. Conclusions: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.
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2018 |
Grzeskowiak LE, Smithers LG, Grieger JA, Bianco-Miotto T, Leemaqz SY, Clifton VL, et al., 'Asthma treatment impacts time to pregnancy: Evidence from the international SCOPE study', European Respiratory Journal, 51 (2018)
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2018 |
Dalton JA, Rodger D, Wilmore M, Humphreys S, Skuse A, Roberts CT, Clifton VL, 'The Health-e Babies App for antenatal education: Feasibility for socially disadvantaged women', PLoS ONE, 13 (2018)
Background The use of mobile technology such as phone applications (apps) has been proposed as an efficient means of providing health and clinical information in a variety of heal... [more]
Background The use of mobile technology such as phone applications (apps) has been proposed as an efficient means of providing health and clinical information in a variety of healthcare settings. We developed the Health-e Babies app as an Android smart phone application for pregnant women attending a tertiary hospital in a low socio-economic community, with the objective of providing health information about early pregnancy that would increase maternal confidence and reduce anxiety. Based on our earlier research, this form of health communication was viewed as a preferred source of information for women of reproductive age. However, the pilot study had a poor participation rate with 76% (n = 94) not completing the study requirements. These initial findings raised some very important issues in relation to the difficulties of engaging women with a pregnancy app. This paper analyses the characteristics of the participants who did not complete the study requirements in an attempt to identify potential barriers associated with the implementation of a pregnancy app. Methods This retrospective review of quantitative and qualitative data collected at the commencement of the Health-e Babies App trial, related to the participant¿s communication technology use, confidence in knowing where to seek help and mental health status, maternal-fetal attachment and parenting confidence. Engagement and use of the Health-e Babies App was measured by the completion of a questionnaire about the app and downloaded data from participant¿s phones. Mental health status, confidence and self-efficacy were measured by questionnaires Results All women were similar in terms of age, race, marital status and level of education. Of the 94 women (76%) who did not complete the trial, they were significantly more anxious as indicated by State Trait Anxiety Inventory (p = 0.001 Student T-test) and more likely to be unemployed (50% vs 31%, p = 0.012 Student T-Test). Conclusion This study provides important information about the challenges associated with the implementation of a pregnancy app in a socially disadvantaged community. The data suggests that factors including social and mental health issues, financial constraints and technological ability can affect women¿s engagement with a mobile phone app.
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2017 |
Adibi J, Burton GJ, Clifton V, Collins S, Frias AE, Gierman L, et al., 'IFPA meeting 2016 workshop report II: Placental imaging, placenta and development of other organs, sexual dimorphism in placental function and trophoblast cell lines', PLACENTA, 60 S10-S14 (2017)
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2017 |
Clifton VL, Cuffe J, Moritz KM, Cole TJ, Fuller PJ, Lu NZ, et al., 'Review: The role of multiple placental glucocorticoid receptor isoforms in adapting to the maternal environment and regulating fetal growth', Placenta, 54 24-29 (2017)
The physiological mechanisms that confer different outcomes in morbidity and mortality of the fetus exposed to stressful environments may be driven by significant differences in t... [more]
The physiological mechanisms that confer different outcomes in morbidity and mortality of the fetus exposed to stressful environments may be driven by significant differences in the expression and function of the placental glucocorticoid receptor (GR). The recent discovery that the placenta contains at least 8 different isoforms of the GR raises questions about the regulation and physiological relevance of the many GR variants expressed in the placenta. The current data also highlights that individual differences in glucocorticoid sensitivity, variations in the effect of different complications of pregnancy on birth outcomes and sex differences in the response to stress, may all be dependent on a specific GR isoform expression profile. This review will investigate the current state of knowledge of GR isoforms in the placenta and discuss the potential role of these multiple isoforms in regulating glucocorticoid sensitivity.
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2017 |
Akison LK, Nitert MD, Clifton VL, Moritz KM, Simmons DG, 'Review: Alterations in placental glycogen deposition in complicated pregnancies: Current preclinical and clinical evidence', Placenta, 54 52-58 (2017)
Normal placental function is essential for optimal fetal growth. Transport of glucose from mother to fetus is critical for fetal nutrient demands and can be stored in the placenta... [more]
Normal placental function is essential for optimal fetal growth. Transport of glucose from mother to fetus is critical for fetal nutrient demands and can be stored in the placenta as glycogen. However, the function of this glycogen deposition remains a matter of debate: It could be a source of fuel for the placenta itself or a storage reservoir for later use by the fetus in times of need. While the significance of placental glycogen remains elusive, mounting evidence indicates that altered glycogen metabolism and/or deposition accompanies many pregnancy complications that adversely affect fetal development. This review will summarize histological, biochemical and molecular evidence that glycogen accumulates in a) placentas from a variety of experimental rodent models of perturbed pregnancy, including maternal alcohol exposure, glucocorticoid exposure, dietary deficiencies and hypoxia and b) placentas from human pregnancies with complications including preeclampsia, gestational diabetes mellitus and intrauterine growth restriction (IUGR). These pregnancies typically result in altered fetal growth, developmental abnormalities and/or disease outcomes in offspring. Collectively, this evidence suggests that changes in placental glycogen deposition is a common feature of pregnancy complications, particularly those associated with altered fetal growth.
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2017 |
Meakin AS, Saif Z, Jones AR, Aviles PFV, Clifton VL, 'Review: Placental adaptations to the presence of maternal asthma during pregnancy', Placenta, 54 17-23 (2017)
Asthma is a highly prevalent chronic medical condition affecting an estimated 12% of pregnant, women each year, with prevalence of asthma greatest (up to 16%) among the socially d... [more]
Asthma is a highly prevalent chronic medical condition affecting an estimated 12% of pregnant, women each year, with prevalence of asthma greatest (up to 16%) among the socially disadvantaged. Maternal asthma is associated with significant perinatal morbidity and mortality including preterm births, neonatal hospitalisations and low birthweight outcomes each year. We have identified that the placenta adapts to the presence of chronic, maternal asthma during pregnancy in a sex specific manner that may confer sex differences in fetal outcome. The male fetus was at greater risk of a poor outcome than a female fetus in the presence of maternal asthma and an acute inflammatory event such as an asthma exacerbation. This review will examine the role of sex specific differences in placental function on fetal growth and survival.
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2017 |
Clifton VL, 'Preface', Placenta, 54 1 (2017)
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2017 |
Gatford KL, Wooldridge AL, Kind KL, Bischof R, Clifton VL, 'Pre-birth origins of allergy and asthma', Journal of Reproductive Immunology, 123 88-93 (2017)
Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, ... [more]
Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, a crude marker of the fetal environment, and allergy have been reported in humans and require comprehensive review. Associations between birth weight and allergy are however confounded in humans, and we and others have therefore begun exploring the effects of early life events on allergy in experimental models. In particular, we are using ovine models to investigate whether and how a restricted environment before birth protects against allergy, whether methyl donor availability contributes to allergic protection in IUGR, and why maternal asthma during pregnancy is associated with increased risks of allergic disease in children. We found that experimental intrauterine growth restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny, despite normal or elevated IgE responses. Furthermore, maternal methyl donor supplementation in late pregnancy partially reversed effects of experimental IUGR, consistent with the proposal that epigenetic pathways underlie some but not all effects of IUGR on allergic susceptibility. Ovine experimental allergic asthma with exacerbations reduces relative fetal size in late gestation, with some changes in immune populations in fetal thymus suggestive of increased activation. Maternal allergic asthma in mice also predisposes progeny to allergy development. In conclusion, these findings in experimental models provide direct evidence that a perturbed environment before birth alters immune system development and postnatal function, and provide opportunities to investigate underlying mechanisms and develop and evaluate interventions.
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2017 |
Schubert KO, Air T, Clark SR, Grzeskowiak LE, Miller E, Dekker GA, et al., 'Trajectories of anxiety and health related quality of life during pregnancy', PLoS ONE, 12 (2017)
Anxiety and health related Quality of Life (HRQoL) have emerged as important mental health measures in obstetric care. Few studies have systematically examined the longitudinal tr... [more]
Anxiety and health related Quality of Life (HRQoL) have emerged as important mental health measures in obstetric care. Few studies have systematically examined the longitudinal trajectories of anxiety and HRQoL in pregnancy. Using a linear growth modeling strategy, we analyzed the course of State-Trait Anxiety Inventory (STAI)- and Short Form (36) Health Survey (SF-36) scores between the 12th and the 36th week of gestation, in a sample of 355 women. We additionally analyzed the impact of depressive symptoms and a chronic medical condition (asthma), on STAI and SF-36 trajectory curves. STAI scores remained stable throughout pregnancy. A previous history of anxiety increased the overall STAI scores. Asthma and depressive symptoms scores had no impact on the STAI trajectory. Physical SF-36 scores decreased over the course of pregnancy, whereas mental SF-36 trended towards improvement. Asthma reduced physical SF-36 overall. While high depressive symptoms decreased the overall mental SF-36, they were also significantly associated with mental SF-36 improvements over time. Anxiety symptoms are stable during pregnancy and are not modulated by depressive symptoms or asthma. Physical HRQoL declines in pregnancy. In contrast, mental HRQoL appears to improve, particularly in women with high initial levels of depressive symptoms.
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2017 |
Tucker J, Grzeskowiak L, Murphy EMA, Wilson A, Clifton VL, 'Do women of reproductive age presenting with pelvic floor dysfunction have undisclosed anal incontinence: A retrospective cohort study', Women and Birth, 30 18-22 (2017)
Background Indirect and direct trauma following vaginal birth can negatively impact on the pelvic floor function increasing the risk of anal incontinence. It is often difficult fo... [more]
Background Indirect and direct trauma following vaginal birth can negatively impact on the pelvic floor function increasing the risk of anal incontinence. It is often difficult for women to openly disclose that they have anal incontinence and there are limited data collection tools available for the identification of these women in a clinical setting. Aim This study aims to describe the prevalence of undisclosed anal incontinence in antenatal and postnatal women with pelvic floor dysfunction. Methods Retrospective cohort study of 230 antenatal and postnatal women referred to a Continence Nursing Service in a large tertiary hospital in South Australia, Australia, with pelvic floor dysfunction. A criteria list was utilised to access the primary reason for referral, anal incontinence assessments and attendance to an appointment. Results Anal incontinence was identified in 26% of women (n¿=¿59). Anal incontinence was the primary reason for referral amongst 8 women, with the remaining 51 women identified as having anal incontinence following clinical screening via phone consultation. Eighty six percent of women stated they had not previously disclosed anal incontinence to health professionals. Overall, 71% of symptomatic women (n¿=¿28 antenatal and n¿=¿14 postnatal women) attended appointments to a service specialising in pelvic floor dysfunction. Conclusion Women presenting with urinary incontinence or other markers of pelvic floor dysfunction should be actively screened for anal incontinence as the prevalence of this condition is high amongst childbearing women.
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2017 |
Buckberry S, Bianco-Miotto T, Bent SJ, Clifton V, Shoubridge C, Shankar K, Roberts CT, 'Placental transcriptome co-expression analysis reveals conserved regulatory programs across gestation', BMC Genomics, 18 (2017)
Background: Mammalian development in utero is absolutely dependent on proper placental development, which is ultimately regulated by the placental genome. The regulation of the pl... [more]
Background: Mammalian development in utero is absolutely dependent on proper placental development, which is ultimately regulated by the placental genome. The regulation of the placental genome can be directly studied by exploring the underlying organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. Results: In this study, we performed a comprehensive analysis of human placental co-expression using RNA sequencing and intergrated multiple transcriptome datasets spanning human gestation. We identified modules of co-expressed genes that are preserved across human gestation, and also identifed modules conserved in the mouse indicating conserved molecular networks involved in placental development and gene expression patterns more specific to late gestation. Analysis of co-expressed gene flanking sequences indicated that conserved co-expression modules in the placenta are regulated by a core set of transcription factors, including ZNF423 and EBF1. Additionally, we identified a gene co-expression module enriched for genes implicated in the pregnancy pathology preeclampsia. By using an independnet transcriptome dataset, we show that these co-expressed genes are differentially expressed in preeclampsia. Conclusions: This study represents a comprehensive characterisation of placental co-expression and provides insight into potential transcriptional regulators that govern conserved molecular programs fundamental to placental development.
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2017 |
Cuffe JSM, Saif Z, Perkins AV, Moritz KM, Clifton VL, 'Dexamethasone and sex regulate placental glucocorticoid receptor isoforms in mice', Journal of Endocrinology, 234 89-100 (2017)
Maternal dexamethasone exposure in the mouse impairs placental development and programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to different glucocortic... [more]
Maternal dexamethasone exposure in the mouse impairs placental development and programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to different glucocorticoid receptor (GR) isoforms to regulate gene transcription and cellular signaling. We hypothesized that sexually dimorphic placental responses to glucocorticoids are due to differences in GR isoforms present in the placenta. Pregnant C57Bl6 mice were exposed to saline or dexamethasone from E12.5 until E14.5 (1 µg/kg/h) before the collection of placentae. Cytoplasmic and nuclear protein fractions were extracted from placentae of male and female fetuses for Western blot analysis of GR isoforms. Eight known isoforms of the GR were detected in the mouse placenta including the translational isoforms GRa-A, B, C and D1-3 and the splice variants GRA and GRP. The expression of GRA, GRP and each of the GRa isoforms were altered by dexamethasone in relation to fetal sex and cellular location. Placentae of female fetuses had higher GRa-A and GRP expression in the cytoplasm than males, and GRa-C was more highly expressed in the nucleus of females than that in males. Dexamethasone significantly increased the cytoplasmic expression of GRa-A, but reduced the expression of GRa-C in placentae of males. Dexamethasone increased the expression of the GRa-C-regulated genes Sgk1 and Bcl2l11, particularly in females. The cleaved caspase-3 staining in placental sections indicated GRa-C may mediate sex differences in dexamethasone-induced apoptosis. These findings may underlie the sex-specific placental adaptations that regulate different growth profiles in males and females and different risks for programmed disease outcomes in offspring.
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2017 |
Grzeskowiak LE, Clifton VL, 'Authors' reply re: Antidepressant use in late gestation and risk of postpartum haemorrhage: a retrospective cohort study', BJOG: An International Journal of Obstetrics and Gynaecology, 124 1284-1285 (2017)
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2017 |
Grzeskowiak LE, Smith B, Roy A, Schubert KO, Baune BT, Dekker GA, Clifton VL, 'Impact of a history of maternal depression and anxiety on asthma control during pregnancy', Journal of Asthma, 54 706-713 (2017)
Objective: To determine the impact of self-reported maternal depression/anxiety on asthma control during pregnancy. Method: Pregnant women with a doctor diagnosis of asthma (n = 1... [more]
Objective: To determine the impact of self-reported maternal depression/anxiety on asthma control during pregnancy. Method: Pregnant women with a doctor diagnosis of asthma (n = 189) were prospectively recruited at their antenatal booking visit, and the presence of maternal depression and anxiety was identified using self-report and routine questionnaire assessments. Data on exacerbations and asthma control were collected during gestation. Asthma control was assessed using the Juniper Asthma Control Questionnaire (ACQ) and women were classified as having recurrent uncontrolled asthma if their ACQ score was >1.5 during two or more consecutive study visits. Exacerbations were defined as events that led to increased treatment requirements, and doctor or hospital visits. Results: There were 85 women with self-reported depression/anxiety and 104 women without self-reported depression/anxiety. The presence of depression/anxiety was associated with an increased likelihood (adjusted hazard ratio (HR) 1.67: 95% confidence interval (CI) 1.03¿2.72) and incidence (adjusted incidence rate ratio (IRR) 1.71: 95% CI 1.13¿2.58) of uncontrolled asthma during pregnancy, as well as an increased risk of recurrent uncontrolled asthma during 2 or more study visits (adjusted relative risk (RR) 1.98: 95% CI 1.00¿3.91). No impact of depression/anxiety was observed with respect to the likelihood (adjusted HR 0.70: 95% CI 0.35¿1.41) or incidence of exacerbations during pregnancy (adjusted IRR 0.66: 95% CI 0.35¿1.26). Conclusions: This study provides evidence that the presence of maternal depression/anxiety is associated with an increased likelihood and incidence of uncontrolled asthma during pregnancy. Given the high prevalence of co-morbid depression/anxiety among asthmatics, further research investigating such associations is urgently required.
