Associate Professor Vanessa Murphy

Physiologic changes during pregnancy have implications for both upper and lower airway function. Upper airway resistance increases, and total lung capacity decreases. Upper airway symptoms increase; some women develop pregnancy-induced rhinitis and there is an increased prevalence of sleep-disordered breathing compared to prepregnancy. Longitudinal studies examining changes in upper and lower airway function parameters are limited, particularly in women with asthma. Some studies have observed reduced lung function with advancing gestation; however, changes are small and unlikely to be of major clinical significance. Spirometry is therefore a useful tool for clinical assessment of women with asthma during pregnancy.

Background: Asthma affects 12.7% of pregnant women in Australia. Key recommendations for asthma management during pregnancy include: 4¿6 weekly review of lung function, medications, written asthma action plan, inhaler device technique, current asthma control and triggers; smoking cessation and vaccination advice. It is unknown if these key recommendations are provided to pregnant women with asthma in Australia. Aim: To explore usual antenatal asthma management (usual care) in Australia and the inclusion of key recommendations. Method: Pregnant women with asthma were invited to complete an online survey distributed in 2 antenatal clinics and via social media platforms from July 2017-Jan 2019. Results: The survey was completed by 142 pregnant women with asthma. 87(61%) were enrolled in an asthma management clinical trial and were therefore not receiving ¿usual¿ care. Data presented is from 55(39%) women receiving usual care at survey completion. Of these women, 36% did not have their asthma reviewed during their pregnancy, 31% had a written asthma action plan, 11% had lung function assessed, 38% had an asthma medication review and 35% had their inhaler technique reviewed. 65% were not questioned about their asthma symptoms, 85% were not asked about asthma triggers, 96% were not given information about vaccinations and 95% did not receive smoking cessation information. Conclusions: Overall, the key recommendations for antenatal asthma management were not always provided for this sample of pregnant women receiving usual care. Improved knowledge and implementation of these key recommendations by health professionals may alter this situation and improve maternal and infant outcomes.

Background: Given chronic disease is increasing among young women and unintended pregnancies among these women are associated with poor maternal and fetal outcomes, these women would benefit from effective preconception care. However, there is a lack of understanding of how these women use or don¿t use contraception to inform such interventions. This study examined patterns of contraceptive use among an Australian cohort of young women and investigated the influence of chronic disease on contraceptive use over time. Methods: Using data from 15,244 young women from the Australian Longitudinal Study on Women¿s Health (born 1989¿1995), latent transition analysis was performed to identify distinct contraceptive patterns among women who were at risk of an unintended pregnancy. Multinomial mixed-effect models were used to evaluate the relationship between contraceptive combinations and chronic disease. Results: Contraceptive use for women with cardiac and autoinflammatory diseases differed to women without chronic disease over the observation period. Compared to women without chronic disease using the pill, women with cardiac disease had double the odds of using ¿other¿ contraception and condoms (OR = 2.20, 95% CI 1.34, 3.59) and a modest increase in the odds of using the combined oral contraceptive pill and condoms (OR = 1.39, 95% CI 1.03, 1.89). Compared to women without chronic disease who used the pill, women with autoinflammatory disease had increased odds of using LARC and condoms (OR = 1.58, 95% CI 1.04, 2.41), using ¿other¿ contraception and condoms (OR = 1.69, 95% CI 1.11, 2.57), and using the¿combined oral contraceptive pill and condoms (OR = 1.38, 95% CI 1.09, 1.75). No differences in contraceptive patterns over the observation period were found for women with asthma or diabetes when compared to women without chronic disease. Conclusion: The findings identified a need for effective contraceptive counselling as part of routine chronic disease care and improved communication between health¿care providers and women with chronic disease to improve young women¿s contraceptive knowledge and agency in contraceptive choice, particularly for those with cardiac or autoinflammatory conditions. This may be the key to reducing high-risk unintended pregnancies among this vulnerable population.

Background: Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and information-seeking behaviours of women with asthma exposed to the 2019/2020 Australian fires, including women who were pregnant. Methods: Women with asthma were recruited from the Breathing for Life Trial in Australia. Following the landscape fire exposure period, self-reported data were collected regarding symptoms (respiratory and non-respiratory), asthma exacerbations, wellbeing, quality of life, information seeking, and landscape fire smoke exposure mitigation strategies. Participants¿ primary residential location and fixed site monitoring was used to geolocate and estimate exposure to landscape fire-related fine Particulate Matter (PM2.5). Results: The survey was completed by 81 pregnant, 70 breastfeeding and 232 non-pregnant and non-breastfeeding women with asthma. Participants had a median daily average of 17 µg/m3 PM2.5 and 105 µg/m3 peak PM2.5 exposure over the fire period (October 2019 to February 2020). Over 80% of participants reported non-respiratory and respiratory symptoms during the fire period and 41% reported persistent symptoms. Over 82% reported asthma symptoms and exacerbations of asthma during the fire period. Half the participants sought advice from a health professional for their symptoms. Most (97%) kept windows/doors shut when inside and 94% stayed indoors to minimise exposure to landscape fire smoke. Over two in five (43%) participants reported that their capacity to participate in usual activities was reduced due to prolonged smoke exposure during the fire period. Participants reported greater anxiety during the fire period than after the fire period (mean (SD) = 53(13) versus 39 (13); p < 0.001). Two in five (38%) pregnant participants reported having concerns about the effect of fire events on their pregnancy. Conclusion: Prolonged landscape fire smoke exposure during the 2019/2020 Australian fire period had a significant impact on the health and wellbeing of women with asthma, including pregnant women with asthma. This was despite most women taking actions to minimise exposure to landscape fire smoke. Effective and consistent public health messaging is needed during landscape fire events to guard the health of women with asthma.

Objective: Maternal asthma often complicates pregnancy and is linked with poorer quality of life. Additionally, individuals with asthma are at an increased risk of depression and anxiety. We examined whether asthma during pregnancy is related to parenting stress in the first year postpartum and if this relationship varies with level of asthma control. Methods: This cohort survey-based study included mothers with (n = 157) and without (n = 79) asthma. Mothers with asthma participated in this study following participation in a randomized controlled trial of a novel asthma management strategy during pregnancy. Mothers completed the Parenting Stress Index¿Short Form during the first 12 months postpartum. Mothers with asthma also completed the Asthma Control Questionnaire. Results: Parenting stress did not differ between mothers with and without asthma. Additionally, for mothers with asthma, there were no differences in levels of parenting stress based on asthma control. Conclusions: This study suggests that mothers with asthma are not at an increased risk for excessive parenting stress. However, due to response and sampling bias, levels of parenting stress in asthmatic mothers may be underreported in our sample.

