Dr Yogavijayan Kandasamy

Background: Machine learning has been attracting increasing attention for use in healthcare applications, including neonatal medicine. One application for this tool is in understanding and predicting neurodevelopmental outcomes in preterm infants. In this study, we have carried out a systematic review to identify findings and challenges to date. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases were searched in February 2022, with articles then screened in a non-blinded manner by two authors. Results: The literature search returned 278 studies, with 11 meeting the eligibility criteria for inclusion. Convolutional neural networks were the most common machine learning approach, with most studies seeking to predict neurodevelopmental outcomes from images and connectomes describing brain structure and function. Studies to date also sought to identify features predictive of outcomes; however, results varied greatly. Conclusions: Initial studies in this field have achieved promising results; however, many machine learning techniques remain to be explored, and the consensus is yet to be reached on which clinical and brain features are most predictive of neurodevelopmental outcomes. Impact: This systematic review looks at the question of whether machine learning can be used to predict and understand neurodevelopmental outcomes in preterm infants.Our review finds that promising initial works have been conducted in this field, but many challenges and opportunities remain.Quality assessment of relevant articles is conducted using the Newcastle¿Ottawa Scale.This work identifies challenges that remain and suggests several key directions for future research.To the best of the authors¿ knowledge, this is the first systematic review to explore this topic.

Background: At present, neonatal resuscitations are documented on the Neonatal Emergence Record, but thorough completion of this record in resuscitations, on average, is poor and less than adequate for proficient, safe and legal documentation. Failure of an accurate representation of a full resuscitation, in real time, can have a bearing on the clinical care given, for example in hypoxic infants. Objectives: The objective is to improve documentation of resuscitation, ensuring accurate, contemporaneous and complete documentation of neonatal resuscitation in real time. Methods: A pilot study evaluated the feasibility, time, cost, adverse events and effect size (statistical variability) to predict an appropriate sample size and improve upon the study design prior to the performance of a full-scale study. Twenty neonatal participants were enrolled in the pilot study. The sequence of randomization was computer generated and blinded to each resuscitation team. Conclusion: The NeRD app achieved higher levels of task completion for majority of the audit criteria. Although only a small study the NeRD app allowed for more accurate and contemporaneous documentation when compared to the current paper-based documentation. In a time where litigation is high and all medical and nursing documentation are scrutinized, high quality, accurate, contemporaneous documentation will be of value. Therefore, the main pilot study is feasible without changes to the protocol. A larger randomized controlled trial is needed for more robust evidence in the use of the NeRD app in documenting neonatal resuscitation.

A preterm birth is a live birth that occurs before 37 completed weeks of pregnancy. Approximately 15 million babies are born preterm annually worldwide, indicating a global preterm birth rate of about 11%. Up to 50% of premature neonates in the gestational age (GA) group of <29 weeks¿ gestation will develop acute kidney injury (AKI) in the neonatal period; this is associated with high mortality and morbidity. There are currently no proven treatments for established AKI, and no effective predictive tool exists. We propose that the development of advanced artificial intelligence algorithms with neural networks can assist clinicians in accurately predicting AKI. Clinicians can use pathology investigations in combination with the non-invasive monitoring of renal tissue oxygenation (rSO2) and renal fractional tissue oxygenation extraction (rFTOE) using near-infrared spectroscopy (NIRS) and the renal resistive index (RRI) to develop an effective prediction algorithm. This algorithm would potentially create a therapeutic window during which the treating clinicians can identify modifiable risk factors and implement the necessary steps to prevent the onset and reduce the duration of AKI.

Background: The aim of the study was to investigate relationship between cord clamping status, total hemoglobin (THb) and total bilirubin (TBil) in term infants requiring phototherapy for neonatal jaundice. Methods: This retrospective study included term infants admitted at the study hospital for management of physiological neonatal jaundice between 2013 and 2019. Associations between THb, TBil, cord clamping status and Direct Coombs Test (DCT) status, as well as correlation between laboratory and blood gas analyzer (BGA) methods were investigated. Results: 258 term infants were included. 147 infants had cord clamping status documented; 111 had unknown cord clamping status. Delayed cord clamping (DCC) was associated with significantly higher mean THb in DCT negative infants only. Negative DCT was associated with higher THb and TBil regardless of cord clamping status. Mean TBil concentration did not change with increasing THb or cord clamping status. The incidence of term infants admitted for phototherapy increased over the study period. There was strong positive correlation between BGA and laboratory assays. Conclusions: DCC was associated with a higher THb in DCT negative infants only. There was no correlation between THb and TBil. There was strong positive correlation of TBil between BGA and laboratory assays thus supporting BGA use in ambulatory care settings.

The effect of smoking and nicotine exposure during pregnancy on fetal nephrogenesis is a growing area of research. The objective of this systematic review is to summarise the current evidence in this research field. Our literature search identified a total of 415 articles from PubMed, Embase, Scopus, and Cochrane. After electronic sorting and manual screening, 18 eligible articles were found, 6 being human studies and 12 being animal studies. Articles that did not study nicotine or smoking, did not focus on fetal kidney development, or did not include nicotine or smoking exposure during pregnancy were excluded from the systematic review. The main outcomes of the studies were kidney weight, volume and size, kidney histopathology and morphology, and kidney function. Evidence from human studies identified a reduction in fetal kidney size, volume, and weight in offspring exposed to smoking during pregnancy; and the greatest impact was seen in offspring exposed to >5-10 cigarettes per day. Animal studies investigated kidney histopathology and highlighted kidney injury and microscopic changes in response to nicotine exposure during pregnancy. Further research is required to determine the impact on kidney function. Recreational nicotine use is evolving, and with the increasing use of urine cotinine in the evaluation of nicotine exposure, further research is needed.