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2017 |
Leggett C, Costi L, Morrison JL, Clifton VL, Grzeskowiak LE, 'Antidepressant Use in Late Gestation and Breastfeeding Rates at Discharge from Hospital', Journal of Human Lactation, 33 701-709 (2017)
Background: Few studies have investigated breastfeeding outcomes among women exposed to antidepressants. Research aim: This study aimed to evaluate the association between antidep... [more]
Background: Few studies have investigated breastfeeding outcomes among women exposed to antidepressants. Research aim: This study aimed to evaluate the association between antidepressant use in late gestation and maternal psychiatric illness on breastfeeding rates at discharge from hospital. Methods: The authors conducted a retrospective cohort study of 32,662 women delivering live-born singletons between January 2001 and December 2008. Electronic hospital records were used to obtain data on antidepressant exposure during late gestation and whether mothers were breastfeeding at discharge from hospital following delivery. Results: Five hundred seventy-five women received a dispensing for an antidepressant in late gestation (exposed), 1,552 did not receive a dispensing for an antidepressant but had a reported psychiatric illness (disease comparison), and 30,535 served as nonexposed controls. Exposed women were significantly less likely to be breastfeeding their infants at discharge from hospital compared with nonexposed women, adjusted odds ratio (AOR) = 0.63, 95% confidence interval (CI) [0.50-0.80], but no statistically significant difference was observed when compared with women in the disease comparison group, AOR = 0.83, 95% CI [0.65-1.07]. In stratified analyses, compared with women in the disease comparison group, exposed women were significantly less likely to be breastfeeding their infants at discharge from hospital if their neonate was delivered at term, AOR = 0.73, 95% CI [0.55-0.98], but not preterm, AOR = 1.24, 95% CI [0.66-2.32]. Conclusion: While antidepressant use is associated with a reduction in breastfeeding rates, this association appears to be strongly influenced by factors such as underlying maternal psychiatric illness. Overall, these results highlight that these women may benefit from additional education and support to improve breastfeeding rates.
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2017 |
Hodyl NA, Aboustate N, Bianco-Miotto T, Roberts CT, Clifton VL, Stark MJ, 'Child neurodevelopmental outcomes following preterm and term birth: What can the placenta tell us?', PLACENTA, 57 79-86 (2017)
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2016 |
Wright IMR, Latter JL, Dyson RM, Levi CR, Clifton VL, 'Videomicroscopy as a tool for investigation of the microcirculation in the newborn', PHYSIOLOGICAL REPORTS, 4 (2016) [C1]
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Nova |
2016 |
Vannuccini S, Lazzeri L, Orlandini C, Tosti C, Clifton VL, Petraglia F, 'Potential influence of in utero and early neonatal exposures on the later development of endometriosis', Fertility and Sterility, 105 997-1002 (2016)
Objective To investigate the possible correlation between maternal characteristics, in utero and early neonatal life exposures, and the development of endometriosis in adult life.... [more]
Objective To investigate the possible correlation between maternal characteristics, in utero and early neonatal life exposures, and the development of endometriosis in adult life. Design Case-control study. Setting University hospital. Patient(s) A group of 161 patients with endometriosis and a control group of 230 women undergoing laparoscopy for benign adnexal diseases and free of endometriosis. Intervention(s) All women included in the study were requested to answer a series of questions about their mothers' gestational data and on their own perinatal and early postnatal lives. Main Outcome Measure(s) Odds ratio, adjusted odds ratios, and 95% confidence intervals for the associations between maternal characteristics during the patient's pregnancy, in utero exposure to obstetrical and perinatal complications, and the type of feeding received during the neonatal period with the development of endometriosis in adult life. Result(s) Mothers of women with endometriosis were significantly more likely to be affected by endometriosis or uterine fibroids, with a higher incidence of smoking during pregnancy. Women with endometriosis were more frequently born prematurely, with a significantly lower birth weight, and their mothers experienced preeclampsia during their pregnancies more often than control subjects. They were also more frequently formula fed than breast fed in early life. However, only prematurity and formula feeding were retained in the multivariate analysis model. Conclusion(s) Among intrauterine and early neonatal exposures, prematurity and formula feeding were risk factors for the development of endometriosis in adult life. Further studies should evaluate the underlying biologic mechanisms.
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Nova |
2016 |
Clifton VL, Moss TJM, Wooldridge AL, Gatford KL, Liravi B, Kim D, et al., 'Development of an experimental model of maternal allergic asthma during pregnancy', Journal of Physiology, 594 1311-1325 (2016)
Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an ap... [more]
Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Maternal lung, fetal and placental phenotypes were characterised at 140 ± 1 days gestational age (term, ~147 days). The eosinophil influx into lungs was greater after HDM challenge in allergic ewes than after saline challenge in control ewes before mating and in late gestation. Airway resistance increased throughout pregnancy in allergic but not control ewes, consistent with increased airway smooth muscle in allergic ewes. Maternal allergic asthma decreased relative fetal weight (-12%) and altered placental phenotype to a more mature form. Expression of surfactant protein B mRNA was 48% lower in fetuses from allergic ewes than controls, with a similar trend for surfactant protein D. Thus, allergic asthma in pregnant sheep modifies placental phenotype, and inhibits fetal growth and lung development consistent with observations from human pregnancies. Preconceptional allergen sensitisation and repeated airway challenges in pregnant sheep therefore provides an animal model to identify mechanisms of altered fetal development and adverse pregnancy outcomes caused by maternal asthma in pregnancy.
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Nova |
2016 |
Sadovsky Y, Clifton VL, Knöfler M, 'Editorial: ZIKA virus and placenta', Placenta, 40 A1 (2016)
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2016 |
Grzeskowiak LE, Smith B, Roy A, Dekker GA, Clifton VL, 'An observational study of the impact of an antenatal asthma management service on asthma control during pregnancy', European Journal of Obstetrics and Gynecology and Reproductive Biology, 197 48-53 (2016)
Objective We sought to investigate the impact of introducing an antenatal asthma management service (AMS) on asthma control during pregnancy and subsequent perinatal outcomes. Stu... [more]
Objective We sought to investigate the impact of introducing an antenatal asthma management service (AMS) on asthma control during pregnancy and subsequent perinatal outcomes. Study design Prospective, observational cohort study of pregnant asthmatic women attending a tertiary hospital antenatal clinic. Asthmatic women were recruited from the antenatal clinic and were followed prospectively with visits at 12, 20, 28 and 36 weeks gestation. A new nurse-led AMS was introduced offering asthma self-management education and support. Outcomes were compared between women recruited before and after the AMS was introduced (n = 89 and 80, respectively) and included; prevalence of exacerbations during pregnancy, asthma control throughout pregnancy and perinatal outcomes, including preterm birth and small-for-gestational-age (SGA). Results The relative risk for exacerbations (0.69; CI: 0.33-1.42), loss of control (0.67; CI 0.46-0.99) and persistent uncontrolled asthma (0.48; CI 0.26-0.9) were all reduced with attendance to AMS during pregnancy. AMS was associated with non-statistically significant reductions in asthma exacerbations (19.1-15.0%; p = 0.480) and uncontrolled asthma at =2 study visits (21.3-11.3%; p = 0.078). Conclusions These findings demonstrate the potential impact of an AMS in improving asthma control during pregnancy, supporting the need for an adequately powered RCT to determine its clinical- and cost-effectiveness.
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Nova |
2016 |
McBain RD, Dekker GA, Clifton VL, Mol BW, Grzeskowiak LE, 'Impact of inter-pregnancy BMI change on perinatal outcomes: a retrospective cohort study', European Journal of Obstetrics and Gynecology and Reproductive Biology, 205 98-104 (2016)
Objective To examine the patterns and predictors of inter-pregnancy body mass index (BMI) change and its impact on perinatal outcomes in the second pregnancy. Design Retrospective... [more]
Objective To examine the patterns and predictors of inter-pregnancy body mass index (BMI) change and its impact on perinatal outcomes in the second pregnancy. Design Retrospective cohort study. Setting Tertiary teaching hospital in Adelaide, Australia. Population Women with their first and second consecutive, singleton deliveries occurring between 2000 and 2012 (N¿=¿5371). Methods Inter-pregnancy weight change calculated based on difference between BMI at respective antenatal booking visits. Association between inter-pregnancy weight change and perinatal outcomes investigated using multivariate generalised linear models, with stratification according to initial maternal BMI category in first pregnancy. Main outcome measures Gestational diabetes (GDM); pregnancy induced hypertensive disorders; small-for-gestational age (SGA); preterm birth; large-for-gestational age (LGA) and macrosomia (>4500¿g). Results On average, women with a normal BMI gained 1¿kg/m 2 between first and second pregnancies, while women who were overweight or obese gained 1.37¿kg/m 2 . Among women with a normal BMI in their first pregnancy, a BMI increase of =4¿kg/m 2 was associated with increased risk of developing GDM (aRR 1.97; 95% CI 1.22¿3.19), a macrosomic (aRR 4.06; 95% CI 2.25¿7.34) or LGA infant (aRR 1.31 0.96¿1.78) in the second pregnancy, while a reduction in BMI (=¿2¿kg/m 2 ) was associated with an increased risk of SGA (aRR 1.94; 1.19¿3.16). Among women who were overweight or obese in their first pregnancy, a BMI increase of =2¿4 and =4¿kg/m 2 was associated with increased risks of developing GDM in the second pregnancy (aRR 1.39; 95% CI 1.01¿1.91 and aRR 1.64 95% CI 1.16¿2.31; p trend ¿<¿0.001), while no associations were observed for a BMI increase and risk of a macrosomic, SGA, or LGA infant. In contrast, reduction in BMI (=¿2¿kg/m 2 ) was associated with a reduced risk of GDM (aRR 0.58 95% CI 0.37¿0.90) and SGA (aRR 0.47; 95% CI 0.25¿0.87). Conclusion Increases in BMI between pregnancies is associated with an increased risk for perinatal complications, even in normal-weight women, while a reduction in BMI is associated with improved perinatal outcomes among women who are overweight/obese. Inter-pregnancy weight control is an important target to reduce the risk of an adverse perinatal outcome in a subsequent pregnancy.
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Nova |
2016 |
Grieger JA, Clifton VL, Tuck AR, Wooldridge AL, Robertson SA, Gatford KL, 'In utero Programming of Allergic Susceptibility', International Archives of Allergy and Immunology, 169 80-92 (2016)
Background: Around 30-40% of the world's population will experience allergy, the most common and earliest-onset noncommunicable disease. With a steady rise in the incidence o... [more]
Background: Around 30-40% of the world's population will experience allergy, the most common and earliest-onset noncommunicable disease. With a steady rise in the incidence of allergic disease over recent decades, up to 18% of children will suffer a respiratory, food or skin allergy before their 18th birthday. There is compelling evidence that the risk of developing allergy is influenced by early life events and particularly in utero exposures. Methods: A comprehensive literature review was undertaken which outlines prenatal risk factors and potential mechanisms underlying the development of allergy in childhood. Results: Exposures including maternal cigarette smoking, preterm birth and Caesarean delivery are implicated in predisposing infants to the later development of allergy. In contrast, restricted growth in utero, a healthy maternal diet and a larger family size are protective, but the mechanisms here are unclear and require further investigation. Conclusion: To ameliorate the allergy pandemic in young children, we must define prenatal mechanisms that alter the programming of the fetal immune system and also identify specific targets for antenatal interventions.
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Nova |
2016 |
Vannuccini S, Clifton VL, Fraser IS, Taylor HS, Critchley H, Giudice LC, Petraglia F, 'Infertility and reproductive disorders: Impact of hormonal and inflammatory mechanisms on pregnancy outcome', Human Reproduction Update, 22 104-115 (2016)
Background: Reproductive disorders and infertility are associated with the risk of obstetric complications and have a negative impact on pregnancy outcome. Affected patients often... [more]
Background: Reproductive disorders and infertility are associated with the risk of obstetric complications and have a negative impact on pregnancy outcome. Affected patients often require assisted reproductive technologies (ART) to conceive, and advanced maternal age is a further confounding factor. The challenge is to dissect causation, correlation and confounders in determining how infertility and reproductive disorders individually or together predispose women to poor pregnancy outcomes. methods: The published literature, to June 2015, was searched using PubMed, summarizing all evidences concerning the perinatal outcome of women with infertility and reproductive disorders and the potential mechanisms that may influence poor pregnancy outcome. Results: Reproductive disorders (endometriosis, adenomyosis, polycystic ovary syndrome and uterine fibroids) and unexplained infertility share inflammatory pathways, hormonal aberrations, decidual senescence and vascular abnormalities that may impair pregnancy success through common mechanisms. Either in combination or alone, these disorders results in an increased risk of preterm birth, fetal growth restriction, placental pathologies and hypertensive disorders. Systemic hormonal aberrations, and inflammatory and metabolic factors acting on endometrium, myometrium, cervix and placenta are all associated with an aberrant milieu during implantation and pregnancy, thus contributing to the genesis of obstetric complications. Some of these features have been also described in placentas from ART. Conclusions: Reproductive disorders arecommoninwomenof childbearing age and rarely occur in isolation. Inflammatory, endocrine and metabolic mechanisms associated with these disorders are responsible for an increased incidence of obstetric complications. These patients should be recognized as 'high risk' for poor pregnancy outcomes and monitored with specialized follow-up. There is a real need for development of evidence-based recommendations about clinical management and specific obstetric care pathways for the introduction of prompt preventative care measures.
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Nova |
2016 |
Grzeskowiak LE, McBain R, Dekker GA, Clifton VL, 'Antidepressant use in late gestation and risk of postpartum haemorrhage: a retrospective cohort study', BJOG: An International Journal of Obstetrics and Gynaecology, 123 1929-1936 (2016)
Objective: To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH). Design: Retrospective cohort study. Setting: Tertiary teac... [more]
Objective: To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH). Design: Retrospective cohort study. Setting: Tertiary teaching hospital in Adelaide, Australia. Population: A total of 30¿198 women delivering between 2002 and 2008. Methods: Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n¿=¿558), women with a psychiatric illness but no antidepressant use (n¿=¿1292), and women with neither antenatal exposures (n¿=¿28¿348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia. Main outcome measures: The primary outcome was PPH, defined as a recorded blood loss of =500¿mL for vaginal deliveries and =1000¿mL for caesarean sections. Secondary outcomes included severe PPH (=1000¿mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records). Results: Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR¿1.53; 95% confidence interval, 95%¿CI 1.25¿1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR¿1.04; 95%¿CI 0.89¿1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR¿1.84; 95%¿CI 1.39¿2.44), as well as postpartum anaemia (aRR¿1.80; 95%¿CI¿1.46¿2.22). Conclusions: Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH. Tweetable abstract: Late gestation antidepressant exposure is associated with a significantly increased risk of postpartum haemorrhage.