Objective: Guidelines for asthma management contain a consensus recommendation that inhaled corticosteroid (ICS) dose should not be stepped down in pregnancy. However, this is not consistent with consumer preferences and pharmacological principles to minimize medication exposure during pregnancy. We investigated exacerbations after changes to ICS and long acting beta agonist (LABA) therapy in pregnant women with asthma. Methods: Pregnant women (n = 220) were recruited to a randomized controlled trial (RCT) where maintenance treatment was adjusted monthly based on either symptoms (control group), or fractional exhaled nitric oxide (FeNO, to alter ICS) and symptoms (to alter LABA, FeNO group). Exacerbations were monitored prospectively. Results: ICS were used by 137 (62.3%) women at some time during pregnancy. ICS dose remained unchanged in 16 women (11.7%, 95% confidence interval [CI] 7¿18%), increased in 37 women (27%, 95%CI 20¿35%), decreased in 34 women (24.8%, 95%CI 18%¿33%), or both increased and decreased in 50 women (36.5%, 95%CI 29¿45%). Exacerbations occurred within 14 days of ICS step-down in 11 women (13%, 95%CI 7.5%¿22%). This was not significantly different from exacerbations occurring within 14 days of step-up, in 7 women (8.1%, 95%CI 4%¿16%, P = 0.294). There were no differences between management groups. Exacerbations occurred within 14 days of step-down in 14.7% (95%CI 7%¿30%) of women in the control group, and in 12% (95%CI 6%¿24%) of women in the FENO group. Conclusions: ICS step-down could be considered when eosinophilic inflammation or symptoms are low, and may be a useful management approach for women, doctors, and midwives wishing to minimize ICS exposure during pregnancy.

Infants diagnosed with autism spectrum disorder (autism) have difficulty engaging in social communication and interactions with others and often experience language impairment. The use of infant-directed speech (IDS), which is the speech register used when interacting with infants, is associated with infant language and socio-communicative development. The aim of this study was twofold; the first aim was to scope the literature to determine if evidence exists for differences between the IDS caregivers use to infants at high-risk or those later diagnosed with autism, and the IDS typically spoken to neurotypical infants. The second aim was to investigate if any IDS characteristics used by caregivers of high-risk or diagnosed infant populations predicted language development. Twenty-six studies were included and provided evidence that high-risk and later diagnosed infants are exposed to similar amounts of IDS as their neurotypical peers. There is evidence, however, that the IDS used with high-risk and later diagnosed infants may comprise shorter utterances, more action-directing content, fewer questions, more attention bids, and more follow-in commenting. There is also evidence that more attention bids and follow-in commenting used to infants at high risk or those later diagnosed with autism were associated with better language abilities longitudinally.

Background: Children with a history of rhinovirus (RV) positive bronchiolitis have a high risk of developing subsequent asthma. Maternal asthma might also increase this risk. The aim of this study was to investigate the combined effects of hospitalization for RV positive bronchiolitis in infancy and a history of maternal asthma on the development of asthma at preschool age. Methods: This is a prospective cohort study of 139 preschool-aged children, with a history of hospital admission for bronchiolitis in infancy, followed-up to ascertain asthma and asthma-like symptoms, skin prick allergy test positivity, and lung function measured pre- and post-bronchodilator using impulse oscillometry. Results: Children with a past hospitalization for RV positive bronchiolitis (42.4% of all) and a history of maternal asthma (36.7% of all) had the greatest prevalence and risk ratio (RR) for doctor-diagnosed asthma (prevalence 81.8% and RR 2.10, 95% confidence interval [CI] 1.37¿3.19, p =.001), use of inhaled corticosteroids (68.2% and RR 2.17, 95% CI 1.19¿3.99, p =.001) and short-acting ß-agonists in the last 12 months (95.2% and RR 1.49, 95% CI 1.17¿1.89, p =.001), as compared to those with RV negative bronchiolitis and no maternal asthma history. More children in this group had an abnormal airway resistance (33.3% and adjusted risk ratio [aRR] 3.11, 95% CI 1.03¿9.47, p =.045) and reactance (27.8% and aRR 2.11, 95% CI 1.06¿4.26, p =.035) at 5 Hz, as compared to those with RV negative bronchiolitis and no maternal asthma history. Conclusion: Hospitalization for RV positive bronchiolitis in early life combined with a history of maternal asthma identifies a subgroup of children with a high asthma burden while participants with only one of the two risk factors had intermediate risk for asthma.

Objectives: Differences in the development of autistic children have been observed within the first year of life. Infant siblings of autistic children who are later diagnosed with autism themselves have differences in temperament, social communication, attention, and sensory and motor behaviors by 12¿months of age. However, less is known about the early development of other increased-likelihood groups. Some studies have identified that children born to mothers with asthma have a slightly elevated likelihood of autism. However, no studies have examined other aspects of their early development. Methods: Using a case series design, we profiled the temperament (Carey Temperament Scales), sensory (Sensory Profile 2), and global developmental features (Bayley-III) of seven Australian infants born to mothers with asthma who were screened to have an elevated likelihood of autism (First Year Inventory). Results: We found differences from the norms in temperament across the three timepoints (6¿weeks, 6¿months, and 12¿months), in the domains of rhythmicity, mood, persistence, and distractibility. Infants had typical sensory features at 6¿weeks and 6¿months; however, a sensory-sensitivity subtype was observed at 12¿months. Lastly, at 12¿months, cognitive skills were mostly typical, language skills were underdeveloped, and motor skills varied between infants. Conclusions: Results suggest that there may be a developmental profile indicative of an elevated likelihood of autism in infants born to mothers with asthma. However, due to the small sample size, these findings need to be considered with caution. Further research is needed to confirm diagnoses of autism in our sample.

Maternal asthma in pregnancy is associated with an increased risk of adverse perinatal outcomes. Adverse perinatal outcomes may result in poorer infant developmental outcomes, such as temperament and sensory difficulties. This study aimed to (1) assess differences in temperament and sensory features between infants born to mothers with and without asthma and (2) investigate differences in these infant behaviours as a function of maternal asthma severity and asthma control. Mothers completed the Carey Temperament Scales and the Sensory Profile 2 at either 6 weeks, 6 months, or 12 months postpartum. Overall, we observed no significant differences between infants born to mothers with and without asthma in their temperament or sensory features; scores in both domains fell within the normative range. More infants in the asthma group, however, were reported to be highly distractible. When compared with normative data, infants in both groups were reported to have poor predictability of biological functions and fewer infants engaged in low levels of sensory behaviours. Some infants were observed to experience difficulties with hyper-reactivity within several domains. Maternal asthma severity and control during pregnancy were not linked to significant differences between infant temperament and sensory features. The present findings indicate that infants born to mothers with asthma are not at an increased risk overall for temperament or sensory difficulties, compared to control infants. However, a subset of infants across both groups may be at risk for attention or sensory hyper-reactivity difficulties. Further research into the developmental outcomes of infants born to mothers with asthma is warranted.