Background: Preterm birth is associated with the development of acute and chronic disease, potentially, through the disruption of normal gut microbiome development. Probiotics may correct for microbial imbalances and mitigate disease risk. Here, we used amplicon sequencing to characterise the gut microbiome of probiotic-treated premature infants. We aimed to identify and understand variation in bacterial gut flora from admission to discharge and in association with clinical variables. Methods: Infants born <32 weeks gestation and <1500 g, and who received probiotic treatment, were recruited in North Queensland Australia. Meconium and faecal samples were collected at admission and discharge. All samples underwent 16S rRNA short amplicon sequencing, and subsequently, a combination of univariate and multivariate analyses. Results: 71 admission and 63 discharge samples were collected. Univariate analyses showed significant changes in the gut flora from admission to discharge. Mixed-effects modelling showed significantly lower alpha diversity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP) and those fed formula. In addition, chorioamnionitis, preeclampsia, sepsis, necrotising enterocolitis and ROP were also all associated with the differential abundance of several taxa. Conclusions: The lower microbial diversity seen in infants with diagnosed disorders or formula-fed, as well as differing abundances of several taxa across multiple variables, highlights the role of the microbiome in the development of health and disease. This study supports the need for promoting healthy microbiome development in preterm neonates. Impact: Low diversity and differing taxonomic abundances in preterm gut microbiota demonstrated in formula-fed infants and those identified with postnatal conditions, as well as differences in taxonomy associated with preeclampsia and chorioamnionitis, reinforcing the association of the microbiome composition changes due to maternal and infant disease.The largest study exploring an association between the preterm infant microbiome and ROP.A novel association between the preterm infant gut microbiome and preeclampsia in a unique cohort of very-premature probiotic-supplemented infants.

Aim: Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital malformation, non-genetic sensorineural hearing loss and neurodevelopmental sequelae in childhood. The primary aim of this retrospective cohort study was to identify the birth and neurodevelopmental outcomes of neonates diagnosed with symptomatic and asymptomatic cCMV in a large regional tertiary referral hospital. Methods: This was a retrospective cohort study of laboratory-based cCMV diagnoses in neonates born at a single study centre between January 2005 and January 2020. Audit of medical records was undertaken to evaluate maternal characteristics, symptom patterns, radiological and neurodevelopmental outcomes of neonates meeting the laboratory diagnostic criteria during the first 24 months. Results: There were 45 neonates with proven CMV infection and 27 mothers with proven infection with an associated pregnancy outcome. Nineteen neonates were born at term (>37 weeks). Of these, 32 (71.1%) neonates had a significant intercurrent comorbidity and 22 (48.9%) neonates were reported to have a degree of delay in one or more developmental domains. A large proportion (77.3%) of the symptomatic untreated neonates had an unknown history of maternal infection compared to the asymptomatic (10.0%) and symptomatic treated (53.8%) neonates (P¿= 0.001). Conclusion: Up to half of the neonates with cCMV were at risk of developing a degree of developmental delay at our centre. Whether these outcomes are related primarily to CMV infection or are confounded by the co-existence of prematurity is unclear and needs further evaluation in prospective studies.

Introduction: The study objectives were to develop standard charts for fetal renal artery blood flow to define normal ranges and to assess the reliability of the measurements. Methods: This prospective, longitudinal study reviewed 72 low-risk singleton pregnancies who had serial ultrasound examinations. Pulse wave Doppler was used to obtain the resistivity and pulsatility indices of the fetal renal arteries. Standard charts of the fetal renal arteries were created using mixed effects modelling and the intra- and interobserver reliability for the renal blood flow measurements was analysed. Results: Standard charts of the normal ranges of the renal artery resistive index (RI) and pulsatility index (PI) of the fetal renal arteries were created. The 3rd, 5th, 10th, 50th, 90th, 95th and 97th centiles were calculated. The intraclass correlation coefficient was acceptable for intraobserver reliability (RI = 0.66, PI = 0.88) and poor for interobserver reliability (RI = 0.11, PI = -0.56). Conclusions: These novel charts demonstrate the change of the fetal renal artery blood flow during pregnancy. These may be used in clinical practice to detect variations from these normal ranges and be useful in future studies of kidney function projection.

Purpose: This project aims to explore healthcare professionals¿ perceptions of providing home phototherapy for neonatal jaundice as part of standard care. Design and Methods: In-depth, semi-structured interviews were conducted with a purposive sample of nine healthcare professionals from the Neonatal Intensive Care Unit. The data was analyzed according to the Interpretive Phenomenological Analysis using six steps devised by Braun and Clarke for thematic analysis using NVivo Software. Results: Six major themes were identified that encompassed healthcare professionals¿ perceptions of home phototherapy for neonatal jaundice. These themes included: baby factors for home phototherapy, better in own environment, parent factors for home phototherapy, perceived benefits for home phototherapy, perceived risks of home phototherapy, and system factors impacting home phototherapy. Conclusions: Home phototherapy was perceived positively amongst the healthcare professionals. The healthcare professionals expressed many perceived benefits of home phototherapy such as family-centred care, improved bonding, improved establishment of breastfeeding, and decreased healthcare expenditure. Practice implications: Enables understanding of the barriers to establishing home phototherapy programs and provides a scaffold for the development of these programs.

Objective: To evaluate the efficacy and safety of home phototherapy for physiological and non-physiological neonatal jaundice compared to in-patient phototherapy. Method: A systematic review of English articles using Medline, CINAHL complete, SCOPUS, and Informit was completed. Additional articles were obtained by a hand-search of the reference lists of obtained articles and Google Scholar. All types of quantitative and qualitative studies were included. Results: 20 articles were identified from our search. Home phototherapy conveyed equal efficacy with inpatient phototherapy with the daily decrement in total serum bilirubin. Home phototherapy was not associated with an increased risk of developing adverse effects. Most of the parents preferred home phototherapy to inpatient phototherapy. Treatment with home phototherapy is more cost effective than inpatient phototherapy. Conclusions: Home phototherapy is a safe and effective treatment for uncomplicated pathological and physiological jaundice. Implications include reduced parental anxiety and decreased healthcare expenditure.