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Nova |
2016 |
Dickinson H, Davies-Tuck M, Ellery SJ, Grieger JA, Wallace EM, Snow RJ, et al., 'Maternal creatine in pregnancy: a retrospective cohort study', BJOG: An International Journal of Obstetrics and Gynaecology, 123 1830-1838 (2016)
Objective: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. Design: Retrospectiv... [more]
Objective: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. Design: Retrospective cohort study. Setting: Lyell McEwin Hospital, Adelaide, Australia. Population: A biobank of plasma and urine samples collected at 13, 18, 30 and 36¿weeks¿ gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. Methods: Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. Main outcome measures: Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. Results: Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each µmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44¿2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03¿0.2) increase in birth length. Conclusions: Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. Tweetable abstract: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations.
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Nova |
2016 |
Saif Z, Dyson RM, Palliser HK, Wright IMR, Lu N, Clifton VL, 'Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure', PLOS ONE, 11 (2016) [C1]
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Nova |
2016 |
Grzeskowiak LE, Smith B, Roy A, Dekker GA, Clifton VL, 'Patterns, predictors and outcomes of asthma control and exacerbations during pregnancy: A prospective cohort study', ERS Monograph, 2 (2016)
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Nova |
2016 |
Grieger JA, Grzeskowiak LE, Wood LG, Clifton VL, 'Asthma control in pregnancy is associated with pre-conception dietary patterns', Public Health Nutrition, 19 332-338 (2016) [C1]
Objective To examine pre-conception dietary patterns in pregnant asthmatic women and to identify associations between maternal diet and asthma control during pregnancy. Design Cro... [more]
Objective To examine pre-conception dietary patterns in pregnant asthmatic women and to identify associations between maternal diet and asthma control during pregnancy. Design Cross-sectional study. Pre-conception food frequency data were collected retrospectively. Asthma control was assessed using the Global Initiative for Asthma guidelines. Dietary patterns were derived using factor analysis. Binary logistic regression analyses were used to test the association between uncontrolled asthma and each dietary pattern (Z-score), with values presented as odds ratio and 95 % confidence interval. Setting Antenatal clinic in a tertiary hospital, Adelaide, Australia, May 2009-July 2013. Subjects One hundred and fifty-eight asthmatic pregnant women. Results Three dietary patterns were identified: (i) 'high protein/fruit' (strong food group loadings for fish, meat, chicken, fruit); (ii) 'high fat/sugar/takeaway' (takeaway foods, crisps, refined grains); and (iii) 'vegetarian-type' (vegetables, fruit, soya milk, whole grains). A 1 sd increase in score on the high fat/sugar/takeaway pattern was associated with increased likelihood of uncontrolled asthma (adjusted OR=1·54; 95 % CI 1·07, 2·23; P=0·022). Women with uncontrolled asthma (n 115) had higher energy-adjusted intakes of saturated fat, monounsaturated fat, carbohydrate, sugar and fibre compared with women with controlled asthma (n 43, all P=0·05). Conclusions Pre-pregnancy dietary patterns may influence maternal asthma control. Our work highlights the importance of achieving a healthy diet before pregnancy that is low in saturated fat, sugar and takeaway foods, and therefore higher in lean meats, poultry and fish, as well as fruits, vegetables and whole grains. A healthy dietary pattern should be encouraged in all asthmatic women who are of childbearing age, and should additionally be promoted before pregnancy and beyond.
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Nova |
2016 |
Mayne BT, Bianco-Miotto T, Buckberry S, Breen J, Clifton V, Shoubridge C, Roberts CT, 'Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans', Frontiers in Genetics, 7 (2016)
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Nova |
2016 |
Tucker J, Wilson A, Clifton VL, 'IMPROVING COMMUNICATION AROUND ANAL INCONTINENCE FOR WOMEN OF REPRODUCTIVE AGE', Australian nursing & midwifery journal, 24 37 (2016)
Anal incontinence (AI) is the accidental loss of liquid or solid stool and flatus (Milsom et al. 2009). The concept of uncontrolled faecal loss can evoke social disgust and margin... [more]
Anal incontinence (AI) is the accidental loss of liquid or solid stool and flatus (Milsom et al. 2009). The concept of uncontrolled faecal loss can evoke social disgust and marginalize those afflicted from the community in which they live (Williams et al. 2005).
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2016 |
Wittwer M, Chow YY, Dekker G, Clifton V, Arstall M, 'F5. Skin microvascular dysfunction in preeclampsia persists to the postpartum period', Journal of Maternal-Fetal and Neonatal Medicine, 29 30 (2016)
Introduction: Preeclampsia is a multisystem disorder characterised by endothelial and microvascular dysfunction that develops in ~10% of pregnancies. This study will characterise ... [more]
Introduction: Preeclampsia is a multisystem disorder characterised by endothelial and microvascular dysfunction that develops in ~10% of pregnancies. This study will characterise skin microvascular reactivity using laser Doppler flowmetry in women with preeclampsia compared to matched controls during pregnancy and early postpartum. Methods: Women were recruited and studied on the diagnosis of preeclampsia and followed up for 6-months during postpartum period. Controls were matched for age, gestation and comorbidities. Skin blood flow corrected for mean arterial pressure (cutaneous vascular conductance; CVC) was measured using laser Doppler flowmetry (Periflux5000, Perimed AB, Sweden) on the dominant forearm. We measured the vasodilatory response to iontophoresis of acetylcholine (ACh; endothelial dependent) and sodium nitroprusside (SNP; endothelial independent) as well as local heating (initial axon-reflex and secondary nitric oxide-mediated). Results were analysed using repeated measures ANOVA. Results: Fourteen women with preeclampsia and 15 controls were included in this analysis. Compared to controls, women with preeclampsia had significantly decreased baseline CVC during pregnancy, which persisted to the postpartum (p < 0.01). There was a significant increase in the ratio of maximum vasodilatory response to ACh and SNP at both time points (p < 0.01). There was a trend towards a higher initial axon-reflex response to heat (p = 0.05), but no difference in the secondary peak response. Conclusions: This study is the first to demonstrate a significantly increased response to ACh compared to SNP during pregnancy that persisted in the postpartum period. In addition, we demonstrated that the response to heat may not recover in the early postpartum period. These findings indicate persistent microvascular dysfunction in women with preeclampsia.
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2016 |
Corbisier De Meautsart C, Dyson RM, Latter JL, Berry MJ, Clifton VL, Wright IMR, 'Influence of sympathetic activity in the control of peripheral microvascular tone in preterm infants', Pediatric Research, 80 793-799 (2016) [C1]
Background:Microvascular dysregulation following preterm birth is associated with increased illness severity and hypotension, particularly in males. Sympathetic nervous vascular r... [more]
Background:Microvascular dysregulation following preterm birth is associated with increased illness severity and hypotension, particularly in males. Sympathetic nervous vascular regulation is evident in females. We hypothesized that sympathetic dysfunction in male preterm infants may contribute to a failure of peripheral microvascular vasoconstriction.Methods:Microvascular blood flow of infants 24-43 wk gestational age was assessed at 6, 24, and 72 h of age by laser Doppler. Blood flow Fourier transformed frequency distribution spectra (low frequency/high frequency ratio) were used to assess the influence of sympathetic tone on microvascular regulation. Total sympathetic output was assessed as urinary normetanephrine.Results:Microvascular sympathetic activity at 24 h postnatal age decreased in early preterm males, but not females. Peripheral sympathetic activity increased with advancing postnatal age in females, but decreased in males. In early preterm infants, total normetanephrine outputs increase significantly with postnatal age, in both sexes.Conclusion:Sympathetic activation following preterm birth is sexually dimorphic, with preterm males having reduced sympathetic tone and reduced upregulation of sympathetic tone following birth. There is evidence of a disconnect between central sympathetic activity and local peripheral microcirculatory sympathetic drive. This may relate to autonomic nervous immaturity and highlights the need to understand how preterm birth may affect autonomic function.
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Nova |
2016 |
Albrecht C, Caniggia I, Clifton V, Gohner C, Harris L, Hemmings D, et al., 'IFPA meeting 2015 workshop report III: nanomedicine applications and exosome biology, xenobiotics and endocrine disruptors and pregnancy, and lipid', PLACENTA, 48 S12-S16 (2016)
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2015 |
Saif Z, Hodyl NA, Stark MJ, Fuller PJ, Cole T, Lu N, Clifton VL, 'Expression of eight glucocorticoid receptor isoforms in the human preterm placenta vary with fetal sex and birthweight', Placenta, 36 723-730 (2015) [C1]
Introduction Administration of betamethasone to women at risk of preterm delivery is known to be associated with reduced fetal growth via alterations in placental function and pos... [more]
Introduction Administration of betamethasone to women at risk of preterm delivery is known to be associated with reduced fetal growth via alterations in placental function and possibly direct effects on the fetus. The placental glucocorticoid receptor (GR) is central to this response and recent evidence suggests there are numerous isoforms for GR in term placentae. In this study we have questioned whether GR isoform expression varies in preterm placentae in relation to betamethasone exposure, fetal sex and birthweight. Methods Preterm (24-36 completed weeks of gestation, n = 55) and term placentae (>37 completed weeks of gestation, n = 56) were collected at delivery. Placental GR expression was examined using Western Blot and analysed in relation to gestational age at delivery, fetal sex, birthweight and betamethasone exposure. Data was analysed using non-parametric tests. Results Eight known isoforms of the GR were detected in the preterm placenta and include GRa (94 kDa), GRß (91 kDa), GRa C (81 kDa) GR P (74 kDa) GR A (65 kDa), GRa D1-3 (50-55 kDa). Expression varied between preterm and term placentae with a greater expression of GRa C in preterm placentae relative to term placentae. The only sex differences in preterm placentae was that GRa D2 expression was higher in males than females. There were no alterations in preterm placental GR expression in association with betamethasone exposure. Discussion GRa C is the isoform involved in glucocorticoid induced apoptosis and suggests that its predominance in preterm placentae may contribute to the pathophysiology of preterm birth.
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2015 |
Wilmore M, Rodger D, Humphreys S, Clifton VL, Dalton J, Flabouris M, Skuse A, 'How midwives tailor health information used in antenatal care', Midwifery, 31 74-79 (2015) [C1]
Objective: to examine the informal approaches taken by midwives and other antenatal staff to adapt health communication to the needs of their patients, as well as their perception... [more]
Objective: to examine the informal approaches taken by midwives and other antenatal staff to adapt health communication to the needs of their patients, as well as their perception of the barriers faced when trying to provide tailored health promotion. Design: qualitative research methods (participant observation, individual and group interviews) were utilised to gain an understanding of how media and communication resources were used in practice within the study hospital. Setting: a major metropolitan teaching hospital located in the Northern suburbs of Adelaide, South Australia. Participants: individual semi-structured interviews with antenatal staff (n=8) were combined with group interviews (n=2; total number of staff=13), and observational research. Findings: midwives and other antenatal staff use a range of strategies to meet the perceived health literacy level of their patients. However, their attempts to tailor health information to individual needs are frequently based on incomplete information about patients' health literacy, may be inconsistent in delivery and content and are seldom assessed to determine whether communication has been understood or led to patient behaviour change. Key conclusions: midwives fully recognise the need to adapt standard printed materials to meet the diverse health literacy needs of patients but lack the resources required to evaluate whether these adaptations have positive effect. Implications for practice: midwives' commitment to improving health communication provides a latent resource that institutions can build on to improve health outcomes for patients with low health literacy. This requires improvements in health communication training, willingness to use a range of validated instruments for measuring health literacy, and commitment to use of innovative approaches to health promotion where these have been shown to have a positive impact on health behaviours.
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2015 |
Grzeskowiak LE, Clifton VL, 'Asthma management during pregnancy: How long before we can all breathe a little easier?', Journal of Asthma, 52 1020-1022 (2015)
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2015 |
Conti N, Torricelli M, Voltolini C, Vannuccini S, Clifton VL, Bloise E, Petraglia F, 'Term histologic chorioamnionitis: A heterogeneous condition', European Journal of Obstetrics and Gynecology and Reproductive Biology, 188 34-38 (2015)
Abstract A histologic response of histologic chorioamnionitis (HCA) is defined as an intrauterine inflammatory condition characterized by acute granulocyte infiltratration into th... [more]
Abstract A histologic response of histologic chorioamnionitis (HCA) is defined as an intrauterine inflammatory condition characterized by acute granulocyte infiltratration into the fetal-maternal or the fetal tissues. Prevalence of HCA is inversely correlated with gestational age, occurring in 50% of preterm birth and in up to 20% of deliveries at term. Regardless of these standard definitions, understanding HCA is challenging as it reflects a heterogeneous condition. A histologic response of HCA from term placentas often does not correspond to a clinical presentation; in this context, the present review aims to analyze main characteristics of this condition, in particular focusing on mechanisms and birth outcomes.
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2015 |
Grzeskowiak LE, Hodyl NA, Stark MJ, Morrison JL, Clifton VL, 'Association of early and late maternal smoking during pregnancy with offspring body mass index at 4 to 5 years of age', Journal of Developmental Origins of Health and Disease, 6 485-492 (2015)
The objective was to investigate the association between early and late maternal smoking during pregnancy on offspring body mass index (BMI). We undertook a retrospective cohort s... [more]
The objective was to investigate the association between early and late maternal smoking during pregnancy on offspring body mass index (BMI). We undertook a retrospective cohort study using linked records from the Women's and Children's Health Network in South Australia. Among a cohort of women delivering a singleton, live-born infants between January 2000 and December 2005 (n=7658), 5961 reported not smoking during pregnancy, 297 reported quitting smoking during the first trimester of pregnancy, and 1400 reported continued smoking throughout pregnancy. Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance programme. The main outcome measure was age- and sex-specific BMI z-score. At 4 to 5 years, mean (s.d.) BMI z-score was 0.40 (1.05), 0.60 (1.07) and 0.65 (1.18) in children of mothers who reported never smoking, quitting smoking and continued smoking during pregnancy, respectively. Compared with the group of non-smokers, both quitting smoking and continued smoking were associated with an increase in child BMI z-score of 0.15 (95% confidence interval: 0.01-0.29) and 0.21 (0.13-0.29), respectively. A significant dose-response relationship was also observed between the number of cigarettes smoked per day on average during the second half of pregnancy and the increase in offspring BMI z-score (P<0.001). In conclusion, any maternal smoking in pregnancy, even if mothers quit, is associated with an increase in offspring BMI at 4 to 5 years of age.