Asthma and gestational diabetes mellitus are prevalent during pregnancy and associated with adverse perinatal outcomes. The risk of gestational diabetes mellitus is increased with asthma, and more severe asthma; yet, the underlying mechanisms are unknown. This review examines existing literature to explore possible links. Asthma and gestational diabetes mellitus are associated with obesity, excess gestational weight gain, altered adipokine levels and low vitamin D levels; yet, it¿s unclear if these underpin the gestational diabetes mellitus¿asthma association. Active antenatal asthma management reportedly mitigates asthma-associated gestational diabetes mellitus risk. However, mechanistic studies are lacking. Existing research suggests asthma management during pregnancy influences gestational diabetes mellitus risk; this may have important implications for future antenatal strategies to improve maternal-fetal outcomes by addressing both conditions. Addressing shared risk factors, as part of antenatal care, may also improve outcomes. Finally, mechanistic studies, to establish the underlying pathophysiology linking asthma and gestational diabetes mellitus, could uncover new treatment approaches to optimise maternal and child health outcomes.

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.

Low 25-hydroxyvitamin D (25(OH)D) levels are common in pregnancy and associated with adverse maternal/neonatal outcomes. In pregnant women with asthma, this study examined the association of lifestyle-and asthma-related factors on 25(OH)D levels and maternal/neonatal outcomes by vitamin D status. Serum 25(OH)D was measured at 16 and 35 weeks gestation in women with asthma (n = 103). Body mass index (BMI), gestational weight gain (GWG), smoking status, inhaled corticosteroid (ICS) use, asthma control, airway inflammation, and exacerbations, and maternal/neonatal outcomes were collected. Baseline and change (¿) in 25(OH)D were modelled separately using backward stepwise regression, adjusted for season and ethnicity. Maternal/neonatal outcomes were compared between low (25(OH)D < 75 nmol/L at both time points) and high (=75 nmol/L at one or both time points) vitamin D status. Fifty-six percent of women had low vitamin D status. Obesity was significantly associated with lower baseline 25(OH)D (Adj-R2 = 0.126, p = 0.008); ICS and airway inflammation were not. Excess GWG and season of baseline sample collection were significantly associated with ¿25(OH)D (Adj-R2 = 0.405, p < 0.0001); asthma-related variables were excluded (p > 0.2). Preeclampsia was more common in the low (8.6%) vs. high (0%) vitamin D group (p < 0.05). Obesity and excess GWG may be associated with gestational 25(OH)D levels, highlighting the importance of antenatal weight management.

Maternal asthma increases the risk of infant wheeze. Breastfeeding may offer protection but there is limited evidence in this high-risk group. We examined associations between breastfeeding and respiratory outcomes, in infants born to women with asthma. This study was a secondary analysis of two prospective cohorts of pregnant women with asthma, and their infants, conducted between 2007 and 2018. At 6 ± 1 (T1) and 12 ± 1 (T2) months post-partum, mothers reported breastfeeding patterns and infant wheeze (primary outcome), bronchiolitis, and related medication use and healthcare utilization, via a validated questionnaire; a subgroup completed face-to-face interviews. ¿2 tests and logistic regression models, adjusting for confounders, were utilized. Data were complete for 605 participants at T1 and 486 (80%) at T2. Of 605 participants: 89% initiated breastfeeding and 38% breastfed for more than 6 months. Breastfeeding for more than 6 months vs ¿never¿ was associated with a reduced adjusted relative risk of infant wheeze at T1 (0.54, 95% confidence interval, 0.30-0.96). Bronchiolitis risk was reduced at T1 and T2 with more tha 6 months of breastfeeding vs ¿never.¿ Breastfeeding duration of 1 to 3 months, 4 to 6 months, and more than 6 months were associated with a reduced risk of infant healthcare utilization (all P <.05, vs ¿never¿), but not medication use (P >.05). Breastfeeding for more than 6 months was associated with a reduced risk of wheeze, bronchiolitis, and wheeze-related healthcare utilization in infants at risk due to maternal asthma. Notably, breastfeeding for shorter durations was associated with a reduced risk of healthcare utilization compared with none. Larger cohorts are needed to further examine the impact of breastfeeding exposure on respiratory health in infants exposed to maternal asthma.

Background: The use of fractional exhaled nitric oxide (FeNO)-based asthma management during pregnancy can significantly reduce asthma exacerbations in non-smoking pregnant women. The feasibility of implementing this strategy into antenatal care has not been explored. Aims: To examine the feasibility of implementing FeNO-based asthma management into antenatal clinics in New South Wales (NSW) Australia. Materials and Methods: Semi-structured face-to-face interviews with video elicitation were conducted with healthcare professionals (HCPs) providing antenatal care in one of two hospital-based antenatal clinics in NSW, Australia. The video shown demonstrated the use of the FeNO instrument and other aspects of the management strategy, in antenatal care. Interviews were recorded, transcribed and analysed using qualitative content analysis. Results: A total of 20 interviews were conducted with 15 midwives, four obstetricians, and one general practitioner. Two main themes and ten sub-themes arose: Getting a number (sub-themes: engaging, technically easy, objective, predictive, reassuring); and Resourcing (sub-themes: time and timing, systems, staff, education and cost). Comments included: ¿It's easy, fast and effective¿ and ¿the main barrier is time¿. All HCPs felt capable of facilitating the FeNO-based management strategy, with appropriate education, and were willing to undertake this strategy, saying: ¿¿it would be perfectly acceptable for a midwife or doctor to do it¿; also, ¿they don't necessarily need to see a physician, it's something that midwives would take on generally¿¿. Conclusion: Participants in this study considered FeNO-based asthma management for pregnant women to be a feasible addition to antenatal care following appropriate provision of resources and education.

Background: Asthma affects approximately 12.7% of pregnant women in Australia. Increased maternal and infant morbidity is closely associated with poorly controlled asthma during pregnancy. Midwives are well placed to provide antenatal asthma management but data on current asthma management during pregnancy is not available, nor is the use of guidelines for clinical practice by this health professional group. Aim: To explore self-reported antenatal asthma management provided by midwives across Australia and how this reflects guideline recommendations. Method: An online survey was developed and distributed throughout Australia via the Australian College of Midwives, social media and healthcare facilities. Results: Responses from 371 midwives were obtained. Ten percent of midwives rated their knowledge as ¿good¿ and 1% as ¿very good¿, with 39% ¿poor¿ or ¿very poor¿. Being ¿somewhat¿ or ¿not at all¿ confident to provide antenatal asthma management was noted by 87% of midwives. Clinical guidelines were referred to by 50% of midwives and 40% stated that their main role was to refer women to other healthcare professionals. Only 54% reported that a clear referral pathway existed. Most respondents (>90%) recognised key recommendations for asthma management such as smoking cessation, appropriate vaccinations, and the continuation of prescribed asthma medications. Conclusion: Although midwives appear aware of key clinical recommendations for optimal antenatal asthma management, low referral to clinical practice guidelines and lack of knowledge and confidence was evident. Further research is required to determine what care pregnant women with asthma are actually receiving and identify strategies to improve antenatal asthma management by midwives.