Background: While live streaming from the NICU has entered standard care in some tertiary hospitals, few studies have been explored the impact of this technology upon parents. Aim: To understand the impact of live-streaming vision of infants in NICU to their parents. Method: In the present study, cameras were installed and parents live-streamed vision of their infants while admitted to a regional NICU. Camera usage data were recorded, and parent-infant bonding, parental stress and anxiety data were collected via online survey across four time points. Results: While parents preferred to be with their infant in person, there was strong acceptance of the technology. There were no significant differences in camera usage across the admission and at 3-month follow-up. The relationships between camera usage and bonding, stress, and anxiety scores varied across time points and no significant changes in anxiety, stress and bonding scores were identified. Conclusion: Implementation of this technology into standard care requires streaming stability and support for staff and parents to effectively use the technology.

Preterm infants suffer from a higher incidence of acute diseases such as necrotising enterocolitis and sepsis. This risk can be mitigated through probiotic prophylaxis during admission. This reduction in risk is likely the result of acute modulation of the gut microbiome induced by probiotic species, which has been observed to occur up until discharge. We aimed to determine if this modulation, and the associated probiotic species, persisted beyond discharge. We conducted both a cross-sectional analysis (n = 18), at ~ 18¿months of age, and a longitudinal analysis (n = 6), from admission to 18¿months of the gut microbiome of preterm infants using both shotgun metagenomics and 16S rRNA profiling respectively. The 16S amplicon sequencing revealed that the microbial composition of the probiotic-supplemented infants changed dramatically over time, stabilising at discharge. However, species from the probiotic Infloran®, as well as positive modulatory effects previously associated with supplementation, do not appear to persist beyond discharge and once prophylaxis has stopped. Conclusions: Although differences exist between supplemented and non-supplemented groups, the implications of these differences remain unclear. Additionally, despite a lack of long-term colonisation, the presence of probiotics during early neonatal life may still have modulatory effects on the microbiome assembly and immune system training.What is Known:¿¿Evidence suggests modulation of the microbiome occurs during probiotic prophylaxis, which may support key taxa that exert positive immunological benefits.¿¿Some evidence suggests that this modulation can persist post-prophylaxis.What is New:¿¿We present support for long-term modulation in association with probiotic prophylaxis in a cohort of infants from North Queensland Australia.¿¿We also observed limited persistence of the probiotic species post-discharge.

Aim: To evaluate consistency in the assessment of neonatal skin injuries. Materials and methods: Injury images collected during a multicentre period prevalence study (n = 297) were screened for optimal quality before 60 images, stratified for size and colour, were randomly selected for assessment by three neonatal and two adult specialists. The principal investigator's assessments were the baseline for comparison and consistency. Injury characteristics and assessments were reported as descriptive statistics. Comparison of injury assessments for colour and stage were calculated using Chi-square, with p-value of <0.05 considered significant. Results: Neonatal specialists assessed injury elements more confidently than adult specialists reporting 59¿60 (98¿100%) injuries visible compared to 51¿53 (85¿93%) respectively. Neonatal specialists attributed mechanical force to 93% of the skin injuries compared to 70% by adult specialists. Consistency of colour assessment was achieved more often with neonatal specialists (n = 50, 85%), compared to adult specialists (n = 41, 73%). Neonatal specialists¿ consistency for injury staging (n = 107, 60%) was higher compared to adult specialists who were uncertain (n = 8,16%) and less consistent (n = 47, 44%). When comparing specialists as a group, consistency with baseline assessment was significantly different between neonatal and adult specialists for colour (p < 0.010) and injury stage (p < 0.009). Conclusion: Field of expertise (neonatal versus adult) differences were noted likely related to experience and understanding of empirical differences between neonatal and adult skin structure and maturity. These results highlight the need for specialist neonatal skin injury and wound training for clinicians involved in assessment, treatment and best practices for neonates.

Aim To determine whether being small for gestational age (SGA) is associated with increased mortality and short-term morbidity for extremely low birth weight (ELBW) babies at Townsville University Hospital (TUH). Methods All babies with a birth weight of <1,000 g born at TUH between January 1, 2010 and January 1, 2021 were included. Data from the neonatal unit's NeoDATA database were used to compare mortality and short-term morbidity outcomes for babies categorized as SGA (birth weight <10th centile) or not. Statistical analyses were used to determine associations between being SGA and survival to discharge, intubation for mechanical ventilation, duration of respiratory support, chronic neonatal lung disease (CNLD), home oxygen, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), sepsis, time to full enteral feeds, and duration of admission. Results Of 461 ELBW babies, 62 (13.4%) were SGA. The SGA babies were significantly smaller at 714 (580-850) versus 810 (700-885) g (p < 0.001) and of advanced gestational age at 28.6 (26.6-30.2) versus 25.4 (24.4-26.6) weeks (p < 0.001). No significant difference in mortality existed, with 85% of SGA babies and 84% of others surviving. On univariate analysis, being SGA was associated with significant reductions in intubation for mechanical ventilation (p < 0.001), duration of respiratory support (p < 0.001), intraventricular hemorrhage (p = 0.002), NEC (p = 0.037), and admission duration (p = 0.038). After controlling for confounding factors, no outcomes were independently associated with being SGA. Logistic regression found survival was associated with birth weight (p = 0.030), gestational age (p = 0.007), and antenatal corticosteroids (p = 0.008). Conclusions Being SGA is not an independent predictor of mortality nor adverse short-term morbidity for ELBW babies.

Background: Preterm birth is associated with the development of both acute and chronic disease, and the disruption of normal gut microbiome development. Recent studies have sought to both characterize and understand the links between disease and the microbiome. Probiotic treatment may correct for these microbial imbalances and, in turn, mitigate disease. However, the criteria for probiotic supplementation in NICU's in North Queensland, Australia limits its usage to the most premature (<32 weeks gestation) and small for gestational age infants (<1,500 g). Here we use a combination of amplicon and shotgun metagenomic sequencing to compare the gut microbiome of infants who fulfill the criteria for probiotic-treatment and those who do not. The aims of this study were to determine if probiotic-supplemented preterm infants have significantly different taxonomic and functional profiles when compared to non-supplemented preterm infants at discharge. Methods: Preterm infants were recruited in North Queensland, Australia, with fecal samples collected just prior to discharge (36 ± 0.5 weeks gestation), to capture potential changes that could be probiotic induced. All samples underwent 16S rRNA gene amplicon sequencing, with a subset also used for shotgun metagenomics. Mixed effects models were used to assess the effect of probiotics on alpha diversity, beta diversity and taxonomic abundance, whilst accounting for other known covariates. Results: Mixed effects modeling demonstrated that probiotic treatment had a significant effect on overall community composition (beta diversity), characterized by greater alpha diversity and differing abundances of several taxa, including Bifidobacterium and Lactobacillus, in supplemented infants. Conclusion: Late preterm-infants who go without probiotic-supplementation may be missing out on stabilizing-effects provided through increased alpha diversity and the presence of commensal microbes, via the use of probiotic-treatment. These findings suggest that late-preterm infants may benefit from probiotic supplementation. More research is needed to both understand the consequences of the differences observed and the long-term effects of this probiotic-treatment.