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2015 |
Grieger JA, Clifton VL, 'A review of the impact of dietary intakes in human pregnancy on infant birthweight', Nutrients, 7 153-178 (2015)
Studies assessing maternal dietary intakes and the relationship with birthweight are inconsistent, thus attempting to draw inferences on the role of maternal nutrition in determin... [more]
Studies assessing maternal dietary intakes and the relationship with birthweight are inconsistent, thus attempting to draw inferences on the role of maternal nutrition in determining the fetal growth trajectory is difficult. The aim of this review is to provide updated evidence from epidemiological and randomized controlled trials on the impact of dietary and supplemental intakes of omega-3 long-chain polyunsaturated fatty acids, zinc, folate, iron, calcium, and vitamin D, as well as dietary patterns, on infant birthweight. A comprehensive review of the literature was undertaken via the electronic databases Pubmed, Cochrane Library, and Medline. Included articles were those published in English, in scholarly journals, and which provided information about diet and nutrition during pregnancy and infant birthweight. There is insufficient evidence for omega-3 fatty acid supplements¿ ability to reduce risk of low birthweight (LBW), and more robust evidence from studies supplementing with zinc, calcium, and/or vitamin D needs to be established. Iron supplementation appears to increase birthweight, particularly when there are increases in maternal hemoglobin concentrations in the third trimester. There is limited evidence supporting the use of folic acid supplements to reduce the risk for LBW; however, supplementation may increase birthweight by ~130 g. Consumption of whole foods such as fruit, vegetables, low-fat dairy, and lean meats throughout pregnancy appears beneficial for appropriate birthweight. Intervention studies with an understanding of optimal dietary patterns may provide promising results for both maternal and perinatal health. Outcomes from these studies will help determine what sort of dietary advice could be promoted to women during pregnancy in order to promote the best health for themselves and their baby.
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2015 |
Zouikr I, Ahmed AF, Horvat JC, Beagley KW, Clifton VL, Ray A, et al., 'Programming of formalin-induced nociception by neonatal LPS exposure: Maintenance by peripheral and central neuroimmune activity', Brain, Behavior, and Immunity, 44 235-246 (2015) [C1]
The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of develop... [more]
The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of development are known to produce long-lasting effects on the immune and nociceptive responses. It is less clear, however, whether inflammatory pain responses are primed by neonatal exposure to mild immunological stimuli, such as with lipopolysaccharide (LPS). Here, we examine the impact of neonatal LPS exposure on inflammatory pain responses, peripheral and hippocampal interleukin-1ß (IL-1ß), as well as mast cell number and degranulation in preadolescent and adult rats. Wistar rats were injected with LPS (0.05 mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 22 and 80-97. At both time-points, and one-hour after formalin injection, blood and hippocampus were collected for measuring circulating and central IL-1ß levels using ELISA and Western blot, respectively. Paw tissue was also isolated to assess mast cell number and degree of degranulation using Toluidine Blue staining. Behavioural analyses indicate that at PND 22, LPS-challenged rats displayed enhanced flinching (p<.01) and licking (p<.01) in response to formalin injection. At PNDs 80-97, LPS-challenged rats exhibited increased flinching (p<.05), an effect observed in males only. Furthermore, neonatal LPS exposure enhanced circulating IL-1ß and mast cell degranulation in preadolescent but not adult rats following formalin injection. Hippocampal IL-1ß levels were increased in LPS-treated adult but not preadolescent rats in response to formalin injection. These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, peripheral and central IL-1ß levels, as well as mast cell degranulation following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping immune response and pain sensitivity later in life. This is of clinical relevance given the high prevalence of bacterial infection during the neonatal period, particularly in the vulnerable population of preterm infants admitted to neonatal intensive care units.
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Nova |
2015 |
Powell H, Murphy VE, Hensley MJ, Giles W, Clifton VL, Gibson PG, 'Rhinitis in pregnant women with asthma is associated with poorer asthma control and quality of life', Journal of Asthma, (2015) [C1]
© 2015 Taylor & Francis. Objective: To describe the pattern and severity of rhinitis in pregnancy and the impact rhinitis has on asthma control and quality of life (QoL) in pr... [more]
© 2015 Taylor & Francis. Objective: To describe the pattern and severity of rhinitis in pregnancy and the impact rhinitis has on asthma control and quality of life (QoL) in pregnant women with asthma. Methods: Two hundred and eighteen non-smoking pregnant women with asthma were participants in a randomised controlled trial of exhaled nitric oxide guided treatment adjustment. Rhinitis was assessed using a visual analogue scale (VAS) scored from 0 to 10 and classified as current (VAS¿>¿2.5), moderate/severe versus mild (VAS¿>¿6 vs <5), atopic versus non-atopic and pregnancy rhinitis. At baseline, women completed the 20-Item Sino-Nasal Outcome Test (SNOT20), asthma-specific (AQLQ-M) QoL questionnaires and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Asthma control was assessed using the asthma control questionnaire (ACQ). Perinatal outcomes were collected after delivery. Results: Current rhinitis was present in 142 (65%) women including 45 (20%) women who developed pregnancy rhinitis. Women with current rhinitis had higher scores for ACQ (p¿=¿0.004), SNOT20 (p¿<¿0.0001) and AQLQ-M (p¿<¿0.0001) compared to women with no rhinitis. Current rhinitis was associated with increased anxiety symptoms (p¿=¿0.002), rhinitis severity was associated with higher ACQ score (p¿=¿0.004) and atopic rhinitis was associated with poorer lung function (p¿=¿0.037). Rhinitis symptom severity improved significantly during gestation (p¿<¿0.0001). There was no impact on perinatal outcomes. Improved asthma control was associated with improvement in rhinitis. Conclusion: Rhinitis in pregnant women with asthma is common and associated with poorer asthma control, sino-nasal and asthma-specific QoL impairment and anxiety. In the context of active asthma management there was significant improvement in rhinitis symptoms and severity as pregnancy progressed.
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Nova |
2014 |
Dyson RM, Palliser HK, Lakkundi A, de Waal K, Latter JL, Clifton VL, Wright IMR, 'Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig.', Physiol Rep, 2 (2014) [C1]
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Nova |
2014 |
Grieger JA, Wood LG, Clifton VL, 'Antioxidant-rich dietary intervention for improving asthma control in pregnancies complicated by asthma: Study protocol for a randomized controlled trial', Trials, 15 (2014) [C3]
Background: Asthma is the most prevalent chronic disease to complicate pregnancies worldwide, affecting around 12% of pregnant women in Australia. Oxidative stress and inflammatio... [more]
Background: Asthma is the most prevalent chronic disease to complicate pregnancies worldwide, affecting around 12% of pregnant women in Australia. Oxidative stress and inflammation manifest during pregnancy; however asthma in pregnancies further intensifies oxidative stress. Consumption of antioxidant-rich foods has been shown to be beneficial for asthma control in non-pregnant asthmatic adults. It has not been investigated whether antioxidant-rich foods can improve the elevated oxidative stress that occurs with asthma in pregnancy, thereby improving asthma control. The primary aim of this study is to determine whether increased consumption of antioxidant-rich foods for 12 weeks will improve maternal asthma control, compared to standard dietary intake during pregnancy.Methods/design: A 12 week, parallel randomized controlled trial will be conducted. One hundred and sixty eight pregnant women with mild, moderate, or severe asthma, currently using inhaled corticosteroids, and with poor diet quality, will be recruited at approximately12 weeks gestation. Following a 4 week run-in period, women will be randomized to either a 12 week antioxidant intervention (increased consumption of antioxidant-rich foods (=5 servings/day vegetables, =2 servings/day fruit, =8 1-Feb servings/day grains (mostly wholegrains), 3-4 serving/week lean meat) or standard pregnancy care. The primary outcome is asthma control score (decrease of 0.5, the minimally clinically significant change). Secondary outcomes include plasma antioxidants, markers of oxidative stress, and time to, and number of, exacerbations. With two-tailed t-tests at 80% power, a sample size of 52 completions per group is required. Allowing for a 78% retention including a 20% removal of women from the analysis due to non-compliance, we will recruit 168 women.Discussion: It is expected that this 12 week study will improve asthma control. This is significant because asthma is the most prevalent condition to complicate pregnancies and contributes to poor maternal, neonatal and infant health outcomes. Our research will provide the first evidence to show that, in pregnancy, consumption of antioxidant-rich foods is a key modifier of clinical asthma status. This research is crucial for contributing to the evidence base to inform future guidelines given existing clinical and research gaps.Trial registration: ACTRN12613000301763. © 2014 Grieger et al.; licensee BioMed Central Ltd.
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Nova |
2014 |
Zouikr I, Tadros MA, Barouei J, Beagley KW, Clifton VL, Callister RJ, Hodgson DM, 'Altered nociceptive, endocrine, and dorsal horn neuron responses in rats following a neonatal immune challenge', PSYCHONEUROENDOCRINOLOGY, 41 1-12 (2014) [C1]
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Nova |
2014 |
Zouikr I, James MH, Campbell EJ, Clifton VL, Beagley KW, Dayas CV, Hodgson DM, 'Altered formalin-induced pain and fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure', PLoS ONE, 9 (2014) [C1]
Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanic... [more]
Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supraspinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process. © 2014 Zouikr et al.
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Nova |
2014 |
Tucker J, Clifton V, Wilson A, 'Teetering near the edge; Women's experiences of anal incontinence following obstetric anal sphincter injury: An interpretive phenomenological research study', Australian and New Zealand Journal of Obstetrics and Gynaecology, 54 377-381 (2014)
Background Obstetric anal sphincter injury (OASIS) following vaginal delivery increases the risk of anal incontinence (AI). Subsequent vaginal delivery and ageing increase the ris... [more]
Background Obstetric anal sphincter injury (OASIS) following vaginal delivery increases the risk of anal incontinence (AI). Subsequent vaginal delivery and ageing increase the risk of worsening symptoms. Very little literature describes any in-depth understanding of what it is like to live with AI following a history of known OASIS. Aim To describe and interpret women's experience of AI following OASIS and its impact on quality of life. Methods An interpretive phenomenological study was conducted in a level 2 tertiary hospital in South Australia. Women with a history of OASIS and AI were purposefully recruited. The St Marks Vaizey score was utilised to identify symptom severity. Semi-structured open-ended interviews were conducted, and data were analysed utilising Van Manen thematic analysis. Results Participants (n = 10) aged 26-56 years. All women were symptomatic of AI following OASIS, and 80% had received a primary OASIS at their first vaginal delivery. The St Marks Vaizey score mean was 9.1 (range within 4-22). Three essential themes grieving for loss, silence, striving for normality with eight subthemes identified a significant sense of loss and psychological impact of AI for this group of women. Conclusion Health professionals require a greater understanding of the negative impact of OASIS and AI on women's quality of life. This may improve the management, education and clinical care of this condition which may result as a consequence of OASIS. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.
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2014 |
Grieger JA, Grzeskowiak LE, Clifton VL, 'Preconception dietary patterns in human pregnancies are associated with preterm delivery', Journal of Nutrition, 144 1075-1080 (2014) [C1]
Maternal nutrition can have a profound effect on fetal growth, development, and subsequent infant birth weight. Preconception dietary patterns have not been assessed in relation t... [more]
Maternal nutrition can have a profound effect on fetal growth, development, and subsequent infant birth weight. Preconception dietary patterns have not been assessed in relation to perinatal outcomes. The objectives of this study were to identify associations between maternal dietary patterns in the 12 mo before conception on fetal growth and preterm delivery. Preconception food frequency data were collected retrospectively in 309 women. Dietary patterns were derived using factor analysis. Perinatal outcomes were collected at delivery with birth weight data calculated into percentiles to assess small and large for gestational age and preterm delivery at <37 wk. Three dietary patterns were identified: 1) high-protein/fruit (characterized by fish, meat, chicken, fruit, and some whole grains); 2) high-fat/sugar/ takeaway (takeaway foods, potato chips, refined grains); and 3) vegetarian-type (vegetables, legumes, whole grains). A 1-SD increase in the scores on the high-protein/fruit pattern was associated with decreased likelihood of preterm birth (adjusted OR: 0.31; 95% CI: 0.13, 0.72; P = 0.007), whereas the reverse direction was apparent for the high-fat/sugar/takeaway pattern (adjusted OR: 1.54; 95% CI: 1.10, 2.15; P = 0.011). A 1-SD increase in the scores on the high fat/sugar/takeaway pattern was also associated with shorter gestation (adjusted regression coefficient: 22.7; 95% CI: 24.3, 21.1; P = 0.001) and birth length (adjusted regression coefficient: 20.5; 95% CI: 20.8, 20.1; P = 0.004). Nutrition before pregnancy is associated with perinatal outcomes. A dietary pattern containing several protein-rich food sources, fruit, and some whole grains is associated with reduced likelihood for preterm delivery, whereas a dietary pattern mainly consisting of discretionary items is associated with preterm delivery, shorter birth length, and earlier gestation. Poor dietary behaviors in the periconceptional period could be altered to promote behavior change in dietary intake to improve perinatal outcomes and the long-term health of the child. © 2014 American Society for Nutrition.
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2014 |
Hodyl NA, Grzeskowiak LE, Stark MJ, Scheil W, Clifton VL, 'The impact of Aboriginal status, cigarette smoking and smoking cessation on perinatal outcomes in South Australia', Medical Journal of Australia, 201 274-278 (2014) [C1]
Objective: To assess the impact of Aboriginal status, active cigarette smoking and smoking cessation during pregnancy on perinatal outcomes. Design: Retrospective cohort study fro... [more]
Objective: To assess the impact of Aboriginal status, active cigarette smoking and smoking cessation during pregnancy on perinatal outcomes. Design: Retrospective cohort study from 1 January 1999 to 31 December 2008. Setting: All singleton births in South Australia. Participants: Population-based birth records of pregnancies to Aboriginal women (n = 4245) and non-Aboriginal women (n = 167 746). Main outcome measures: Adjusted odds ratios (aORs) and 95% CIs for adverse maternal and neonatal outcomes according to Aboriginal status and maternal smoking in pregnancy. Results: Active cigarette smoking during pregnancy was associated with an increased risk of adverse perinatal outcomes, including premature labour (Aboriginal, 1-10 cigarettes per day: aOR, 1.69; 95% CI, 1.28-2.23; non-Aboriginal, 1-10 cigarettes per day: aOR, 1.46; 95% CI, 1.34-1.58), preterm birth (Aboriginal, 1-10 cigarettes per day: aOR, 1.40; 95% CI, 1.14-1.73; non-Aboriginal, 1-10 cigarettes per day: aOR, 1.48; 95% CI, 1.39-1.57), intrauterine growth restriction (Aboriginal, 1-10 cigarettes per day: aOR, 2.33; 95% CI, 1.77-3.08; non-Aboriginal, 1-10 cigarettes per day: aOR, 2.65; 95% CI, 2.48-2.83) and small for gestational age (Aboriginal, 1-10 cigarettes per day: aOR, 2.49; 95% CI, 2.06-3.00; non-Aboriginal, 1-10 cigarettes per day: aOR, 2.29; 95% CI, 2.20-2.40). For both Aboriginal and non-Aboriginal women who smoked 11 or more cigarettes per day the aOR for these outcomes increased. Smoking cessation in the first trimester reduced these risks to levels comparable with non-smokers. The risk of each adverse outcome was greater in Aboriginal than non-Aboriginal women for all smoking categories; however, interactions between Aboriginal status and smoking were not significant, indicating an equal contribution of smoking to poor outcomes in both populations. Conclusions: Smoking cessation or reduction during pregnancy would significantly improve outcomes in both Aboriginal and non-Aboriginal women. This should be made a clear priority to improve pregnancy outcomes for all women.
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2014 |
Abumaree MH, Alahari S, Albrecht C, Aye ILMH, Bainbridge S, Chauvin S, et al., 'IFPA Meeting 2013 Workshop Report I: Diabetes in pregnancy, maternal dyslipidemia in pregnancy, oxygen in placental development, stem cells and pregnancy pathology', Placenta, 35 (2014) [C1]
Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2013 there were twelve themed workshops, four of whi... [more]
Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2013 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) diabetes in pregnancy; 2) lipids, fatty acids and the placenta; 3) oxygen in placental development and pathologies; 4) stem cells and pathologies. © 2013 Published by IFPA and Elsevier Ltd.