Background and objective: The aim of this secondary analysis of a randomized controlled trial (RCT) of asthma management in pregnancy was to determine the treatment decision differences between a symptom control algorithm and a fractional exhaled nitric oxide (FENO)-guided algorithm, and whether the approach was effective in non-eosinophilic asthma (NEA). Methods: In this double-blind parallel group RCT, women with asthma were randomized prior to 22 weeks gestation to treatment adjustment according to a symptom control algorithm (control group), or a FENO-guided algorithm (inhaled corticosteroid (ICS) dose adjusted according to FENO with long-acting beta-agonist (LABA) added for uncontrolled symptoms). NEA was classified as baseline blood eosinophils <0.26 × 109/L and FENO =29 ppb. Exacerbations requiring medical intervention were recorded. Results: Among 220 non-smokers (n = 109 control, n = 111 FENO), 1006 treatment decisions were made, with significant group differences after the first and second algorithm applications. 53% of women had NEA. Treatment was better targeted to phenotype in the FENO group: ICS use increased in eosinophilic asthma (EA, 48¿86%), while ICS/LABA increased in NEA (11¿30%). Fewer women in the FENO group had exacerbations during pregnancy in NEA only (18.9% FENO vs 44% control, P = 0.006). Conclusion: The FENO algorithm was more effective in treating NEA, resulting in reduced exacerbations, compared to a symptom control algorithm. This was not the result of ICS overtreatment, since the benefits occurred at a lower median daily ICS dose. Two applications of the FENO-guided algorithm, one month apart, were sufficient to achieve beneficial effects in terms of asthma exacerbations, among pregnant women with asthma.

Measurement of vitamin D status has significant use in clinical and research settings, including during pregnancy. We aimed to assess the agreement of total 25-hydroxyvitamin D (25(OH)D) concentration, and its three analytes (25-hydroxyvitamin D3 (25(OH)D3 ), 25-hydroxyvitamin D2 (25(OH)D2 ) and Epi-25-hydroxyvitamin D3 (Epi-25(OH)D3 )), in plasma and serum samples collected during pregnancy, and to examine the proportion of women who change vitamin D status category based on sample type. Matching samples were collected from n = 114 non-fasting women between 12¿25 weeks gestation in a clinical trial in Newcastle, Australia. Samples were analysed by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to quantify total 25(OH)D and its analytes and examined using Bland-Altman plots, Pearson correlation (r), intraclass correlation coefficient and Cohen¿s Kappa test. Serum total 25(OH)D ranged from 33.8¿169.8 nmol/L and plasma ranged from 28.6¿211.2 nmol/L. There was a significant difference for total 25(OH)D based on sample type (measurement bias 7.63 nmol/L for serum vs plasma (95% Confidence Interval (CI) 5.36, 9.90, p = 0.001). The mean difference between serum and plasma concentrations was statistically significant for 25(OH)D3 (7.38 nmol/L; 95% CI 5.28, 9.48, p = 0.001) and Epi-25(OH)D3 (0.39 nmol/L; 95% CI 0.14, 0.64, p = 0.014). Of 114 participants, 28% were classified as vitamin D deficient (<50 nmol/L) or insufficient (<75 nmol/L) based on plasma sample and 36% based on serum sample. Nineteen (16.7%) participants changed vitamin D status category based on sample type. 25-hydroxyvitamin D quantification using LC-MS/MS methodology differed significantly between serum and plasma, yielding a higher value in plasma; this influenced vitamin D status based on accepted cut-points, which may have implications in clinical and research settings.

Objective: We aimed to examine the prevalence and severity of psychological distress of women with asthma in both the prenatal and postnatal periods, and to determine whether asthmatic women with and without mental health problems differ in self-management, medications knowledge, and asthma symptoms. Methods: We assessed spirometry performance and asthma symptoms in 120 women (mean age 29.8 years) before 23 weeks gestation, as part of the Breathing for Life Trial (Trial ID: ACTRN12613000202763). Prenatal depression data was obtained from medical records. At 6 weeks postpartum, we assessed general health, self-reported asthma control, depression symptoms (with the Edinburgh Postnatal Depression Scale) and adaptive functioning (with the Achenbach System of Empirically Based Assessment scales). Results: Twenty percent of our sample reported having a current mental health diagnosis, 14% reported currently receiving mental health care, while 47% reported having received mental health care in the past (and may/may not have received a diagnosis). The sample scored high on the Aggressive Behavior, Avoidant Personality, and Attention Deficit/Hyperactivity scales. Poorer self-reported postnatal asthma control was strongly correlated with elevated somatic complaints, externalizing problems, antisocial personality problems, and greater withdrawal. Prenatal spirometry or asthma severity and control were largely not associated with measures of psychopathology. Conclusions: These findings indicate that pregnant women with asthma frequently report issues with psychopathology during the prenatal and postnatal periods, and that the subjective perception of asthma control may be more related to psychopathology than objective asthma measures. However, due to sample bias, these findings are likely to be understated.

Background: Maternal asthma is associated with perinatal complications and respiratory illness in offspring. Obesity increases asthma exacerbation risk in pregnancy and risk of wheeze in offspring. Objectives: In this secondary analysis of a randomized controlled trial, we investigated the influence of maternal body mass index, gestational weight gain (GWG), and fractional exhaled nitric oxide (FENO)-based management on asthma exacerbations in pregnancy and offspring wheeze. Methods: A total of 220 women were randomized to asthma treatment adjustment according to symptoms (control group), or FENO and symptoms (FENO group). Exacerbations were recorded prospectively. Height and weight were measured at baseline, and in late pregnancy. GWG was categorized according to Institute of Medicine guidelines. A validated parent-completed questionnaire assessed infant wheeze-related outcomes. Results: FENO-based management was associated with a significantly lower incidence rate ratio for maternal exacerbations in nonobese mothers (0.52, 95% confidence interval [CI], 0.31-0.88, P = .015, n = 129), and women with GWG within recommendations (0.35, 95% CI, 0.12-0.96, P = .042, n = 43), but not for obese mothers (0.59, 95% CI, 0.32-1.08, P = .089, n = 88), or women with excess GWG (0.58, 95% CI, 0.32-1.04, P = .07, n = 104). Recurrent bronchiolitis occurred in 5.3% (n = 1) of infants born to non-overweight mothers, 16.7% (n = 3) of infants of overweight mothers, and 21.7% (n = 5) of infants of obese mothers in the control group. In the FENO group, 2 infants of obese mothers had recurrent bronchiolitis (7.1%, P = .031). Conclusions: The benefits of FENO-based management are attenuated among obese mothers and those with excess GWG, indicating the importance of weight management in contributing to improved asthma management in pregnancy.