The objective of this study was to explore neonatal skin injury period prevalence, classification, and risk factors. Skin injury period prevalence over 9 months and ¿2, Mann-Whitney U, and independent-samples t tests compared injured and noninjured neonates, with P values less than.05 considered statistically significant. Injury prediction models were developed using Classification and Regression Tree (CART) analysis for the entire cohort and separately for those classified as high or low acuity. The study took place in 3 Australian and New Zealand units. Neonates enrolled (N = 501) had a mean birth gestational age of 33.48 ± 4.61 weeks and weight of 2138.81 ± 998.92 g. Of the 501 enrolled neonates, 206 sustained skin injuries (41.1%), resulting in 391 injuries to the feet (16.4%; n = 64), cheek (12.5%; n = 49), and nose (11.3%; n = 44). Medical devices were directly associated with 61.4% (n = 240) of injuries; of these medical devices, 50.0% (n = 120) were unable to be repositioned and remained in a fixed position for treatment duration. The strongest predictor of skin injury was birth gestation of 30 weeks or less, followed by length of stay of more than 12 days, and birth weight of less than 1255 g. Prediction for injury based on illness acuity identified neonates less than 30 weeks' gestation and length of stay more than 39 days were at a greater risk (high acuity), as well as neonates less than 33 weeks' gestation and length of stay of more than 9 days (low acuity). More than 40% of hospitalized neonates acquired skin injury, of which the majority skin injuries were associated with medical devices required to sustain life. Increased neonatal clinician education and improved skin injury frameworks, informed by neonatal epidemiological data, are vital for the development of effective prevention strategies.

Chronic kidney disease continues to be under recognised and is associated with a significant global health burden and costs. An adverse intrauterine environment may result in a depleted nephron number and an increased risk of chronic kidney disease. Antenatal ultrasound was used to measure the foetal renal parenchymal thickness (RPT), as a novel method to estimate nephron number. Foetal renal artery blood flow was also assessed. This prospective, longitudinal study evaluated the foetal kidneys of 102 appropriately grown and 30 foetal growth-restricted foetuses between 20 and 37 weeks gestational age (GA) to provide vital knowledge on the influences foetal growth restriction has on the developing kidneys. The foetal RPT and renal artery blood flow were measured at least every 4 weeks using ultrasound. The RPT was found to be significantly thinner in growth-restricted foetuses compared to appropriately grown foetuses [likelihood ratio (LR) = 21.06, P = 0.0001] and the difference increases with GA. In foetuses with the same head circumference, a growth-restricted foetus was more likely to have a thinner parenchyma than an appropriately grown foetus (LR = 8.9, P = 0.0028), supporting the principle that growth-restricted foetuses preferentially shunt blood towards the brain. No significant difference was seen in the renal arteries between appropriately grown and growth-restricted foetuses. Measurement of the RPT appears to be a more sensitive measure than current methods. It has the potential to identify infants with a possible reduced nephron endowment allowing for monitoring and interventions to be focused on individuals at a higher risk of developing future hypertension and chronic kidney disease.

Aim: We carried out a longitudinal cohort study to measure serial CysC (Cystatin C) in a cohort of neonates born preterm until the age of 2¿years. We hypothesised that CysC levels are independent of body weight and would not vary with gestational age. Methods: This prospective cohort study was conducted from August 2014 until October 2016, and follow-up was completed in October 2018. Preterm infants at less than 28¿weeks of gestation (extremely preterm infants) were recruited and followed up until the age of 24¿months. Blood samples for measurement of CysC were collected at regular intervals. Results: We recruited 58 preterm neonates with mean gestation was 26.2 (1.5) weeks, and a mean birth weight was 917 (140) g. One-way analysis of variance (ANOVA) did not show any significant difference in CysC levels between 28, 32 and 37¿weeks' gestation (P¿=.09) despite a significant increase in body weight (P¿<.001). The mean CysC level was higher in the neonatal period and subsequently plateaued by 24¿months. Conclusion: Serum CysC level is independent of body weight and not influenced by postnatal age nor by gender.

Background: The stillbirth rate for Australian Aboriginal and Torres Strait Islander infants is twice that for non-Indigenous infants. Autopsy is the gold standard for fetal investigation; however, parental consent is often not given. There is little research investigating the drivers of parents¿ decision-making for autopsy after stillbirth. Aims: The current study explored the reasons why Aboriginal and Torres Strait Islander women did or did not give permission to autopsy after stillbirth. Materials and Methods: Five Aboriginal and/or Torres Strait Islander women participated in semi-structured interviews. Thematic analysis was conducted within a phenomenological framework. Results: Five themes were identified as reasons for giving permission ¿ to find out why the baby died; to confirm diagnosis; to understand future risk; to help others; and doubt about maternal causes. Four themes were identified as reasons for declining permission ¿ not asked in a sensitive manner; not enough time to think; distress about the autopsy procedure; and unwilling to agree. There was a lack of acceptability of the lengthy timeframe for the availability of autopsy results as families usually wait between three and nine months. This lengthy waiting period negatively impacted upon families¿ health and wellbeing. Conclusions: It is important for health professionals to understand the factors that parents consider when giving permission for autopsy after stillbirth. It is hoped that an increase in autopsy rate will enhance the understanding of the causes of stillbirth and ultimately decrease the stillbirth rate for Aboriginal and Torres Strait Islander families.