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2014 |
Saif Z, Hodyl NA, Hobbs E, Tuck AR, Butler MS, Osei-Kumah A, Clifton VL, 'The human placenta expresses multiple glucocorticoid receptor isoforms that are altered by fetal sex, growth restriction and maternal asthma', Placenta, 35 260-268 (2014) [C1]
Introduction We have previously identified sex-specific differences in the fetal-placental response to cortisol. Our recent studies suggest that this differential response to cort... [more]
Introduction We have previously identified sex-specific differences in the fetal-placental response to cortisol. Our recent studies suggest that this differential response to cortisol is driven by differences in glucocorticoid receptor (GR) protein function rather than through changes in gene transcription or protein expression. Methods This study was designed to define whether the human placenta expresses different isoforms of the GR and whether expression was altered by fetal sex and maternal asthma. Asthma and non-asthma pregnant women were prospectively recruited at their first antenatal visit and placentae collected at delivery. Placental GR expression was examined in relation to maternal asthma, fetal sex and birthweight. Results Twelve specific bands for the GR were identified at molecular weights of 94, 91, 81, 74, 69, 68, 65, 60, 55, 50, 48 and 38 kDa. The 12 isoforms were localised to the placental trophoblast and expression varied in relation to cellular location in either the cytoplasm or nucleus, fetal sex, fetal size and the presence and absence of maternal asthma. Conclusion This is the first study to identify the presence of several protein isoforms of the GR in the human placenta. The data suggest glucocorticoid resistance observed in male placentae may be mediated through increased GRß, GR A and GR P localisation to the nucleus. While female placentae may be more sensitive to cortisol in the presence of maternal asthma through a decrease in GRß and an enhancement GRa activity via an interaction with GRa D3 and GRa C. © 2014 Elsevier Ltd.
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2014 |
Sadovsky Y, Clifton VL, Burton GJ, 'Invigorating placental research through the "human Placenta Project"', Placenta, 35 527 (2014)
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2014 |
Burton GJ, Clifton V, Sadovsky Y, 'Congratulations!', Placenta, 35 973 (2014)
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2014 |
Wooldridge AL, Bischof RJ, Meeusen EN, Liu H, Heinemann GK, Hunter DS, et al., 'Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 306 (2014) [C1]
Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. W... [more]
Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming. © 2014 the American Physiological Society.
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2014 |
Hodyl NA, Stark MJ, Scheil W, Grzeskowiak LE, Clifton VL, 'Perinatal outcomes following maternal asthma and cigarette smoking during pregnancy', European Respiratory Journal, 43 704-716 (2014) [C1]
Does cigarette smoking in pregnancy explain the increased risk of adverse perinatal outcomes that occur with maternal asthma or does it compound the effect? Using population based... [more]
Does cigarette smoking in pregnancy explain the increased risk of adverse perinatal outcomes that occur with maternal asthma or does it compound the effect? Using population based birth records, a retrospective analysis was conducted of all singleton pregnancies in South Australia over 10 years (1999-2008; n5172 305), examining maternal asthma, cigarette smoking and quantity of smoking to estimate odds ratios. Compared with nonasthmatic females who did not smoke during pregnancy, both asthmatic females who smoked and those who did not smoke during pregnancy had a significantly increased risk of gestational diabetes, antepartum haemorrhage, polyhydramnios, premature rupture of membranes, emergency Caesarean section, and the child being small for gestational age and having congenital abnormalities. These associations suggest that asthma, independently of maternal smoking, increases the risk of these adverse perinatal outcomes. Maternal smoking was itself associated with an increased risk of a number of poor neonatal outcomes, with a dose-response relationship observed. Notably, maternal asthma combined with cigarette smoking significantly increased the risk of preterm birth and urinary tract infections to a greater degree than with either exposure alone. Maternal asthma and cigarette smoking during pregnancy are both independently associated with adverse perinatal outcomes and, combined, compound the risk of preterm birth and urinary tract infections.
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2014 |
Dalton JA, Rodger DL, Wilmore M, Skuse AJ, Humphreys S, Flabouris M, Clifton VL, '"Who's afraid?": Attitudes of midwives to the use of information and communication technologies (ICTs) for delivery of pregnancy-related health information', Women and Birth, 27 168-173 (2014)
Background: Usage rates for information and communication technologies (ICTs) in healthcare have been increasing in recent years, but often lag behind general usage rates for popu... [more]
Background: Usage rates for information and communication technologies (ICTs) in healthcare have been increasing in recent years, but often lag behind general usage rates for populations as a whole. Research into such differential rates of ICT use across different segments of the population has identified a number of possible causal factors that limit usage. Aim: The research investigated midwives' attitudes and experiences of ICT use to identify potential causal factors that encourage or inhibit their usage in antenatal care. Methods: Semi-structured interviews, focus groups and short surveys were conducted with midwives who provide antenatal education at an Australian metropolitan hospital. Thematic and statistical analyses were used to interpret the data. Findings: Although midwives recognised the potential benefits of using ICTs to deliver pregnancy-related health information many had reservations about their use in everyday work. These reservations centred on lack of training in use of ICTs, the perceived legal risks associated with social media, potential violations of patient privacy, misdiagnosis and misunderstandings between midwife and client. Conclusion: Midwives face a number of barriers to effective use of ICTs in healthcare including material access, skills access, usage access and motivational access. Motivational access appears to be a key concern due to the high perception of risk associated with social media in particular. Reducing the motivational barriers through a range of interventions with midwifery staff may assist in overcoming other barriers to ICT use in antenatal care. Further research is required to determine whether these findings are generalisable to other healthcare contexts. © 2014 Australian College of Midwives.
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2014 |
Grzeskowiak LE, Dekker G, Rivers K, Roberts-Thomson K, Roy A, Smith B, et al., 'A randomized controlled trial to assess the clinical and cost effectiveness of a nurse-led Antenatal Asthma Management Service in South Australia (AAMS study)', BMC Pregnancy and Childbirth, 14 (2014)
Background: Pregnancy presents a unique situation for the management of asthma as it can alter the course of asthma severity and its treatment, which in turn can affect pregnancy ... [more]
Background: Pregnancy presents a unique situation for the management of asthma as it can alter the course of asthma severity and its treatment, which in turn can affect pregnancy outcomes. Despite awareness of the substantial adverse effects associated with asthma during pregnancy, little has been done to improve its management and reduce associated perinatal morbidity and mortality. The aim of this randomized controlled trial is to evaluate the clinical and cost effectiveness of an Antenatal Asthma Management Service.Methods/design: Design: Multicentre, randomized controlled trial. Inclusion criteria: Women with physician diagnosed asthma, which is not currently in remission, who are less than 20 weeks gestation with a singleton pregnancy and do not have a chronic medical condition. Trial entry and randomization: Eligible women with asthma, stratified by treatment site, disease severity and parity, will be randomized into either the 'Standard Care Group' or the 'Intervention Group'. Study groups: Both groups will be followed prospectively throughout pregnancy. Women in the 'Standard Care Group' will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the 'Intervention Group' will receive additional care through the nurse-led Antenatal Asthma Management Service, based in the antenatal outpatient clinic. Women will receive asthma education with a full assessment of their asthma at 18, 24, 30 and 36 weeks gestation. Each antenatal visit will include a 60 min session where asthma management skills are assessed including: medication adherence and knowledge, inhaler device technique, recognition of asthma deterioration and possession of a written asthma action plan. Furthermore, subjects will receive education about asthma control and management skills including trigger avoidance and smoking cessation counseling when appropriate. Primary study outcome: Asthma exacerbations during pregnancy. Sample size: A sample size of 378 women will be sufficient to show an absolute reduction in asthma exacerbations during pregnancy of 20% (alpha 0.05 two-tailed, 90% power, 5% loss to follow-up).Discussion: The integration of an asthma education program within the antenatal clinic setting has the significant potential to improve the participation of pregnant women in the self-management of their asthma, reduce asthma exacerbations and improve perinatal health outcomes.Trial registration: ACTRN12613000244707. © 2014 Grzeskowiak et al.; licensee BioMed Central Ltd.
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2014 |
Bain E, Pierides KL, Clifton VL, Hodyl NA, Stark MJ, Crowther CA, Middleton P, 'Interventions for managing asthma in pregnancy', Cochrane Database of Systematic Reviews, 2014 (2014)
Background: Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evide... [more]
Background: Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evidence however, that the adequate control of asthma can improve health outcomes for mothers and their babies. Despite known risks of poorly controlled asthma during pregnancy, a large proportion of women have sub-optimal asthma control, due to concerns surrounding risks of pharmacological agents, and uncertainties regarding the effectiveness and safety of different management strategies. Objectives: To assess the effects of interventions (pharmacologic and non-pharmacologic) for managing women's asthma in pregnancy on maternal and fetal/infant outcomes. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 June 2014) and the Cochrane Airways Group's Trials Register (4 June 2014). Selection criteria: Randomised and quasi-randomised controlled trials comparing any intervention used to manage asthma in pregnancy, with placebo, no intervention, or an alternative intervention. We included pharmacological and non-pharmacological interventions (including combined interventions). Cluster-randomised trials were eligible for inclusion (but none were identified). Cross-over trials were not eligible for inclusion. We included multi-armed trials along with two-armed trials. We also included studies published as abstracts only. Data collection and analysis: At least two review authors independently assessed trial eligibility and quality and extracted data. Data were checked for accuracy. Main results: We included eight trials in this review, involving 1181 women and their babies. Overall we judged two trials to be at low risk of bias, two to be of unclear risk of bias, and four to be at moderate risk of bias. Five trials assessed pharmacological agents, including inhaled corticosteroids (beclomethasone or budesonide), inhaled magnesium sulphate, intravenous theophylline, and inhaled beclomethasone verus oral theophylline. Three trials assessed non-pharmacological interventions, including a fractional exhaled nitric oxide (FENO)-based algorithm versus a clinical guideline-based algorithm to adjust inhaled corticosteroid therapy, a pharmacist-led multi-disciplinary approach to management versus standard care, and progressive muscle relaxation (PMR) versus sham training. The eight included trials were assessed under seven separate comparisons. Pharmacological interventions Primary outcomes: one trial suggested that inhaled magnesium sulphate in addition to usual treatment could reduce exacerbation frequency in acute asthma (mean difference (MD) -2.80; 95% confidence interval (CI) -3.21 to -2.39; 60 women). One trial assessing the addition of intravenous theophylline to standard care in acute asthma did not report on exacerbations (65 women). No clear difference was shown in the risk of exacerbations with the use of inhaled beclomethasone in addition to usual treatment for maintenance therapy in one trial (risk ratio (RR) 0.36; 95% CI 0.13 to 1.05; 60 women); a second trial also showed no difference, however data were not clearly reported to allow inclusion in a meta-analysis. No difference was shown when inhaled beclomethasone was compared with oral theophylline for maintenance therapy (RR 0.88; 95% CI 0.59 to 1.33; one trial, 385 women). None of these trials reported on neonatal intensive care admissions. Secondary outcomes: inhaled magnesium sulphate in acute asthma was shown to improve lung function measures (one trial, 60 women); intravenous theophylline in acute asthma was not associated with benefits (one trial, 65 women). No clear differences were seen with the addition of inhaled corticosteroids to routine treatment in three trials (374 women). While inhaled beclomethasone, compared with oral theophylline, significantly reduced treatment discontinuation due to adverse effects in one trial (384 women), no ot...
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2013 |
Bain E, Pierides KL, Middleton P, Clifton VL, Hodyl NA, Stark MJ, Crowther CA, 'Interventions for managing asthma in pregnancy', Cochrane Database of Systematic Reviews, 2013 (2013)
This is the protocol for a review and there is no abstract. The objectives are as follows: The aim of this review is to systematically assess the effects of interventions (pharmac... [more]
This is the protocol for a review and there is no abstract. The objectives are as follows: The aim of this review is to systematically assess the effects of interventions (pharmacologic and non-pharmacologic, including self-management interventions) for managing women's asthma in pregnancy on maternal and fetal/infant outcomes.
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2013 |
Grieger JA, Wood LG, Clifton VL, 'Improving asthma during pregnancy with dietary antioxidants: The current evidence', Nutrients, 5 3212-3234 (2013) [C1]
The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induc... [more]
The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS). Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i) review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii) provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
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2013 |
Burton GJ, Sadovsky Y, Clifton V, 'Prizes galore!', Placenta, 34 1 (2013)
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2013 |
Powell H, McCaffery K, Murphy VE, Hensley MJ, Clifton VL, Giles W, Gibson PG, 'Psychosocial Variables Are Related to Future Exacerbation Risk and Perinatal Outcomes in Pregnant Women with Asthma', JOURNAL OF ASTHMA, 50 383-389 (2013) [C1]
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Nova |
2013 |
Zouikr I, Tadros MA, Clifton VL, Beagley KW, Hodgson DM, 'Low Formalin Concentrations Induce Fine-Tuned Responses That Are Sex and Age-Dependent: A Developmental Study', PLOS ONE, 8 (2013) [C1]
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Nova |
2013 |
Hodyl NA, Stark MJ, Butler M, Clifton VL, 'Placental P-glycoprotein is unaffected by timing of antenatal glucocorticoid therapy but reduced in SGA preterm infants', Placenta, 34 325-330 (2013) [C1]
Introduction: The beneficial effects of antenatal glucocorticoid therapy on fetal lung maturation require their passage across the placental glucocorticoid barrier, composed of gl... [more]
Introduction: The beneficial effects of antenatal glucocorticoid therapy on fetal lung maturation require their passage across the placental glucocorticoid barrier, composed of glucocorticoid metabolising enzymes, such as 11 beta hydroxysteroid dehydrogenase (11ßHSD), and proteins that efflux glucocorticoids, such as P-glycoprotein (P-gp). We have shown that 11ßHSD2 activity is responsive to antenatal glucocorticoids, however the effect on placental P-gp remains unknown. Since antenatal glucocorticoids have a greater prophylactic effect in females compared to males, we also assessed whether this therapy induced sexually dimorphic effects on P-gp expression, as well as on placental inflammatory processes mediated by corticosteroids. Methods: Placentas were collected from 53 women presenting in threatened preterm labour, and processed to assess cytokine and P-gp mRNA expression, as well as P-gp localisation using immunohistochemistry. Results: Placental cytokine, P-gp mRNA and protein expression were not altered by timing of antenatal glucocorticoids or fetal sex. However, both P-gp mRNA and protein expression were significantly reduced in placentas from infants born small for gestational age (SGA) compared to appropriately grown infants (p < 0.05), suggesting a role for P-gp in its pathogenesis via the provision of a net increase in fetal exposure to bioactive exogenous glucocorticoids. Conclusions: While this study identified no change in placental P-gp following antenatal glucocorticoids, it has provided evidence that P-gp plays an important role in cases of SGA. This supports the known mechanistic relationship between antenatal glucocorticoids, fetal development and the postnatal phenotype. Given that P-gp also confers fetal protection from a number of drugs, this finding warrants further investigation to improve clinical management of the SGA fetus. © 2013 Elsevier Ltd. All rights reserved.