Background: Studies demonstrate the prescription rate for inhaled corticosteroids (ICS) decreases in early pregnancy, possibly increasing exacerbation risk. This could be related to non-adherence to prescribed asthma medication or medication cessation by the patient or doctor. ICS use during pregnancy has not previously been summarized in a systematic review. Objective: The aim of this systematic review and meta-analysis was to evaluate the use of ICS during pregnancy among asthmatic women, specifically: (1) the prevalence of use, (2) changes of use during pregnancy compared with pre-pregnancy and (3) medication adherence among ICS users. Methods: We systematically searched literature in Embase, MEDLINE, CINAL and Cochrane, using terms related to asthma, pregnancy and medication use. All English articles reporting ICS among pregnant women with asthma were included. Prevalence, changes in ICS use during pregnancy and ICS adherence were pooled using STATA (version 15.0, StataCorp USA). Results: A total of 4237 references were retrieved in the initial search. Screening and review led to the inclusion of 52 articles for one or more aims (Aim 1: N¿=¿45; Aim 2, N¿=¿13; and Aim 3, N¿=¿5). The pooled prevalence of ICS use during pregnancy was 41% (95%CI 36%-45%); 49% (95%CI 44%-55%) in Europe, 39% (95%CI 32%-47%) in Australia and 34% (95%CI 27%-41%) in North America. In eight prescription databases, ICS prescription rates lowered in the first trimester of pregnancy, compared with pre-pregnancy, increased in the second trimester and decreased in the third trimester. Five studies reported ICS adherence among pregnant women, using four measures of self-reported non-adherence. In two comparable studies, pooled ICS non-adherence was 40% (95%CI 36%-44%). Conclusions: The prevalence of ICS use among pregnant women with asthma is 41% and varies widely between countries and continents, and prescription rates for ICS change throughout pregnancy. More studies are needed to investigate ICS adherence during pregnancy in women with asthma.

Background: Vitamin D may influence pregnancy and infant outcomes, especially infant respiratory health. This study aimed to examine vitamin D status in pregnant women with asthma, and whether higher vitamin D levels are associated with fewer adverse respiratory outcomes in their infants. Methods: Pregnant women with asthma, recruited from John Hunter Hospital Newcastle Australia (latitude 33°S), had serum total 25-hydroxyvitamin-D (25(OH)D) measured at 16 and 35 weeks gestation. Infant respiratory outcomes were collected at 12 months by parent-report questionnaire. Mother¿infant dyads were grouped by serum 25(OH)D during pregnancy: 25(OH)D < 75 nmol/L (at both time-points) versus 25(OH)D = 75 nmol/L (at one or both time-points). Results: In 52 pregnant women with asthma, mean serum 25(OH)D levels were 61 (range 26¿110) nmol/L at 16 weeks, and 65 (range 32¿116) nmol/L at 35 weeks, gestation. Thirty-one (60%) women had 25(OH)D < 75 nmol/L at both time-points; 21 (40%) had 25(OH)D = 75 nmol/L at one or both time-points. Maternal 25(OH)D < 75 nmol/L during pregnancy was associated with a higher proportion of infants with ¿wheeze ever¿ at 12 months, compared with 25(OH)D = 75 nmol/L (71 versus 43%, p =.04). Infant acute-care presentations (45 versus 13%, p =.02) and oral corticosteroid use (26 versus 4%, p =.03) due to ¿asthma/wheezing¿ were higher in the maternal group with 25(OH)D < 75 nmol/L, versus =75 nmol/L. Conclusions: Most pregnant women with asthma had low vitamin D status, which persisted across gestation. Low maternal vitamin D status was associated with greater risk of adverse respiratory outcomes in their infants, a group at high risk of developing childhood asthma.

This paper compares how rules of international humanitarian law and rules of Islamic law protect children in armed conflict. It examines areas of convergence and divergence, and areas where there is room for clarification between these two legal systems. This comparative exercise spotlights four key topics marking the wartime experience of children: the unlawful recruitment and use of children by armed forces and armed groups, the detention of children, their access to education, and the situation of children separated from their families.

Purpose of reviewAsthma affects up to 13% of pregnancies worldwide and has a varying and unpredictable clinical course during pregnancy. Pharmacological asthma treatment is recommended; however, studies show that some pregnant women with asthma cease their medication in early pregnancy. There is likely a large unmet disease burden arising from asthma in pregnancy.Recent findingsAntenatal and asthma guidelines lack sufficient information on asthma management in pregnant women, and implementation of the current guidelines seems inadequate. Prescription databases provide evidence of cessation of asthma medication during pregnancy on a population level. Population-based databases also provide evidence of rare adverse perinatal outcomes. The risk of childhood asthma in the offspring of women with asthma is reduced by adequate control of maternal asthma during pregnancy. Vitamin D sufficiency during pregnancy could also reduce the risk of childhood asthma.SummaryThe findings of this review demonstrate the need for improved asthma and antenatal guidelines regarding asthma management during pregnancy, and the need of adequate implementation of these guidelines. Furthermore, adequate asthma control during pregnancy is needed to reduce the risk of childhood asthma. To maintain asthma control, prepregnancy medication should be continued throughout pregnancy and adjusted according to the current treatment steps if required.

Objective: Maternal asthma during pregnancy is associated with a higher risk of negative perinatal outcomes. However, little is known about the direct effects of maternal asthma on infant cognitive development. We examined the evidence for an impact of maternal asthma during pregnancy on cognitive and behavioral development of the child. Data sources: We conducted a MEDLINE, PsychINFO, and manual search of the databases for all available studies until January 9th, 2018. Study Selections: Studies were deemed relevant if they included child cognitive and behavioral development as the outcome, with maternal asthma as the determinant of interest. Results: Ten articles matched selection criteria. Some studies report that maternal asthma is associated with increased risk for autism and intellectual disability in children. However, these effects are small and are often eliminated when controlling for confounding variables. Other studies have found no association. The only prospective study found that well-managed asthma during pregnancy was not associated with negative developmental outcomes in children. Conclusions: The evidence suggests that the relationship between maternal asthma during pregnancy and poor developmental and behavioral outcomes of children is weak. Children of mothers with well-managed asthma during pregnancy have similar developmental trajectories to those born to healthy mothers. Prospective, longitudinal studies are needed to confirm these conclusions. Optimal asthma management is important in pregnancy as it may have longer term benefits for the health of the offspring. As the rate of asthma increases in the population, the implications of maternal asthma on child development will be of greater importance.