Background: We carried out a study to determine the impact of prematurity on kidney development in the first 2¿years of life. Methods: In this prospective study, extremely preterm neonates (gestation < 28¿weeks) were recruited and underwent assessments at 6, 12, and 24¿months of age. A cohort of neonates born term were also recruited and followed up for 24¿months. The primary outcomes measured in this study were total kidney volume (TKV) and estimated glomerular filtration rate (eGFR); albuminuria and blood pressure measurements (all provided as mean (standard deviation)) were the secondary outcomes. Results: Fifty-three premature and 31 term neonates (control) were recruited. At the age of 24¿months (corrected age), infants born preterm had significantly smaller TKV (56.1 (9.4) vs. 64.8 (10.2) mL; P = 0.006). There was no difference in eGFR. These preterm infants were smaller (11.25 (1.53) vs. 12.9 (1.8) kg; P = 0.002) and shorter (83.8 (3.0) vs. 86.3 (3.4) cm; P = 0.02) when compared with the control group. At 6, 12, and 18¿months respectively, preterm infants had, relative to their height, significantly smaller kidney volumes (0.54 (0.1) vs. 0.59 (0.1) mL/cm, P = 0.05; 0.61 (0.1) vs.0.71 (0.1) mL/cm, P = 0.003; and 0.67 (0.1) vs.0.76 (0.1) mL/cm, P = 0.006). Conclusions: Relative to body length, TKV in premature infants is smaller. Since length reflects adult body proportions more accurately than BSA, TKV to height ratio may be a more important measure in the child. Despite smaller TKV (and therefore fewer nephrons), infants born prematurely achieve similar eGFRs in the first 24¿months of life, probably due to single-nephron hyperfiltration.

Aim and objective: To explore and establish the language, clinical opinions and workplace culture around neonatal skin injury nomenclature. Specifically, what nomenclature is used to describe, define, identity and communicate neonatal skin injuries including (a) terms, (b) locations, (c) associated risks and (d) mechanical forces. Background: Skin injuries are affirmed or denied based on visual assessment with findings reported by language rather than measurements. However, if language or nomenclature is ambiguous, assessments could be misinterpreted effecting healthcare delivery. Design: Qualitative enquiry including applied discourse analysis and between-method triangulation, within a larger exploratory mixed-methods study. Methods: Data were collected over two years from four sources: literature, documents, interviews/focus groups and free text injury assessments. Data analysis included content analysis, selective coding and thematic analysis. The collective data were further explored using discourse analysis and triangulation to achieve collective conclusions about opinions, emotions, feelings, perceptions and workplace cultures. The COREQ checklist provided structure for the reporting of study methods, analysis and findings. Results: A total of 427 data points were collected from literature, documentation and two clinical data sources. Data convergence revealed that neonatal skin injuries are described by numerous terms with preferences for ¿injury,¿ ¿trauma¿ or ¿redness.¿ Injuries occur in over 20 anatomical locations and risks for injuries included hospitalisation, specific treatments and prematurity. Essential medical devices, clinical condition, lack of clinician experience and overactive neonates were uniquely associated risks. There was incongruency between sources. The literature and documents empathise pressure as the primary force related to skin injury, while varied forces were identified within interviews, focus groups and free text injury assessments. Conclusions: The variety of unique terms, locations and risks for injury indicate the need for updated neonatal skin injury frameworks. If frameworks and policies continue to be created without the empirical knowledge of neonatal clinicians, misrepresentation of neonatal skin injury locations and risk will continue to dominate the literature. Relevance to Clinical Practice: The recognition and management of neonatal skin injuries are related to language used to describe assessments in the absence of diagnostic confirmation, which has implications for both the neonate and the healthcare team.

Aims/hypothesis: Diabetes in pregnancy is thought to adversely affect the developing fetal¿kidneys. The rate of gestational diabetes is increasing globally with major consequences for future renal function. Very little is known about the impact of hyperglycaemia on the fetal renal parenchyma which contains the developing nephrons. The aim of this study was to measure the fetal renal parenchymal thickness and evaluate whether diabetes during pregnancy affects the growth of the fetal kidneys. Methods: This prospective, observational study used serial ultrasound measurements to evaluate the fetal renal parenchymal growth of 55 pregnancies with diabetes compared to 72 control pregnancies. Mixed effects modelling was used to analyse the data. Results: The renal parenchyma of fetuses from mothers with gestational diabetes was significantly thicker than those from the control group (LR Chisq = 4.8, df = 1, p = 0.029), however, the difference was proportional to the larger size of these fetuses. Fetuses of pregestational diabetics demonstrated no significant difference in renal parenchymal thickness compared to the control group even though they were also larger fetuses. Parenchymal growth slowed with increasing abdominal circumference in the pregestational diabetic group, suggesting an adverse effect on nephrogenesis, however this did not reach statistical significance. Conclusions/interpretation: Our study provides unique data on how diabetes during pregnancy influences fetal kidney growth. Appropriate management of diabetic pregnancies may mitigate some of the adverse effects on the fetal kidneys. Increasing degrees of hyperglycaemia, as seen sometimes in pregestational diabetes, may affect nephrogenesis; however larger studies are needed. Graphic abstract: [Figure not available: see fulltext.]

Objective: The objective of this study was to develop new standard growth charts for fetal renal parenchymal thickness, length, and volume to define normal ranges for use in clinical practice and to assess the reliability of these measurements. Methods: This was a prospective, longitudinal study of 72 low-risk singleton pregnancies undergoing serial ultrasound examinations at least every four weeks. Multiple renal measurements were performed on both kidneys at each scan. The renal parenchymal thickness was measured in the mid-sagittal plane. Standard charts were developed and the intra and interobserver reliability for the renal measurements was analysed. Results: Standard charts were developed for fetal renal parenchymal thickness, length, and volume. Conclusion: We present novel charts, which demonstrate the growth of the fetal renal parenchyma during pregnancy. They will be useful in clinical practice to identify any alterations from these normal ranges, which may be an important criterion for assisting prenatal diagnosis of renal pathologies and future studies in the prediction of kidney function.