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2013 |
Rodger D, Skuse A, Wilmore M, Humphreys S, Dalton J, Flabouris M, Clifton VL, 'Pregnant women's use of information and communications technologies to access pregnancy-related health information in South Australia', Australian Journal of Primary Health, 19 308-312 (2013)
This paper examines how pregnant women living in South Australia use information and communication technologies (ICTs), principally Internet and mobile phones, to access pregnancy... [more]
This paper examines how pregnant women living in South Australia use information and communication technologies (ICTs), principally Internet and mobile phones, to access pregnancy-related information. It draws on 35 semistructured interviews conducted as part of the 'Health-e Baby' project, a qualitative study designed to assess the information needs and ICT preferences of pregnant women cared for at a South Australian metropolitan teaching hospital. Our research shows that although ICTs offer exciting possibilities for health promotion and the potential for new forms of communication, networking and connection, we cannot assume the effectiveness of communicating through such channels, despite near universal levels of ICT access. In turn, this highlights that if e-mediated health promotion is to be effective, health promoters and practitioners need to better understand ICT access, usage and content preferences of their clients. © 2013 La Trobe University.
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2013 |
Stark MJ, Clifton VL, Hodyl NA, 'Differential effects of docosahexaenoic acid on preterm and term placental pro-oxidant/antioxidant balance', Reproduction, 146 243-251 (2013) [C1]
Docosahexaenoic acid (DHA) supplementation in pregnancy may confer some clinical benefits; however, this compound can exert pro-oxidant effects. In this study, we investigated the... [more]
Docosahexaenoic acid (DHA) supplementation in pregnancy may confer some clinical benefits; however, this compound can exert pro-oxidant effects. In this study, we investigated the effects of DHA on pro-oxidant/antioxidant balance in term and preterm placental explants, assessing oxidative stress marker concentrations, antioxidant capacity and pro-inflammatory cytokine production. Term (n=8) and preterm (n=9) placental explants were exposed to lipopolysaccharide (LPS, 1 ng/ml), DHA (1, 10 and 100 µM), and DHA and LPS simultaneously or pre-treated with DHA for 24 h prior to LPS treatment. The production of malondialdehyde (MDA, lipid peroxidation), 8-hydroxy-2-deoxy guanosine (8-OHdG, oxidative DNA damage) and pro-inflammatory cytokines (tumour necrosis factor a (TNFa), interleukin 6 and interferon-¿) and total antioxidant capacity were measured. DHA at a concentration of 100 µM induced oxidative stress in term placentas, while at all the three concentrations, it induced oxidative stress in preterm placentas. DHA and LPS resulted in reduced MDA levels in term (P<0.005) and preterm (P=0.004) placentas and reduced 8-OHdG levels in preterm placentas (P=0.035). DHA pre-treatment, but not co-treatment with LPS, reduced 8-OHdG levels (P<0.001) in term placentas. DHA increased antioxidant capacity only in term placentas (P<0.001), with lower antioxidant capacity being observed overall in preterm placentas compared with term placentas (P=0.001). In term placentas, but not in preterm ones, DHA co-treatment and pre-treatment reduced LPS-induced TNFa levels. The ability of DHA to alter placental pro-oxidant/antioxidant balance is dependent on the DHA concentration used and the gestational age of the placental tissue. DHA has a greater capacity to increase oxidative stress in preterm placentas, but it offers greater protection against inflammation-induced oxidative stress in term placentas. This appears to be a result of DHA altering placental antioxidant capacity. These data have implications for the timing and concentration of DHA supplementation in pregnancy. © 2013 Society for Reproduction and Fertility.
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2013 |
Tucker J, Wilson A, Clifton V, 'Women's experience of anal incontinence following a history of obstetric anal sphincter injury: A literature review', International Journal of Evidence-Based Healthcare, 11 181-186 (2013)
Background: Anal incontinence (AI) is the involuntary loss of a liquid or solid stool and flatus, resulting in a lifelong profound negative impact on a person's quality of li... [more]
Background: Anal incontinence (AI) is the involuntary loss of a liquid or solid stool and flatus, resulting in a lifelong profound negative impact on a person's quality of life. One million Australians, half of whom are women, are affected by AI. The aetiology of AI is reported within research literature. Importantly obstetric anal sphincter injury following vaginal delivery is a predominant cause of AI. Factors cited as major risk factors of anal sphincter damage include instrumental delivery, macrosomia and primiparity. The incidence of AI increases with age and with further vaginal delivery. The impact lasts for life. Aim: This study aims to identify women's experiences of AI following obstetric anal sphincter injury and their impact on quality of life. Method: An extensive online literature search was undertaken within the medical and nursing databases including the Cumulative Index of Nursing and Allied Health Literature, Scopus, PubMed and Medline. Key search terms included AI, faecal incontinence, anal sphincter injuries, obstetric complications, trauma, obstetric, postnatal care, experiences, women's experience and quality of life. The literature search was further refined through fields that included English language only, literature published between 2000 and 2012 and full-text articles. Findings: The review identified a significant amount of research literature that addressed the prevalence and cause of AI. While quality of life questionaries and symptom severity scores have been utilised to assess the impact of AI on a person's life, there are inherent weaknesses in providing the experience of AI on a person's life. Furthermore, there is limited in-depth research that addresses women's experiences of AI following a history of obstetric anal sphincter injury and the impact on their quality of life. Conclusion: Research findings contribute to understanding the prevalence, physical, social and emotional impact of AI. While alterations in clinical practice can improve the identification and management of AI, further research that builds on the state of knowledge and seeks a deeper understanding of the issues for women with AI as a result of obstetric anal sphincter injury is required. © 2013 The Authors International Journal of Evidence-Based Healthcare © 2013 The Joanna Briggs Institute.
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2013 |
Clifton VL, Hodyl NA, Fogarty PA, Torpy DJ, Roberts R, Nettelbeck T, et al., 'The impact of iodine supplementation and bread fortification on urinary iodine concentrations in a mildly iodine deficient population of pregnant women in South Australia', Nutrition Journal, 12 (2013)
Mild iodine deficiency during pregnancy can have significant effects on fetal development and future cognitive function. The purpose of this study was to characterise the iodine s... [more]
Mild iodine deficiency during pregnancy can have significant effects on fetal development and future cognitive function. The purpose of this study was to characterise the iodine status of South Australian women during pregnancy and relate it to the use of iodine-containing multivitamins. The impact of fortification of bread with iodized salt was also assessed. Women (n = 196) were recruited prospectively at the beginning of pregnancy and urine collected at 12, 18, 30, 36 weeks gestation and 6 months postpartum. The use of a multivitamin supplement was recorded at each visit. Spot urinary iodine concentrations (UIC) were assessed. Median UICs were within the mildly deficient range in women not taking supplements (<90 µg/L). Among the women taking iodine-containing multivitamins UICs were within WHO recommendations (150-249 µg/L) for sufficiency and showed an increasing trend through gestation. The fortification of bread with iodized salt increased the median UIC from 68 µg/L to 84 µg/L (p =.011) which was still in the deficient range. Pregnant women in this region of Australia were unlikely to reach recommended iodine levels without an iodine supplement, even after the mandatory iodine supplementation of bread was instituted in October 2009. © 2013 Clifton et al.; licensee BioMed Central Ltd.
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2012 |
Wynne OL, Horvat JC, Smith R, Hansbro PM, Clifton VL, Hodgson DM, 'Effect of neonatal respiratory infection on adult BALB/c hippocampal glucocorticoid and mineralocorticoid receptors', Developmental Psychobiology, 54 568-575 (2012) [C1]
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Nova |
2012 |
Tolosa Gonzalez JM, Schjenken JE, Clifton VL, Vargas A, Barbeau B, Lowry P, et al., 'The endogenous retroviral envelope protein syncytin-1 inhibits LPS/PHA-stimulated cytokine responses in human blood and is sorted into placental exosomes', Placenta, 33 933-941 (2012) [C1]
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Nova |
2012 |
Sadovsky Y, Clifton VL, Burton GJ, 'The impact of impact factors', Placenta, 33 753 (2012)
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2012 |
McLernon PC, Wood LG, Murphy VE, Hodyl NA, Clifton VL, 'Circulating antioxidant profile of pregnant women with asthma', Clinical Nutrition, 31 99-107 (2012) [C1]
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Nova |
2012 |
Burton GJ, Clifton V, Sadovsky Y, 'To Harold Fox Our thanks', Placenta, 33 459 (2012)
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2012 |
Stark MJ, Hodyl NA, Butler M, Clifton VL, 'Localisation and characterisation of uncoupling protein-2 (UCP2) in the human preterm placenta', PLACENTA, 33 1020-1025 (2012)
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2012 |
Clifton VL, Davies M, Moore V, Wright IM, Ali Z, Hodyl NA, 'Developmental perturbation induced by maternal asthma during pregnancy: The short- and long-term impacts on offspring', Journal of Pregnancy, 2012 1-8 (2012) [C1]
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Nova |
2012 |
McLernon PC, Wood LG, Murphy VE, Hodyl NA, Clifton VL, 'Fatty acid profile of pregnant women with asthma', e-SPEN Journal, 7 e78-e85 (2012) [C1]
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Nova |
2011 |
Stark MJ, Hodyl NA, Wright IM, Clifton V, 'The influence of sex and antenatal betamethasone exposure on vasoconstrictors and the preterm microvasculature', Journal of Maternal-Fetal & Neonatal Medicine, 24 1215-1220 (2011) [C1]
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Nova |
2011 |
Al-Khan A, Aye IL, Barsoum I, Borbelyd A, Cebral E, Cerchi G, et al., 'IFPA Meeting 2010 Workshops Report II: Placental pathology; Trophoblast invasion; Fetal sex; Parasites and the placenta; Decidua and embryonic or fetal loss; Trophoblast differentiation and syncytialisation', PLACENTA, 32 S90-S99 (2011)
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2011 |
Powell GH, Murphy VE, Taylor DR, Hensley MJ, McCaffery K, Giles W, et al., 'Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: A double-blind, randomised controlled trial', The Lancet, 378 983-990 (2011) [C1]
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Nova |
2011 |
Stark MJ, Hodyl NA, Wright IM, Clifton VL, 'Influence of sex and glucocorticoid exposure on preterm placental pro-oxidant-antioxidant balance', Placenta, 32 865-870 (2011) [C1]
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Nova |
2011 |
Scott NM, Hodyl NA, Osei-Kumah A, Stark MJ, Smith R, Clifton VL, 'The presence of maternal asthma during pregnancy suppresses the placental pro-inflammatory response to an immune challenge in vitro', Placenta, 32 454-461 (2011) [C1]
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Nova |
2011 |
Osei-Kumah A, Smith R, Jurisica I, Caniggia I, Clifton VL, 'Sex-specific differences in placental global gene expression in pregnancies complicated by asthma', Placenta, 32 570-578 (2011) [C1]
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Nova |
2011 |
Powell H, McCaffery K, Murphy VE, Hensley MJ, Clifton VL, Giles WB, Gibson PG, 'Psychosocial outcomes are related to asthma control and quality of life in pregnant women with asthma', Journal of Asthma, 48 1032-1040 (2011) [C1]
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Nova |
2011 |
Wynne OL, Horvat JC, Kim RY, Ong LK, Smith R, Hansbro PM, et al., 'Neonatal respiratory infection and adult re-infection: Effect on glucocorticoid and mineralocorticoid receptors in the hippocampus in BALB/c mice', Brain Behavior and Immunity, 25 1214-1222 (2011) [C1]
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Nova |
2011 |
Wynne OL, Horvat JC, Osei-Kumah A, Smith R, Hansbro PM, Clifton VL, Hodgson DM, 'Early life infection alters adult BALB/c hippocampal gene expression in a sex specific manner', Stress-the International Journal on the Biology of Stress, 14 247-261 (2011) [C1]
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Nova |
2011 |
Hodyl NA, Stark MJ, Osei-Kumah A, Clifton VL, 'Prenatal programming of the innate immune response following in utero exposure to inflammation: a sexually dimorphic process?', EXPERT REVIEW OF CLINICAL IMMUNOLOGY, 7 579-592 (2011)
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2011 |
Hodyl NA, Stark MJ, Osei-Kumah A, Bowman M, Gibson PG, Clifton VL, 'Fetal glucocorticoid-regulated pathways are not affected by inhaled corticosteroid use for asthma during pregnancy', American Journal of Respiratory and Critical Care Medicine, 183 716-722 (2011) [C1]
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Nova |
2011 |
Zarzycki PK, Zarzycka MB, Clifton VL, Adamski J, Glód BK, 'Low-parachor solvents extraction and thermostated micro-thin-layer chromatography separation for fast screening and classification of spirulina from pharmaceutical formulations and food samples', Journal of Chromatography A, 1218 5694-5704 (2011)
The goal of this paper is to demonstrate the separation and detection capability of eco-friendly micro-TLC technique for the classification of spirulina and selected herbs from ph... [more]
The goal of this paper is to demonstrate the separation and detection capability of eco-friendly micro-TLC technique for the classification of spirulina and selected herbs from pharmaceutical and food products. Target compounds were extracted using relatively low-parachor liquids. A number of the spirulina samples which originated from pharmaceutical formulations and food products, were isolated using a simple one step extraction with small volume of methanol, acetone or tetrahydrofuran. Herb samples rich in chlorophyll dyes were analyzed as reference materials. Quantitative data derived from micro-plates under visible light conditions and after iodine staining were explored using chemometrics tools including cluster analysis and principal components analysis. Using this method we could easily distinguish genuine spirulina and non-spirulina samples as well as fresh from expired commercial products and furthermore, we could identify some biodegradation peaks appearing on micro-TLC profiles. This methodology can be applied as a fast screening or fingerprinting tool for the classification of genuine spirulina and herb samples and in particular may be used commercially for the rapid quality control screening of products. Furthermore, this approach allows low-cost fractionation of target substances including cyanobacteria pigments in raw biological or environmental samples for preliminary chemotaxonomic investigations. Due to the low consumption of the mobile phase (usually less than 1. mL per run), this method can be considered as environmentally friendly analytical tool, which may be an alternative for fingerprinting protocols based on HPLC machines and simple separation systems involving planar micro-fluidic or micro-chip devices. © 2011 Elsevier B.V.