Background: The single-center double-blind, randomized controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FENO) in combination with asthma symptoms (FENO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (Australian New Zealand Clinical Trials Registry, no. 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FENO group. However, the effect of FENO-guided management on the development of asthma in the offspring is unknown. Objective: We sought to investigate the effect of FENO-guided asthma management during pregnancy on asthma incidence in childhood. Methods: A total of 179 mothers consented to participate in the Growing into Asthma (GIA) double-blind follow-up study with the primary aim to determine the effect of FENO-guided asthma management on childhood asthma incidence. Results: A total of 140 children (78%) were followed up at 4 to 6 years of age. FENO-guided as compared to symptoms-only approach significantly reduced doctor-diagnosed asthma (25.9% vs 43.2%; odds ratio [OR], 0.46, 95% CI, 0.22-0.96; P =.04). Furthermore, frequent wheeze (OR, 0.27; 95% CI, 0.09-0.87; P =.03), use of short-acting ß-agonists (OR, 0.49; 95% CI, 0.25-0.97; P =.04), and emergency department visits for asthma (OR, 0.17; 95% CI, 0.04-0.76; P =.02) in the past 12 months were less common in children born to mothers from the FENO group. Doctor-diagnosed asthma was associated with common risk alleles for early onset asthma at gene locus 17q21 (P =.01 for rs8069176; P =.03 for rs8076131), and higher airways resistance (P =.02) and FENO levels (P =.03). A causal mediation analysis suggested natural indirect effects of FENO-guided asthma management on childhood asthma through ¿any use¿ and ¿time to first change in dose¿ of inhaled corticosteroids during the MAP trial (OR: 0.83; 95% CI: 0.59-0.99, and OR: 0.90; 95% CI: 0.70-1.03, respectively). Conclusions: FENO-guided asthma management during pregnancy prevented doctor-diagnosed asthma in the offspring at preschool age, in part mediated through changes in use and dosing of inhaled corticosteroids during the MAP trial.

Background: Asthma affects 12.7% of pregnancies in Australia. Poorly controlled asthma is associated with increased maternal and infant morbidity and mortality. Optimal antenatal management of asthma during pregnancy has the potential to reduce complications relating to asthma. Evidence-based clinical practice guidelines help to translate health research findings into practice and when implemented can improve health outcomes. National and International guidelines currently provide recommendations for optimal asthma care in pregnancy. Aim: To appraise the existing asthma in pregnancy guidelines with respect to their evidence for recommendations, consistency of recommendations and appropriateness for clinical practice. Method: The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to appraise four English language asthma in pregnancy guidelines, published or updated between 2007 and 2016. The recommendations, range and level of evidence was analysed. Results: Two of the four guidelines scored highly in most domains of the appraisal. Many of the recommendations made in the appraised guidelines were consistent. Due to the lack of randomised controlled trials involving pregnant women with asthma, most recommendations were evidenced by consensus and expert opinion rather than high quality meta-analysis, systematic reviews of randomised controlled trials. Conclusion: The recommended antenatal asthma management was generally consistent among the guidelines but lacked clarity in some areas which then leave them open to interpretation. More randomised controlled trials involving pregnant women with asthma are required to fortify the recommendations made and asthma management guidelines should be included in Australian Antenatal Care Guidelines as they currently are not.

Background Obesity is a risk factor for exacerbations of asthma, but the mechanisms of this effect in pregnancy are unknown. Objective This study determined the influence of maternal body mass index, gestational weight gain, eosinophilic inflammation, and systemic macrophage activation on the risk of exacerbations during pregnancy. Methods Women with asthma (n = 164) participated in the study. Body mass index recorded at baseline (17 weeks gestation) was categorized as healthy weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (>30 kg/m2). Exacerbations requiring medical intervention were recorded prospectively. Asthma control, medication use, and fractional exhaled nitric oxide were assessed monthly; additional visits occurred during exacerbations. Peripheral blood was collected at baseline for the measurement of eosinophils, soluble CD-163, C-reactive protein, and IL-6. Results Exacerbations occurred in a higher proportion of overweight (51.1%) and obese (48.4%) women compared with healthy weight women (25%; P =.026). Excess weight gain during pregnancy was not associated with exacerbation risk. Macrophage activation (elevated serum soluble CD-163) was associated with exacerbations requiring oral corticosteroids (P =.043), whereas high peripheral blood eosinophils or fractional exhaled nitric oxide were not associated with exacerbation or oral corticosteroid use. Conclusions Being overweight or obese confers a greater risk of asthma exacerbation during pregnancy, and may be due to systemic macrophage activation.

International guidelines recommend a collaborative approach to the care of pregnant women with asthma. Midwives, as the primary health care provider for childbearing women should be viewed as collaborative partners in the provision of antenatal asthma management. However, the role of the midwife in providing antenatal asthma management has not been widely reported.Method: Australian midwives' perceived role in antenatal asthma management was studied using a qualitative descriptive method. Semi-structured in-depth interviews were conducted with 13 midwives working in a regional tertiary hospital. Morse and Field's four-stage process was used to analyse the data.Findings: the perceived role of the midwife in antenatal asthma management varied among participants. Some midwives stated their role was to refer women on to other health professionals. Other midwives stated that they should provide education to the women regarding their asthma management during their pregnancy.Conclusion: participants were uncertain about their role and lacked confidence in antenatal asthma management. The midwifery context in which they worked and the resources available to them at this health care facility appeared to influence the perception of their role.

Pregnancy is a unique state requiring alterations in maternal physiology to accommodate the growing fetus. Whilst the maternal immune system is normally well adept at performing this task, the presence of immune disorders, such as asthma, often lead to pregnancy-related complications affecting both mother and baby. Australia has a high prevalence of asthma; with approximately 12% of pregnant women reported to have current asthma. Poor control of asthma is of far greater risk than the use of asthma medications. Being able to identify complications associated with asthma during pregnancy is of great importance in providing appropriate asthma management and medical care to these pregnant women, which may have lifelong consequences for their offspring.

Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function. Acetate increases acetylation at the Foxp3 promoter, likely through HDAC9 inhibition. Epigenetic effects of fibre/acetate in adult mice led us to examine the influence of maternal intake of fibre/acetate. High-fibre/acetate feeding of pregnant mice imparts on their adult offspring an inability to develop robust AAD. High fibre/acetate suppresses expression of certain genes in the mouse fetal lung linked to both human asthma and mouse AAD. Thus, diet acting on the gut microbiota profoundly influences airway responses, and may represent an approach to prevent asthma, including during pregnancy.

Asthma is a common comorbidity during pregnancy and its prevalence is increasing in the com- munity. Exacerbations are a major clinical problem during pregnancy with up to 45% of women needing to seek medical help, resulting in poor outcomes for mothers and their babies, including low birth weight and preterm delivery. The goals of effective asthma management in pregnancy are to maintain the best possible asthma control and prevent exacerbations. This is achieved by aiming to prevent day- and night-time symptoms, and maintain lung function and normal activity. In addition, maintaining fetal oxygenation is an important consideration in pregnancy. Guide- lines recommend providing asthma advice and review prior to conception, and managing asthma actively during pregnancy, with regular 4-weekly review, provision of a written action plan, use of preventer medications as indicated for other adults with asthma, and management of comorbid conditions such as rhinitis. Improvements have been made in recent years in emergency department management of asthma in pregnancy, and multidisciplinary approaches are being proposed to optimise both asthma outcomes and perinatal outcomes. One strategy that has demonstrated success in reducing exacerbations in pregnancy is treatment adjustment using a marker of eosinophilic lung inflammation, the exhaled nitric oxide fraction (FeNO). The use of an algorithm that adjusted inhaled corticosteroids (ICS) according to FeNO and added long-acting ß-agonists when symptoms remained uncontrolled resulted in fewer exacerbations, more women on ICS but at lower mean doses, and improved infant respiratory health at 12 months of age. Further evidence is needed to determine whether this strategy can also improve perinatal outcomes and be successfully translated into clinical practice.