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.

Background: Advancements in neonatal care have improved survival for premature and very low birth weight (VLBW) infants. Despite this, differences have been reported when comparing males and females. While the previously described concept of the "male disadvantage" asserts that there is a higher risk of mortality and morbidity for male infants, many studies have also found no sex differences in outcomes. Aim: The objective of this study is to determine if the sex of VLBW premature infants is associated with survival and neurodevelopmental outcome in a regional Australian Neonatal Intensive Care Unit (NICU). Methods: A retrospective cohort study was conducted for infants born at < 37 weeks gestation with VLBW (< 1,500 g) admitted to The Townsville Hospital NICU between 2010 and 2015. Comparisons for survival and neurodevelopment between males and females were made with Chi-square, Fisher's exact test and the Independent t-test. Multivariate logistic regression analysis was performed for the outcomes of death before NICU discharge and developmental delay assessed by the Bayley Scales of Infant and Toddler Development, the 3rd Edition. Results: Data were collected for 430 infants. Fifty-three infants died before NICU discharge, with no sex difference in survival. Follow-up assessment was completed for 84 infants from the original cohort and demonstrated no sex differences in neurodevelopmental outcome. Male infants had a significantly higher prevalence of chronic lung disease (p = 0.009). Neither the logistic regression model for death by NICU discharge nor for neurodevelopmental delay identified sex as a significant predictor of outcome. Conclusions: Male and female VLBW premature infants did not differ in survival or neurodevelopmental outcome at this center.

Aim: Indigenous Australians have an increased risk of developing chronic kidney disease (CKD). Indigenous women have a higher rate of CKD than men. In a cohort of Indigenous and non-Indigenous preterm neonates, we assessed total renal volume (TRV) (a proxy indicator for nephron number). We hypothesized that there would be no difference in renal volume between these two groups at term corrected (37 weeks gestation). Methods: Normally grown preterm neonates less than 32 weeks of gestation were recruited and at term corrected dates, the neonates underwent renal ultrasonography (TRV measurements), urine microalbumin-creatinine ratio and serum analysis for Cystatin C measurement for estimated glomerular filtration rate (eGFR) calculation. Results: One hundred and five neonates (38 Indigenous; 67 non-Indigenous) were recruited. Indigenous neonates were significantly more premature and of lower birth weight. At term corrected age, Indigenous neonates had a significantly smaller TRV (18.5 (4.2) vs 21.4 (5.1) cm3; P = 0.027) despite no significant difference in body weight. Despite having a smaller TRV, there was no significant difference in eGFR between Indigenous and Non-indigenous neonates (47.8 [43.2¿50.4] vs 46.2 [42.6¿53.3] ml/min per 1.73 m2; P = 0.986). These infants achieve similar eGFR through hyperfiltration, which likely increases their future risk of CKD. There was no difference in microalbumin-creatinine ratio. Female Indigenous neonates, however, had significantly smaller TRV compared with Indigenous male neonates (15.9 (3.6) vs 20.6 (3.6) cm3; P = 0.006), despite no difference in eGFR, birth weight, gestational age, and weight at term corrected. Conclusion: The difference in TRV is likely to be an important risk factor for the difference in morbidity and mortality from renal disease reported between male and female Indigenous adults.

Purpose: The objective of this study was to investigate the association between prematurity, vascular endothelial growth factor A (VEGF-A), VEGFR-1 (soluble fms-like tyrosine kinase-1 (sFLT-1)) and retinopathy of prematurity (ROP). Methods: A cohort of 53 neonates (gestation <28 weeks) was recruited into this study and peripheral venous samples for VEGF and sFLT-1 measurement were obtained between gestational ages 320¿326 weeks. Results: The mean birth weight for the preterm neonates was 850 (178) g and the median gestational age was 26.4 [24.7¿27.4] weeks. The median VEGF-A level was 1348 [608¿2216] pg/mL and the median sFLT-1 level was 178 [103¿244] pg/mL. Thirty-three neonates (33/53) developed various stages of ROP during their stay in the neonatal unit but only five neonates developed severe (stage 3) ROP needing treatment. The neonates with ROP were smaller (birth weight 801 (111) vs. 990 (175) g; p <.0001), more preterm (gestation 25.4 [24.2¿26.0] vs. 27.1 [26.8¿27.9] weeks; p <.0001) and received supplemental oxygen for a longer duration (1140 [218¿1813] vs. 04 [40¿434] hours; p=.012). There was no statistically significant difference in the VEGF-A level or sFLT-1 levels between those who developed ROP and those who did not. There was a positive correlation between VEGF and both birth weight and gestation, respectively. There was no correlation between sFLT1 and birth weight or gestation. VEGF-A/sFLT-1 ratio in babies treated for ROP was significantly lower compared to those not treated (2.8 [1.0¿5.7] vs. 9.9 [5.6¿13.7]; p =.04). A logistic regression model identified gestational age to be a statistically significant predictor of ROP (odds ratio 0.03 (0.001¿0.550); p =.019). Conclusions: There is no direct correlation between systemic VEGF-A or sFLT-1 plasma levels and severity of ROP in extremely preterm neonates. The link between VEGF and ROP remains to be fully understood.

Dilation and abnormal tortuosity of retinal vessels are the hallmarks of severe retinopathy of prematurity (ROP) in premature infants. The stages of ROP are defined by vessel appearance at the interface between the vascular and avascular retinal areas. Deregulated signaling pathways involving hypoxia-inducible factors such as vascular endothelial growth factor (VEGF) are involved in the pathogenesis of ROP. VEGF-antagonists are increasingly being used as 'off-label medication' to treat this condition, with some success. We present Baby SM (female), who was born prematurely at 24 weeks gestation in a tertiary neonatal intensive care unit, and with a birth weight of 640 g. On screening at 35 weeks postmenstrual age (PMA), she was noted to have ROP, which became severe by 37 weeks PMA. She received one dose of intravitreal VEGF antagonist (Bevacizumab), resulting in a decrease in vessel tortuosity and dilation. However, repeat imaging at 4 weeks showed a re-emergence of vessel tortuosity. We believe the observed changes demonstrate an inherent retinal microvascular plasticity in premature neonates. With improved survival of extremely premature neonates and the availability of retinal imaging technology, we are now able to observe this plasticity.