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2011 |
Prescott SL, Tulic M, Osei-Kumah A, Richman T, Crook M, Martino D, et al., 'Reduced placental FOXP3 associated with subsequent infant allergic disease', Journal of Allergy and Clinical Immunology, 128 (2011)
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2010 |
Hodyl NA, Walker FR, Krivanek K, Clifton VL, Hodgson DM, 'Prenatal endotoxin exposure alters behavioural pain responses to lipopolysaccharide in adult offspring', Physiology & Behavior, 100 143-147 (2010) [C1]
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Nova |
2010 |
Murphy VE, Clifton VL, Gibson PG, 'The effect of cigarette smoking on asthma control during exacerbations in pregnant women', Thorax, 65 739-744 (2010) [C1]
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Nova |
2010 |
Hodyl NA, Wyper HJ, Osei-Kumah A, Scott NM, Murphy VE, Gibson PG, et al., 'Sex-specific associations between cortisol and birth weight in pregnancies complicated by asthma are not due to differential glucocorticoid receptor expression', Thorax, 65 677-683 (2010) [C1]
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Nova |
2010 |
Osei-Kumah A, Wark PA, Smith R, Clifton VL, 'Asthma during pregnancy alters immune cell profile and airway epithelial chemokine release', Inflammation Research, 59 349-358 (2010) [C1]
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Nova |
2010 |
Clifton VL, Hodyl NA, Murphy VE, Giles WB, Baxter RC, Smith R, 'Effect of maternal asthma, inhaled glucocorticoids and cigarette use during pregnancy on the newborn insulin-like growth factor axis', Growth Hormone and IGF Research, 20 39-48 (2010) [C1]
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Nova |
2010 |
Lash GE, Burton GJ, Chamley LW, Clifton VL, Constancia M, Crocker IP, et al., 'IFPA Meeting 2009 Workshops Report', PLACENTA, 31 S4-S20 (2010)
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2010 |
Clifton VL, 'Review: Sex and the Human Placenta: Mediating Differential Strategies of Fetal Growth and Survival', Placenta, 31 (2010)
There are known sex specific differences in fetal and neonatal morbidity and mortality. There are also known differences in birthweight centile with males generally being larger t... [more]
There are known sex specific differences in fetal and neonatal morbidity and mortality. There are also known differences in birthweight centile with males generally being larger than females at birth. These differences are generally ignored when studying obstetric complications of pregnancy and the mechanisms that confer these differences between the sexes are unknown. Current evidence suggests sex specific adaptation of the placenta may be central to the differences in fetal growth and survival. Our research examining pregnancies complicated by asthma has reported sexually dimorphic differences in fetal growth and survival with males adapting placental function to allow for continued growth in an adverse maternal environment while females reduce growth in an attempt to survive further maternal insults. We have reported sex differences in placental cytokine expression, insulin-like growth factor pathways and the placental response to cortisol in relation to the complication of asthma during pregnancy. More recently we have identified sex specific alterations in placental function in pregnancies complicated by preterm delivery which were associated with neonatal outcome and survival. We propose the sexually dimorphic differences in growth and survival of the fetus are mediated by the sex specific function of the human placenta. This review will present evidence supporting this hypothesis and will argue that to ignore the sex of the placenta is no longer sound scientific practice. Crown Copyright © 2010.
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2010 |
Zarzycki PK, Zarzycka MB, Slaczka MM, Clifton VL, 'Acetonitrile, the polarity chameleon', Analytical and Bioanalytical Chemistry, 397 905-908 (2010)
Acetonitrile (CH 3 CN, ACN) is a relatively nontoxic, highly volatile and aprotic polar organic solvent. ACN plays a key role as an extraction and deproteinization medium for a va... [more]
Acetonitrile (CH 3 CN, ACN) is a relatively nontoxic, highly volatile and aprotic polar organic solvent. ACN plays a key role as an extraction and deproteinization medium for a variety of pre-purification and concentration techniques using liquid-liquid extraction, solid-phase extraction (SPE) or microextraction (SPME) protocols. In terms of polarity, acetonitrile shows a number of unexpected physicochemical properties that may strongly affect the final results of analytical protocols applied in detection and separation science. Strong hydrogen bonding and the creation of low-polar self-associated forms of acetonitrile affect a number of physical and chemical properties of acetonitrile-water mixtures. The relatively low polarity of pure ACN can easily be disrupted by the presence of a small amount of water, which is usually present in either the raw biological sample or the ACN itself. The phenomenon of acetonitrile-water phase splitting at subambient temperature provides a convenient way to deproteinize biological samples and to preconcentrate target analytes.
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2009 |
Clifton VL, Engel PJ, Smith R, Gibson PG, Brinsmead MW, Giles WB, 'Maternal and neonatal outcomes of pregnancies complicated by asthma in an Australian population', Australian and New Zealand Journal of Obstetrics and Gynaecology, 49 619-626 (2009) [C1]
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Nova |
2009 |
Scott NM, Hodyl NA, Murphy VE, Osei-Kumah A, Wyper H, Hodgson DM, et al., 'Placental cytokine expression covaries with maternal asthma severity and fetal sex', Journal of Immunology, 182 1411-1420 (2009) [C1]
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Nova |
2009 |
Stark MJ, Clifton VL, Wright IM, 'Neonates born to mothers with preeclampsia exhibit sex-specific alterations in microvascular function', Pediatric Research, 65 291-295 (2009) [C1]
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Nova |
2009 |
Stark MJ, Clifton VL, Wright IM, 'Carbon monoxide is a significant mediator of cardiovascular status following preterm birth', Pediatrics, 124 277-284 (2009) [C1]
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Nova |
2009 |
Stark MJ, Wright IM, Clifton VL, 'Sex-specific alterations in placental 11 beta-hydroxysteroid dehydrogenase 2 activity and early postnatal clinical course following antenatal betamethasone', American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 297 R510-R514 (2009) [C1]
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Nova |
2009 |
Vu TT, Hirst JJ, Stark MJ, Wright IM, Palliser HK, Hodyl NA, Clifton VL, 'Changes in human placental 5 alpha-reductase isoenzyme expression with advancing gestation: Effects of fetal sex and glucocorticoid exposure', Reproduction Fertility and Development, 21 599-607 (2009) [C1]
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Nova |
2009 |
Prescott SL, Clifton V, 'Asthma and pregnancy: Emerging evidence of epigenetic interactions in utero', Current Opinion in Allergy and Clinical Immunology, 9 417-426 (2009)
PURPOSE OF REVIEW: Pregnancy is arguably the most critical period of developmental programming. Here, we particularly focus on the emerging paradigm that disease propensity is epi... [more]
PURPOSE OF REVIEW: Pregnancy is arguably the most critical period of developmental programming. Here, we particularly focus on the emerging paradigm that disease propensity is epigenetically determined by maternal exposures that have the capacity to activate or silence fetal genes through alterations in DNA and histone methylation, histone acetylation, and chromatin structure. RECENT FINDINGS: The most notable recent candidate to emerge in this role has been dietary folate, a methyl donor clearly associated with changes in gene expression and disease susceptibility through gene hypermethylation. Animal studies also provide the first evidence that the allergy protective effects of microbial exposure in pregnancy may be mediated by changes in methylation of Th1 genes of the offspring. There is also emerging evidence that perinatal differences in immune function of allergy-prone newborns extend beyond previously recognized differences in effector T cell (Th1/Th2) function, to also include differences in neonatal regulatory T cell (Treg) and Th17 function, and moreover, that these pathways are also epigenetically regulated. SUMMARY: New studies reinforce the importance of in-utero exposures (including dietary nutrients, microbial products, cigarette smoking, and certain maternal mediations) in fetal immune development and in programming the susceptibility to asthma and allergic disease. © 2009 Lippincott Williams & Wilkins, Inc.
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2008 |
Osei-Kumah A, Smith R, Clifton VL, 'Maternal and cord plasma cytokine and chemokine profile in pregnancies complicated by asthma', Cytokine, 43 187-193 (2008) [C1]
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Nova |
2008 |
Stark MJ, Clifton VL, Wright IM, 'Microvascular flow, clinical illness severity and cardiovascular function in the preterm infant', Archives of Disease in Childhood Fetal & Neonatal Edition, 93 F271-F274 (2008) [C1]
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Nova |
2008 |
Engel PJ, Smith R, Brinsmead MW, Bowe SJ, Clifton VL, 'Male sex and pre-existing diabetes are independent risk factors for stillbirth', Australian & New Zealand Journal of Obstetrics & Gynaecology, 48 375-383 (2008) [C1]
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Nova |
2008 |
Johnson RF, Rennie N, Murphy VE, Zakar T, Clifton VL, Smith R, 'Expression of glucocorticoid receptor messenger ribonucleic acid transcripts in the human placenta at term', Journal of Clinical Endocrinology & Metabolism, 93 4887-4893 (2008) [C1]
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Nova |
2008 |
Stark MJ, Clifton VL, Wright IM, 'Sex-specific differences in peripheral microvascular blood flow in preterm infants', Pediatric Research, 63 415-419 (2008) [C1]
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Nova |
2008 |
Osei-Kumah A, Hodyl N, Clifton VL, 'Proteomics in asthma', Expert Review of Clinical Immunology, 4 713-721 (2008)
Proteomic approaches have already been successfully implemented in areas such as cancer research. Surprisingly, only a few proteomics analyses have been published reporting on the... [more]
Proteomic approaches have already been successfully implemented in areas such as cancer research. Surprisingly, only a few proteomics analyses have been published reporting on the protein profiles associated with asthma. Although proteomics has its limitations and experimental challenges, it can successfully contribute to the understanding of a complex disease such as asthma. We have reviewed the current literature that has reported the use of proteomic techniques to identify proteins that may contribute to altered lung function in asthma. Only a few of these studies have used proteomic techniques on human tissues associated with asthma, while most research has been performed with animal models of asthma. Proteomic applications have been used as a complimentary technique to verify the suspected candidate proteins involved in asthma. In addition, novel proteins have been identified as potential therapeutic targets. Future collaboration between the different scientific disciplines using proteomic studies of animal models of asthma and confirmation of these findings in human tissues will significantly contribute to the understanding of the etiology of asthma and lead to the development of new therapeutic strategies for this highly prevalent disease. © 2008 Expert Reviews Ltd.
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2008 |
Mayhew TM, Jenkins H, Todd B, Clifton VL, 'Maternal asthma and placental morphometry: Effects of severity, treatment and fetal sex', Placenta, 29 366-373 (2008) [C1]
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Nova |
2008 |
Hodyl NA, Krivanek K, Clifton VL, Hodgson DM, 'Innate immune dysfunction in the neonatal rat following prenatal endotoxin exposure', Journal of Neuroimmunology, 204 126-130 (2008) [C1]
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Nova |
2007 |
Tolosa Gonzalez JM, Schjenken JE, Civiti TD, Clifton VL, Smith R, 'Column-based method to simultaneously extract DNA, RNA, and proteins from the same sample', Biotechniques, 43 799-804 (2007) [C1]
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2007 |
Clifton VL, Bisits AM, Zarzycki PK, 'Characterization of human fetal cord blood steroid profiles in relation to fetal sex and mode of delivery using temperature-dependent inclusion chromatography and principal component analysis (PCA)', Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 855 249-254 (2007) [C1]
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Nova |
2007 |
Murphy VE, Fittock RJ, Zarzycki PK, Delahunty MM, Smith R, Clifton VL, 'Metabolism of synthetic steroids by the human placenta', Placenta, 28 39-46 (2007) [C1]
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2007 |
Hodyl NA, Krivanek K, Lawrence E, Clifton VL, Hodgson DM, 'Prenatal exposure to a pro-inflammatory stimulus causes delays in the development of the innate immune response to LPS in the offspring', Journal of Neuroimmunology, 190 61-71 (2007) [C1]
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2007 |
Hodyl NA, Walker FR, Krivanek K, Clifton VL, Hodgson DM, 'Modelling prenatal bacterial infection: Functional consequences of altered hypothalamic pituitary adrenal axis development', Behavioral Brain Research, 178 108-114 (2007) [C1]
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2006 |
Murphy VE, Clifton VL, Gibson PG, 'Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes', Thorax, 61 169-176 (2006) [C1]
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Nova |
2006 |
Osei-Kumah A, Ammit AJ, Smith R, Ge Q, Clifton VL, 'Inflammatory mediator release in normal bronchial smooth muscle cells is altered by pregnant maternal and fetal plasma independent of asthma', Placenta, 27 847-852 (2006) [C1]
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2006 |
Murphy VE, Smith R, Giles WB, Clifton VL, 'Endocrine regulation of human fetal growth: The role of the mother, placenta, and fetus', Endocrine Reviews, 27 141-169 (2006) [C1]
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Nova |
2006 |
Murphy VE, Johnson RF, Wang YC, Akinsanya K, Gibson PG, Smith R, Clifton VL, 'Proteomic study of plasma proteins in pregnant women with asthma', Respirology, 11 41-48 (2006) [C1]
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2006 |
Clifton VL, 'Maternal asthma during pregnancy and fetal outcomes: Potential mechanisms and possible solutions', Current Opinion in Allergy and Clinical Immunology, 6 307-311 (2006) [C2]
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2006 |
Zarzycki PK, Kulhanek KM, Smith R, Clifton VL, 'Determination of steroids in human plasma using temperature-dependent inclusion chromatography for metabolomic investigations', Journal of Chromatography A, 1104 203-208 (2006) [C1]
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2006 |
Stark MJ, Dierkx LM, Clifton VL, Wright IM, 'Alterations in the Maternal Peripheral Microvascular Response in Pregnancies Complicated by Preeclampsia and the Impact of Fetal Sex', Journal of the Society for Gynecologic Investigation, 13 573-578 (2006) [C1]
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Nova |
2006 |
Clifton VL, Rennie N, Murphy VE, 'Effect of inhaled glucocorticoid treatment on placental 11 beta-hydroxysteroid dehydrogenase type 2 activity and neonatal birthweight in pregnancies complicated by asthma', Australian and New Zealand Journal of Obstetrics and Gynaecology, 46 136-140 (2006) [C1]
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2005 |
Clifton VL, Vanderlelie J, Perkins AV, 'Increased anti-oxidant enzyme activity and biological oxidation in placentae of pregnancies complicated by maternal asthma', Placenta, 26 773-779 (2005) [C1]
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Nova |
2005 |
Vanderlelie J, Venardos K, Clifton VL, Gude NM, Clarke FM, Perkins AV, 'Increased Biological Oxidation and Reduced Anti-Oxidant Enzyme Activity in Pre-Eclamptic Placentae', Placenta, 26 53-58 (2005) [C1]
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2005 |
Clifton VL, 'Sexually Dimorphic Effects of Maternal Asthma During Pregnancy on Placental Glucocorticoid Metabolism and Fetal Growth', Cell and Tissue Research, 322 63-71 (2005) [C1]
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2005 |
Murphy VE, Gibson PG, Smith R, Clifton VL, 'Asthma during pregnancy: mechanisms and treatment implications', European Respiratory Journal, 25 731-750 (2005) [C1]
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2005 |
Murphy VE, Gibson PG, Talbot PI, Kessell CG, Clifton VL, 'Asthma self-management skills and the use of asthma education during pregnancy', European Respiratory Journal, 26 435-441 (2005) [C1]
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2005 |
Clifton VL, Crompton R, Read MA, Gibson PG, Smith R, Wright IM, 'Microvascular Effects of Corticotropin-Releasing Hormone in Human Skin Vary in Relation to Estrogen Concentration During the Menstrual Cycle', Journal of Endocrinology, 186 69-76 (2005) [C1]
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2005 |
Murphy VE, Johnson RF, Wang Y-C, Akinsanya K, Gibson PG, Smith R, Clifton VL, 'The Effect of Maternal Asthma on Placental and Cord Blood Protein Profiles', Society for Gynecological Investigation Journal, 12 349-355 (2005) [C1]
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2005 |
Murphy VE, Gibson PG, Talbot PI, Clifton VL, 'Severe asthma exacerbations during pregnancy', Obstetrics and Gynecology, 106 1046-1054 (2005) [C1]
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Nova |
2004 |
Johnson RF, Mitchell CM, Clifton VL, Zakar T, 'Regulation of 15-Hydroxyprostaglandin Dehydrogenase (PGDH) Gene Activity, Messenger Ribonucleic Acid Processing, and Protein Abundance in the Human Chorion in Late Gestation and Labour', The Journal of Clinical Endocrinology and Metabolism, 89 5639-5648 (2004) [C1]
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Nova |
2004 |
Clifton VL, Murphy VE, 'Maternal Asthma as a Model for Examining Fetal Sex-specific Effects on Maternal Physiology and Placental Mechanisms that Regulate Human Fetal Growth', Placenta, 18 S45-S52 (2004) [C1]
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2003 |
Crompton R, Clifton VL, Bisits AM, Read MA, Smith R, Wright IM, 'Corticotropin-releasing hormone causes vasodilation in human skin via mast cell-dependent pathways', Journal Of Clinical Endocrinology And Metabolism, 88 5427-5432 (2003) [C1]
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2003 |
Murphy VE, Clifton VL, 'Alterations in human placental 11 beta-hydroxysteroid dehydrogenase type 1 and 2 with gestational age and labour', Placenta, 24 739-744 (2003) [C1]
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2003 |
Murphy VE, Gibson PG, Giles WB, Zakar T, Smith R, Bisits AM, et al., 'Maternal Asthma Is Associated with Reduced Female Fetal Growth', American Journal of Respiratory & Critical Care Medicine, 168 1317-1323 (2003) [C1]
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Nova |
2003 |
Smith R, Mesiano S, Clifton V, Chan EC, Zakar T, Nicholson R, et al., 'The pathway to human birth', Cuadernos de Medicina Reproductiva, 9 43-51 (2003)
Preterm labour remains a major obstetric problem with only poor methods for prediction of preterm birth and treatments of preterm labour with limited efficacy. Regulation of human... [more]
Preterm labour remains a major obstetric problem with only poor methods for prediction of preterm birth and treatments of preterm labour with limited efficacy. Regulation of human parturition is demonstrably different from that in most animals restricting opportunities for relevant research. Recent work suggests a placental clock mechanism regulating the length of pregnancy through the production of the placental peptide Corticotrophin Releasing Hormone. At the end of pregnancy most animals initiate labour with a fall in circulating progesterone concentrations but this does not happen in humans. In humans a functional progesterone withdrawal is initiated by a change in myometrial expression of progesterone receptors, specifically increase expression of the PRA isoforms, which is a dominant repressor of the activating receptor PRB. This new knowledge may help design better strategies for prediction and treatment of preterm labour.