Pregnancy provides a unique challenge for maternal immunity, requiring the ability to tolerate the presence of a semi-allogeneic foetus, and yet still being capable of inducing an immune response against invading pathogens. To achieve this, numerous changes must occur in the activity and function of maternal immune cells throughout the course of pregnancy. Respiratory viruses take advantage of these changes, altering the sensitive balance of maternal immunity, leaving the mother with increased susceptibility to viral infections and increased disease severity. Influenza virus is one of the most common respiratory virus infections during pregnancy, leading to an increased risk of ICU hospitalisations, pneumonia, acute respiratory distress syndrome and even death. Whilst much research has been performed to understand the changes that must take place in maternal immunity during pregnancy, considerable work is still needed to fully comprehend this tremendous feat. To date, few studies have focused on the alterations that occur in maternal immunity during respiratory virus infections. This review highlights the role of dendritic cells (DCs) and CD8 T cells during pregnancy, and the changes that occur in these antiviral cells following influenza virus infections.

International guidelines indicate that management of asthma during pregnancy should be multidisciplinary; however, the role of midwives has not been researched. Method: A qualitative descriptive study exploring Australian midwives' current knowledge about asthma in pregnancy and their perceived role in antenatal asthma management was conducted, involving individual semi-structured in-depth interviews with 13 midwives in a tertiary referral hospital. Data were analysed using Morse and Field's four-stage process. Findings: Midwives identified barriers preventing them from providing antenatal asthma management, including: lack of knowledge about asthma in pregnancy; time constraints; women's knowledge about asthma in pregnancy; lack of a clear referral pathway; and lack of accessible asthma management equipment. Barriers were influenced by the institutional context in which the midwives worked. Conclusion: While participants identified barriers preventing them from providing recommended antenatal asthma management, they also suggested that improving their knowledge about asthma in pregnancy and developing a clear referral pathway may be beneficial.

© 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.

© 2015 Taylor & Francis. Objective: To investigate the relationship between asthma control and psychosocial outcomes in pregnant women with asthma. Methods: Secondary analysis (N¿=¿221) of a randomized controlled trial of treatment adjustments, based on fractional exhaled nitric oxide versus clinical guideline-based algorithms. Psychosocial variables included generic and asthma-specific quality of life (SF12, AQLQ-M), illness perceptions (BIPQ), perceived control (PCAQ), perceived risk of side effects (PRSE) and anxiety (STAI-6). Asthma control was defined as controlled (Asthma Control Questionnaire (ACQ7)¿=1.5 at randomization and end of study), improved (ACQ7¿>¿1.5 at randomization and =1.5 at end of study) and unimproved (ACQ7¿>1.5 at end of study). Regression models were fitted for each psychosocial measure at the end of the study, with adjustment for baseline values and smoking status, with predictor variable asthma control. Results: Women with unimproved asthma had poorer physical (SF12, p¿=¿0.012) and asthma-specific quality of life across all domains (AQLQ-M, p¿=¿0.012) compared to women with controlled asthma. They believed that they had less control over their asthma (PCAQ total p¿=¿0.014), had more symptoms and that their illness had a greater effect on their emotions and their lives in general (BIPQ identity, consequences, concern, emotional response p¿=¿0.015). Women with improved asthma control had significantly lower AQLQ-M breathlessness (p¿=¿0.048) and lower total scores (p¿=¿0.04) than women with controlled asthma. Conclusions: Pregnant women who are not able to get control of their asthma symptoms may experience worse quality of life and are likely to have more negative perceptions about their condition.

Background: Congenital thoracic malformations (CTM) are rare lung lesions that are managed with surgical resection or active surveillance. Methods: Nitrogen lung clearance index (LCI), reactance and resistance (X5Hz and R5Hz), forced expiratory volume in 1 s and forced vital capacity (FEV1 and FVC) were prospectively measured in 10 children with CTM (mean age/SD: 7.6/1.3) who had undergone surgical resection in early life and in 17 healthy children (mean age/SD: 4.8/0.4). Total lung capacity (TLC) was also conducted in children older than 7 years of age with CTM (n = 8). Results: Mean LCI was 8.0 (95% CI 7.5 to 8.5) in the CTM group and 7.3 (95% CI 7.0 to 7.6) in healthy children (p = 0.016). Mean X5Hz was -0.44kPa/l/s (95% CI -0.58 to -0.31) in the CTM group and -0.31kPa/l/s (95% CI -0.35 to -0.27) in healthy children (p = 0.02). Mean Z score for X5Hz was -2.11 (95% CI -3.59 to -0.63) in the CTM group and -0.11 (95% CI -0.55 to 0.33) in healthy children (p = 0.0008). Mean FEV1 was 1.21 L (95% CI 0.97 to 1.45) in the CTM group and 1.02 L (95% CI 0.90 to 1.15) in healthy children (p = 0.22). Mean % predicted FEV1 was 83% (95% CI 74 to 92) in the CTM group and 97% (95% CI 87 to 107) in healthy children (p < 0.05). Mean % predicted TLC in CTM children was 121.3% (95% CI 88.45 to 154.1). Mean LCI was inversely correlated with height z-scores in the CTM group (rs = -0.88, p = 0.002) but not in healthy children (rs = 0.22, p = 0.4). Conclusions: Children with CTM have impaired lung function as demonstrated by the significant differences in LCI, reactance and FEV1 but not FVC, resistance and TLC. These findings may be of clinical relevance as ventilation inhomogeneities are closely correlated with somatic growth in this study.

Objective Maternal asthma is the most common chronic disease complicating pregnancy and is a risk factor for bronchiolitis in infancy. Recurrent episodes of bronchiolitis are strongly associated with the development of childhood asthma. Methods We conducted a follow-up study of infants born to women with asthma who completed a double-blind randomised controlled trial during pregnancy. In this trial, pregnant women with asthma were assigned to treatment adjustment by an algorithm using clinical symptoms (clinical group) or the fraction of exhaled nitric oxide (FeNO group) and we showed that the FeNO group had significantly lower asthma exacerbation rates in pregnancy. Results 146 infants attended the 12-month follow-up visit. Infants born to mothers from the FeNO group were significantly less likely to have recurrent episodes of bronchiolitis in the first year of life (OR 0.08, 95% CI 0.01 to 0.62; p=0.016) as compared with the clinical group. Conclusions Optimised management of asthma during pregnancy may reduce recurrent episodes of bronchiolitis in infancy, which could potentially modulate the risk to develop or the severity of emerging childhood asthma.