Purpose To determine the role of ultrasound imaging in evaluating fetal kidney growth. Methods MEDLINE, CINAHL and EMBASE databases were electronically searched for studies between 1996 and January 2017 and limited to English language. Studies were included if they reported on an ultrasound technique to assess fetal kidney growth and they were not a case report or case series. There was independent selection of studies by two reviewers in consensus with one other reviewer. Data were extracted by one reviewer in consensus with two other reviewers. Results A total of 1785 articles were identified. The full text of 39 of these were assessed for eligibility for inclusion. Twenty-eight studies were then included in the review. Standard two dimensional (2D) fetal renal measurements are easy to perform, however, this review identified that most studies had some methodological limitations. The disadvantage with 2D and three dimensional (3D) fetal renal volumes are that they include the entire kidney and good reproducibility of 3D volumes has not yet been demonstrated. Currently there is limited research on fetal kidney growth in the setting of abnormal fetal growth. Research focussing directly on fetal kidney parenchyma and blood flow is scarce. Conclusions Some nomograms of 2D and 3D fetal kidney size and volume have been developed. Kidney length is the most popular single fetal kidney measurement; however, it does not seem to be a good indicator of growth. In IUGR fetuses, kidney length remained similar to appropriately grown fetuses whereas AP and TS dimensions were significantly decreased. New ultrasound techniques focusing on the parenchyma of the kidney and perfusion to the kidney should be explored as they may provide more meaningful information on kidney development in the fetus and future kidney function.

BACKGROUND: Serum creatinine (SCr) measurement to determine glomerular filtration rate (GFR) in neonates has many pitfalls. Cystatin C (CysC) appears to be a more reliable biomarker. METHODS:We investigated the effect of birth weight on SCr and CysC measurements in a cohort of 74 infants, consisting of both term and ex-premature infants at term postmenstrual age. SCr and Cys C measurements were carried out at the same time. RESULTS: Eighty six infants were recruited into this study out of which complete data were available in 80 infants. The cohort consists of both term and premature infants at term PMA (31 terms and 49 preterms). The median SCr level was 17 [12-26] umol/L and mean CysC level was 1.64 [0.27] mg/L. SCr had a significant correlation with weight (r = 0.3; P = 0.011), whereas serum CysC had no correlation with the infant's weight (r = 0.01; P = 0.95). There were no statistically significant difference in SCr and CysC between male and female infants. CONCLUSION: Unlike CysC, SCr had a significant correlation with birth weight. SCr based GFR measurement may cause a delay in diagnosis of acute kidney injury in smaller neonates.

Vascular endothelial growth factor-A (VEGF-A) plays an integral role in physiological and pathophysiological angiogenesis and has increasingly been implicated in the development of retinopathy of prematurity (ROP) in preterm infants. Application of intravitreal anti-VEGF is frequently used to treat ROP with little consideration given to the role of VEGF-A in neonatal growth and development. Previous studies have demonstrated systemic anti-VEGF persistence, reduced peripheral VEGF levels following treatment, and possible diagnostic and prognostic uses for VEGF-A determination. This study seeks to determine a normal range for serum VEGF-A (sVEGF-A) in healthy, term infants. The sVEGF-A levels were obtained from 32 neonates born at term infants (16 males and 16 females) using an enzyme-linked immunosorbent assay. No significant correlations were found between sVEGF-A levels and time of sample collection, birth weight, or gender. The median sVEGF-A level was 976 (394-1635) pg/mL (95% confidence interval for median: 496-1,318 pg/mL). This preliminary study determines a normal range for the sVEGF-A level in healthy, term neonates. This normal range will provide a tool to assist in the diagnosis, prognosis, and monitoring of treatment of infants with ROP.

Studies have highlighted that antenatal steroids could have an effect on neonatal skin maturation. This study examined if there was a relationship between the administration of antenatal glucocorticoids for mothers and the skin injuries in their neonates. Data from skin injury audit were extracted from the neonatal database and analyzed to determine differences in the prevalence of neonates with pressure injuries [cases] whose mothers had received antenatal steroids, compared to those without pressure injuries [control]. RESULTS: Of 247 neonates audited, 77 [31%], had documented pressure injuries, 170 [69%] had no documented injury. The median birth weight and gestation were 1400 g [IQR 893-2268 g] and 30.3 weeks [IQR 26.3-40.0 weeks] respectively. Of the neonates born less than 34 weeks, 80% were exposed to antenatal steroids and were equally distributed across patient genders. Within the 77 cases, 53 [66%] were exposed to antenatal steroids compared to controls in which 88 [53%] had not. The effect between cases and controls was not statistically significant [¿2 =2.81, P =0.09]. However a difference was noted between genders, as female neonates benefited from the exposure to steroids [OR =0.317, 95% [CI 0.105-0.956], p value-0.041]. CONCLUSION: Antenatal glucocorticoids appear to be beneficial in reducing pressure injury prevalence in female neonates.

Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency, present at birth. It is seen in 1:4,000 births and is caused by an anatomical defect, known as thyroid dysgenesis (underdevelopment or unusual location of the thyroid gland), by abnormal biosynthesis of the thyroid hormones (dyshormogenesis), inborn errors of metabolism, genetic mutations or iodine deficiency. If untreated, severe neurological impairment develops. However, newborn screening programs have improved outcomes greatly, through early diagnosis and treatment. Clinical manifestations are often subtle at birth, due to the placental transfer of thyroxine (T4), thus making diagnosis in the first few days of life difficult. Increased levels of thyroid stimulating hormone (TSH) and low levels of T4 are confirmatory for this disorder. We describe the case of a baby with CH who presented with neonatal seizures: a rare clinical presentation. Our case highlights the need to eliminate CH, as a cause of seizures, so that treatment can be initiated even more promptly to optimize neurological sequelae and outcome.