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2003 |
Smith R, Mesiano S, Clifton VL, Chan EC, Zakar T, Nicholson RC, et al., 'The Pathway to Human Birth', Cuadernos de Medicina Reproductiva, 9 43-51 (2003) [C1]
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2002 |
Clifton VL, Crompton R, Smith R, Wright ML, 'Microvascular Effects of CRH in Human Skin Vary in Relation to Gender', The Journal of Clinical Endocrinology & Metabolism, 87(1) 267-270 (2002) [C1]
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Nova |
2002 |
Murphy VE, Zakar T, Smith R, Giles WB, Gibson PG, Clifton VL, 'Reduced 11 -Hydroxysteroid Dehydrogenase Type 2 Activity Is Associated with Decreased Birth Weight Centile in Pregnancies Complicated by Asthma', The Journal of Clinical Endocrinology & Metabolism, 87(4) 1660-1668 (2002) [C1]
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2002 |
Clifton VL, Wallace EM, Smith R, 'Short-term effects of glucocorticoids in the human fetal-placental circulation in vitro', Journal of Clinical Endocrinology and Metabolism, 87 2838-2842 (2002) [C1]
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2002 |
Holloway AC, Howe DC, Chan G, Clifton VL, Smith R, Challis JRG, 'Urocortin: A mechanism for the sustained activation of the HPA axis in the late-gestation ovine fetus?', American Journal of Physiology - Endocrinology and Metabolism, 283 (2002)
We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in ... [more]
We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feed-forward of fetal hypothalamic-pituitary-adrenal function, leading to birth.
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2002 |
O'Dwyer DT, Clifton VL, Hall AL, Smith R, Robinson P, Crock PA, 'Pituitary Autoantibodies in Lymphocytic Hypophysitis Target Both - and - Enolase - A Link with Pregnancy?', Archives of Physiology and Biochemistry, 110(1-2) 94-98 (2002) [C1]
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2002 |
Schwartz J, Revskoy S, Redei E, Clifton VL, Smith R, Cherny R, 'Corticotrophs and peptides', Archives of Physiology and Biochemistry, 110 146-153 (2002) [C1]
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2002 |
Holloway AC, Howe DC, Chan G, Clifton VL, Smith R, Challis RG, 'Urocortin: A mechanism for the sustained activation of the HPA axis in the late gestation ovine fetus?', American Journal of Physiology Endocrinology and Metabolism, 283 165-171 (2002) [C1]
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2001 |
Clifton VL, Gu Q, Murphy VE, Schwartz J, Madsen G, Smith R, 'Erratum: Localization and characterization of urocortin during human pregnancy (Placenta (2000) vol. 21 (782-788))', Placenta, 22 264 (2001)
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2001 |
Gu Q, Clifton VL, Schwartz J, Madsen G, Sha JY, Smith R, 'Characterization of urocortin in human pregnancy', CHINESE MEDICAL JOURNAL, 114 618-622 (2001)
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2001 |
Clifton VL, Giles WB, Smith R, Bisits AM, Hempenstall P, Kessell C, Gibson PG, 'Alterations of Placental Vascular Function in Asthmatic Pregnancies', American Journal of Respiratory and Critical Care Medicine, 164 546-553 (2001) [C1]
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2000 |
McLean M, Bowman M, Clifton VL, Smith R, Grossman AB, 'Expression of the Heme Oxygenase-Carbon Monoxide Signalling system in Human Placenta', The Journal of Clinical Endocrinology & Metabolism, 85 2345-2349 (2000) [C1]
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2000 |
Clifton VL, Qing G, Murphy VE, Schwartz J, Madsen GM, Smith R, 'Localization and Characterization of Urocortin during Human Pregancy', Placenta, 21 782-788 (2000) [C1]
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1999 |
Patel FA, Clifton VL, Chwalisz K, Challis JRG, 'Steroid regulation of prostaglandin dehydrogenase activity and expression in human term placenta and chorio-decidua in relation to labor', Journal of Clinical Endocrinology and Metabolism, 84 291-299 (1999)
NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key catabolic enzyme controlling levels of biologically active PGs. PGDH is localized to syncytiotrophoblast in ... [more]
NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key catabolic enzyme controlling levels of biologically active PGs. PGDH is localized to syncytiotrophoblast in placenta, and to trophoblast cells in chorion. To examine the regulation of PGDH by steroids and to determine any changes with labor, we obtained placenta and chorion from term elective cesarean section or spontaneous delivery and isolated trophoblast cells using a Percoll density gradient. Cells were treated with varying concentrations of cortisol, progesterone, the synthetic progestins R5020, and medroxyprogesterone acetate with or without RU486 or the specific progesterone receptor antagonist, onapristone, and the 3ß-hydroxysteroid dehydrogenase inhibitor, trilostane. The activity of PGDH was assessed by measurement of 13,14-dihydro-15-keto-PGF(2a). PGDH messenger ribonucleic acid was quantified by in situ hybridization and computerized image analysis. The basal output of 13,14-dihydro-15-keto-PGF(2a) was lower in placenta or chorion collected at spontaneous labor than in that obtained at elective cesarean section. Cortisol had a significant dose-dependent inhibitory effect on PGDH activity in both placental and chorion trophoblast cells and significantly decreased levels of PGDH messenger ribonucleic acid. Responses were similar between tissues from laboring and nonlaboring women. PGDH activity was increased by R5020 and medroxyprogesterone acetate and was inhibited by RU486, onapristone, and trilostane. We conclude that cortisol inhibits PGDH activity and expression and that progestagens increase PGDH activity in human chorion and placenta.
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1998 |
Clifton VL, Telfer JF, Thompson AJ, Cameron IT, Teoh TG, Lye SJ, Challis JRG, 'Corticotropin-releasing hormone and proopiomelanocortin-derived peptides are present in human myometrium', Journal of Clinical Endocrinology and Metabolism, 83 3716-3721 (1998)
CRH and POMC-derived peptides are produced at a number of intrauterine sites in both the nonpregnant and pregnant states. It is hypothesized that CRH and POMC-derived peptides may... [more]
CRH and POMC-derived peptides are produced at a number of intrauterine sites in both the nonpregnant and pregnant states. It is hypothesized that CRH and POMC-derived peptides may be produced locally by the uterus to modulate myometrial contractility. This study has examined the distribution of these peptides in human uterine tissue during the ovulatory cycle and pregnancy. The immunoperoxidase staining method was used to localize CRH and POMC-derived peptides: ACTH, ß-endorphin, and aMSH. Immunoreactive (IR-) CRH and IR-POMC-derived peptides, ß-endorphin and aMSH, were observed in the myometrial smooth muscle, vascular smooth muscle, endometrial glandular epithelium, and luminal epithelium of the nonpregnant uterus (n = 17). Staining for IR-CRH did not change during the cycle from the proliferative (n = 8) to the secretory phases (n = 9). Conversely, staining for IR-ß- endorphin and IR-aMSH was only observed during the secretory phase of the cycle (n = 9). In uterine tissue obtained from pregnant women (n = 20) IR- CRH was present in the myometrial smooth muscle, vascular smooth muscle, decidua, and glandular epithelium. IR-POMC-derived peptides were not detectable at any uterine site during pregnancy (n = 20). IR-CRH was measurable in myometrial extracts collected from pregnant women undergoing cesarean section (20.9 ± 3.8 ng/g wet wt; n = 7) and from nonpregnant premenopausal women undergoing hysterectomy (7.7 ± 2.1 ng/g wet wt; n = 6). IR-CRH concentrations significantly increased with pregnancy. Levels of messenger ribonucleic acid encoding for CRH were examined in nonpregnant (n = 4) and pregnant (n = 10) myometrial smooth muscle and were also significantly increased with pregnancy. This study has demonstrated that levels of CRH and POMC peptide in human uterine tissue change with pregnancy and that CRH is produced locally by myometrial smooth muscle cells. These studies are consistent with the possibility that the CRH peptide has an autocrine/paracrine activity during pregnancy and labor that may be related to the modulation of myometrial contractility.
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1997 |
Clifton VL, Challis JRG, 'Placental corticotropin releasing hormone function during human pregnancy', Endocrinologist, 7 448-458 (1997)
Corticotropin releasing hormone (CRH) is produced in intrauterine sites including the placenta, decidua, and myometrium during human pregnancy. Placental CRH may have endocrine, p... [more]
Corticotropin releasing hormone (CRH) is produced in intrauterine sites including the placenta, decidua, and myometrium during human pregnancy. Placental CRH may have endocrine, paracrine, and autocrine functions. Its output into the maternal circulation increases as a function of gestation and correlates with increases in levels of mRNA encoding CRH in placental syncytiotrophoblast. Regulation of placental CRH expression and activity is multifactorial, being inhibited by progesterone and nitric oxide (NO), and stimulated by cytokines, neuropeptides, and glucocorticoids. CRH acts as a vasodilator in perfused placental tissue in vitro, may modulate maternal and fetal pituitary function, and has been implicated in mechanisms associated with the onset of labor at term and preterm.
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1996 |
Clifton VL, Read MA, Boura ALA, Robinson PJ, Smith R, 'Adrenocorticotropin causes vasodilatation in the human fetal-placental circulation', JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 81 1406-1410 (1996)
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1995 |
CLIFTON VL, OWENS PC, ROBINSON PJ, SMITH R, 'IDENTIFICATION AND CHARACTERIZATION OF A CORTICOTROPIN-RELEASING HORMONE-RECEPTOR IN HUMAN PLACENTA', EUROPEAN JOURNAL OF ENDOCRINOLOGY, 133 591-597 (1995)
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1995 |
CLIFTON VL, READ MA, LEITCH IM, GILES WB, BOURA ALA, ROBINSON PJ, SMITH R, 'CORTICOTROPIN-RELEASING HORMONE-INDUCED VASODILATATION IN THE HUMAN FETAL-PLACENTAL CIRCULATION - INVOLVEMENT OF THE NITRIC OXIDE CYCLIC GUANOSINE 3',5'-MONOPHOSPHATE-MEDIATED PATHWAY', JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 80 2888-2893 (1995)
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1994 |
CLIFTON VL, READ MA, LEITCH IM, BOURA ALA, ROBINSON PJ, SMITH R, 'CORTICOTROPIN-RELEASING HORMONE-INDUCED VASODILATATION IN THE HUMAN FETAL-PLACENTAL CIRCULATION', JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 79 666-669 (1994)
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1993 |
Kay DJ, Clifton V, Taylor JS, Boettcher B, 'Anti-sperm antibodies and semen profiles in re-anastomosed men', Reproduction, Fertility and Development, 5 135-139 (1993)
A group of 29 re-anastomosed men were examined with respect to semen quality, anti-sperm antibody titres in serum and seminal plasma, presence of anti-sperm antibodies on sperm, a... [more]
A group of 29 re-anastomosed men were examined with respect to semen quality, anti-sperm antibody titres in serum and seminal plasma, presence of anti-sperm antibodies on sperm, and success rate in inducing pregnancy. Results indicated no association between pre-reversal serum anti-sperm antibody titres and post-reversal semen quality, but a pregnancy induction rate of zero was associated with serum anti-sperm antibody titres greater than 160. It is recommended that men considering reversal, with anti-sperm antibody titres of this level, should receive counselling about the possibility of postreversal infertility. © 1993 CSIRO. All rights reserved.
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1992 |
CLIFTON VL, HUSBAND AJ, KAY DJ, 'LOCAL IMMUNITY IN THE MALE REPRODUCTIVE-TRACT', IMMUNOLOGY AND CELL BIOLOGY, 70 301-307 (1992)
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1992 |
CLIFTON VL, HUSBAND AJ, KAY DJ, 'Local immunity in the male reproductive tract', Immunology and Cell Biology, 70 301-307 (1992)
In previous studies we have demonstrated that the male urinary tract forms part of the common mucosal immune system, and that the gut contributes to local defences at this site.1 ... [more]
In previous studies we have demonstrated that the male urinary tract forms part of the common mucosal immune system, and that the gut contributes to local defences at this site.1 The question arises as to the extent to which the reproductive tract also forms part of the common mucosal immune system. Rats were immunized by a variety of routes designed to stimulate a local response in the intestine and/or the reproductive tract. Rats immunized only by the intratesticular (i.t.) route yielded no antibody-containing (ACC) response in any of the tissues examined. Intestinal immunization using intraperitoneal priming followed by intraduodenal challenge (i.p./i.d.) yielded a substantial IgA-specific ACC response in the jejunum, but no ACC were detectable in any of the reproductive tract tissues. However, when intestinal and testicular immunizations were combined, large numbers of IgA-specific antibodies were detected in all tissues examined. Chronic drainage of the thoracic lymphatic duct throughout the post-challenge period abrogated the ACC response in all tissues of the reproductive tract, indicating that the ACC appearing at these sites after immunization were of gut origin. The IgA-specific anti-OVA antibody detectable in serum, saliva and testis homogenate reflected the ACC counts in histological sections. The studies reported here confirm that the male reproductive tract does form part of a common mucosal immune system and that gut-associated lymphoid tissues may contribute cellular precursors for ACC, particularly those of IgA specificity, appearing in the tract after local challenge. The implications of these findings to infectious disease involving the urogenital tract are obvious and investigation of oral vaccines to control sexually transmitted disease as well as acquired urinary tract infections deserves further attention. There are further implications, however, for the understanding and management of male infertility. Copyright © 1992, Wiley Blackwell. All rights reserved
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1989 |
HUSBAND AJ, CLIFTON VL, 'ROLE OF INTESTINAL IMMUNIZATION IN URINARY-TRACT DEFENSE', IMMUNOLOGY AND CELL BIOLOGY, 67 371-376 (1989)
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