Background: There are few studies investigating the relationship between respiratory viral infection in pregnancy and asthma in the offspring, and none among mothers with asthma. Infants of mothers with asthma are more likely to wheeze and have a higher risk of developing asthma than infants of non-asthmatic mothers. Methods: A prospective cohort study of viral infection in pregnancy was conducted between 2007 and 2009, and a subgroup of infants of mothers with asthma was followed up at 6 and 12 months of age. During common colds, nasal and throat swabs were collected from mothers and respiratory viruses detected by polymerase chain reaction. Respiratory health of infants was assessed by parent-completed questionnaire. Results: Twelve-month-old infants whose mothers had confirmed viral infections in pregnancy (n = 26) reported more frequent wheeze (40% had 4-12 wheeze attacks compared with 0%), sleep disturbed by wheeze (1 night per week or more in 60% vs. 11%), beta agonist treatment for wheeze (27% vs. 0%), prolonged colds (2 wk or longer 31% vs. 0%), more eczema (40% vs. 6.3%), and parent-perceived asthma (32% vs. 0%), compared with infants whose mothers had common colds without laboratory-confirmed viral infection (n = 16). Conclusions: This study demonstrates a relationship between maternal respiratory viral infection in pregnancy and wheezing illness in infants of mothers with asthma. Viral infections are the most common cause of asthma exacerbations in pregnancy, and infants of asthmatic mothers are at increased risk of asthma themselves. Further research is needed to elucidate the mechanisms involved. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Asthma commonly occurs in pregnant females, and recent data have outlined the risks of adverse perinatal outcomes among this population. There is an increased risk of low birth weight and small for gestational age, particularly among females with moderate-to-severe asthma and exacerbations during pregnancy. There is also an increased risk of preterm birth, especially with oral steroid use, a small but statistically significant increased risk of congenital malformations, particularly of cleft lip with or without cleft palate, and an increased risk of neonatal hospitalisation and death. Active management may reduce these risks, possibly through reductions in exacerbations. Additional reassuring data have been presented for asthma medication use, which support the benefits outweighing the risks of indicated asthma medication use in pregnancy. Viral infections are an important trigger of asthma exacerbations in pregnancy, and recent data provides possible immunological changes that may explain this. Poor medication adherence despite worsening asthma symptoms in pregnancy is a problem which continues to be demonstrated in the literature. Improving asthma control in pregnancy has the potential to improve not only the mother's health but also that of her child. © ERS 2014.

The rising prevalence of asthma and atopic disease in industrialized countries in the last 50 years has raised important questions about how and why the disease develops in susceptible populations. Most asthma begins in childhood in association with allergic sensitization and the development of a TH2 phenotype. It is recognized that asthma arises in the context of a complex interaction between genetic factors and the evolving immune system of the infant and the environment to which it is exposed, which now includes its in utero exposure. Early life exposures that lead to allergen sensitization and airway damage, especially in the form of viral respiratory tract infections, may lead to disease induction that commence the process that leads in some to asthma. Asthma models and early life observations suggest that repeated exposure to allergens and viral infection perpetuate a state of chronic airway inflammation leading to a maladaptive innate immune response that fails to resolve, characterized by chronic airway inflammation, airway remodeling and airway hyperresponsiveness. This article will concentrate on the development of asthma in the context of early life and maternal influences, including the effect of asthma on both the fetus and the mother. © 2014 Informa UK Ltd.

Background Asthma is a complex disease that involves both genetic factors and environmental exposures. Aberrant epigenetic modifications, such as DNA methylation, may be important in asthma development. Fetal exposure to maternal asthma during critical periods of in utero development may lead to epigenetic alterations that predispose infants to a greater risk of developing asthma themselves. We investigated alterations in the DNA methylation profile of peripheral blood from infants exposed to maternal asthma during pregnancy. Methods Peripheral blood was collected from 12-month-old infants born to women with (n = 25) and without (n = 15) doctor diagnosed asthma during pregnancy. Genomic DNA was extracted, bisulfite converted, and hybridized to Infinium Methylation 27 arrays (Illumina), containing over27,000 CpGs from 14,495 genes. CpG loci in only autosomal genes were classified as differentially methylated at the 99% level (P < 0.01, |DiffScore| > 22 and delta beta >0.06). Results There were 70 CpG loci, corresponding to 67 genes that were significantly differentially methylated. Twelve CpG loci (11 genes) showed greater than 10% comparative difference in DNA methylation, including hyper-methylated loci of FAM181A, MRI1, PIWIL1, CHFR, DEFA1, MRPL28, AURKA, and hypo-methylated loci of NALP1L5, MAP8KIP3, ACAT2, and PM20D1 in maternal asthma. Methylation of MAPK8IP3 was significantly negatively correlated with maternal blood eosinophils (r = -0.38; P = 0.022), maternal eNO (r = -0.44; P = 0.005), and maternal serum total IgE (r = -0.39, P = 0.015). Methylation of AURKA negatively correlated with maternal hemoglobin (r = -0.43; P = 0.008), infants height (r = -0.51; P < 0.001) and weight (r = -0.36; P = 0.021). Methylation of PM20D1 was lower in infants born to mothers with asthma on inhaled corticosteroid treatment. Methylation of PM20D1 was lower and MRI1 was higher in infants born to atopic mothers without asthma. Conclusions In an Australian study population, exposure to maternal asthma during pregnancy is associated with differential methylation profiles of infants' peripheral blood DNA, which may act as risk factors for future asthma development. © 2013 Wiley Periodicals, Inc.

Objective: To investigate if maternal asthma is associated with an increased risk of maternal and placental complications in pregnancy. Methods: Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). Cohort studies published between January 1975 and March 2012 were considered for inclusion. Forty publications met the inclusion criteria, reporting at least one maternal or placental complication in pregnant women with and without asthma. Relative risk (RR) with 95% confidence intervals (CIs) was calculated. Results: Maternal asthma was associated with a significantly increased risk of cesarean section (RR=1.31, 95%CI=[1.22-1.39]), gestational diabetes (RR=1.39, 95%CI=[1.17-1.66]), hemorrhage (antepartum: RR=1.25, 95%CI=[1.10-1.42]; postpartum: RR=1.29, 95%CI=[1.18-1.41]), placenta previa (RR=1.23, 95%CI=[1.07-1.40]), placental abruption (RR=1.29, 95%CI=[1.14-1.47]) and premature rupture of membranes (RR=1.21, 95%CI=1.07-1.37). Moderate to severe asthma significantly increased the risk of cesarean section (RR=1.19, 95%CI=[1.09-1.31]) and gestational diabetes (RR=1.19, 95%CI=[1.06-1.33]) compared to mild asthma. Bronchodilator use was associated with a significantly lowered risk of gestational diabetes (RR=0.64, 95%CI=[0.57-0.72]). Conclusions: Pregnant women with asthma are at increased risk of maternal and placental complications, and women with moderate/severe asthma may be at particular risk. Further studies are required to elucidate whether adequate control of asthma during pregnancy reduces these risks. © 2014 Informa UK Ltd. All rights reserved.