© 2015 Taylor & Francis Group, LLC Objectives: Nephrin is an integral part of podocytes that together with endothelial cells and the basement form the glomerular filtration barrier. Placental ischemia triggers a cascade of events that ultimately result in endothelial malfunction, hypertension, podocytopathy and fetal compromise. Methods: We review the literature to determine if urine nephrin measurements could serve as a useful biomarker to detect early podocyte injury in pre-eclampsia. Results: Our search identifies eight studies published to date. The findings of these studies demonstrate that urine nephrin excretion plays a critical role in the pathogenesis of proteinuria during pre-eclampsia and that this is a good indicator of glomerular injury. Conclusion: There is thus an urgent need for a large multi-centre clinical study using standardized recruitment criteria to determine the full potential of this biomarker in clinical practice.

Northern Queensland is unique in that the proportion of Aboriginal and Torres Straits Islander (ATSI) communities is higher than the rest of Australia. The aim of this study was to describe the characteristics of term admissions of low birth weight (LBW; birth weight < 2,500¿g) and small for gestational age (SGA; birth weight < 10th centile) infants to a neonatal unit. All term infants (>37¿weeks of gestation) with LBW and/or SGA admitted to the neonatal unit over the last 10¿years (2002¿2011) were identified and the percentage calculated. Ethnicity was determined by the mother and that information was recorded in the patient¿s medical record. The average percentage of LBW ATSI infants was 20.2¿±¿5.7¿%, which was significantly higher (almost double) compared with the percentage of LBW non-ATSI infants (10.2¿±¿1.9¿%; p¿<¿0.001). The average percentage of SGA ATSI infants was also significantly higher than the percentage of SGA non-ATSI infants (31.8¿±¿6.0 vs. 18.6¿±¿2.8¿%, respectively; p¿<¿0.001). The mean percentage of LBW indigenous infants admitted to the neonatal unit was significantly higher than non-ATSI infants.

Background Group B Streptococcus (GBS) infection is recognised as an important cause for neonatal sepsis. Aims To describe the incidence and risk factors for invasive GBS under 90 days of age in North Queensland from January 2002 to December 2011. Material and Methods Patients were identified with positive blood and cerebrospinal fluid cultures to obtain incidence figures. The Townsville district cohort was further investigated for the presence of maternal and fetal risk factors in a retrospective case-controlled study. Results Early onset GBS continues to occur at 0.43/1000 live births, and late onset disease at 0.38/1000 live births. Early onset GBS and late onset GBS are shown to be two distinct diseases. Early onset disease is significantly different from the control group for these risk factors: previous late fetal loss, prolonged rupture of membranes, inadequate intrapartum antibiotics, abnormal cardiotocography, delivery by emergency caesarean section, lower one minute Apgar scores and need for resuscitation at delivery. Significant variables for late onset disease are earlier gestation and need for resuscitation at birth, first born babies, multiple pregnancy and birth by emergency caesarean section. The incidence of early or late onset GBS in Aboriginal or Torres Strait Islanders was not significantly different. Conclusions Group B Streptococcus continues to occur in North Queensland at higher than expected rates, and a new approach to its prevention should be considered. Previous fetal loss may be a risk factor which is under recognised. Babies with late onset infection appear to be significantly more preterm. © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Aim: Pressure related skin injuries (including ulceration, skin/epithelial stripping, and combination injuries) have historically been neglected within neonatal research. Although anecdotal evidence, wound reviews and isolated case studies have been published; there is limited research specific to neonatal pressure injuries despite this population being, arguably, the most vulnerable patient group.The objective of this study was to investigate specific rates of neonatal skin breakdown from pressure including locations, stages, and etiology associated with tissue damage. Methods: A descriptive cohort study was conducted in North Queensland's Tertiary perinatal center over a 2-year period. Prevalence audits for pressure injuries to the skin were conducted (including epithelial stripping) and incorporated categorization of with degree of tissue breakdown between Stage 1-4. A modified risk assessment and prevalence tool was utilized in this study. Results: 247 neonatal patients were reviewed during the study period, of these infants, 77/247 were identified as having a skin injury (a prevalence rate of 31.2%). In total, 107 injuries were identified with the mean number of 1.4 injuries (range 1-4, SD 0.71). The mean gestational age was 28 weeks (range 22-41 weeks, SD 4.1 weeks) and the mean birth weight was 1155g (range 445-2678g, SD 620g). Factors identified as contributing to pressure injuries included indwelling vascular catheters (22.4%), non-invasive continuous positive airway pressure delivery devices (14.0%), oxygen saturation and temperature probes (17.8.%). 31.8% of injuries could not be associated with a specific risk factor. Conclusions: Neonates are undeniably at risk for pressure injuries however; it is still unclear which proportions of injuries are entirely preventable. Further development of a risk assessment and prevalence tool will provide practitioners with insight into the specific risk factors applicable for neonatal pressure injuries. Additional studies with larger patient groups will more accurately update practice related to pressure injury prevention and management in neonatal units; as well as critically evaluate the adverse affects of routine care processes that unintentionally harm the skin of these fragile patients. © 2013 Neonatal Nurses Association.

Low birth weight (LBW, <2500g) infants have a reduced number of glomeruli and nephrons and, therefore, smaller kidneys. The purpose of this pilot study was to determine whether renal parenchymal thickness might be a better indicator of renal growth. We carried out a pilot study over 12mo to determine whether renal parenchymal thickness could be used to detect differences in renal growth between LBW and normal birth weight (NBW, 2500-4500g) infants. Thirty-eight term infants (12 LBW and 26 NBW) underwent renal ultrasound. Parenchymal thickness, length, transverse diameter and antero-posterior diameter were measured. Mean renal parenchymal thickness was significantly lower in LBW infants than in NBW infants. Renal parenchymal thickness wasclosely correlated with an increase in renal volume (r=0.76, p<0.0001). Renal parenchymal thickness is a single measurement that could potentially be a more useful and accurate approach to monitoring renal growth in growth-restricted infants than renal volume. © 2013.