‘Joining the Dots: Linking Prenatal Drug Exposure to Childhood and Adolescence’ – Research Protocol of a Population Cohort Study

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal social demographics or social determinants of health, and maternal physical and mental health comorbidities. Key outcome measures will include child mortality, academic standardised testing results, rehospitalisation and maternal survival. Data analysis will be conducted using Stata V.18.0. ETHICS AND DISSEMINATION: Approvals were obtained from the NSW Population and Health Services Research Ethics Committee (29 June 2020; 2019/ETH12716) and the Australian Capital Territory Health Human Research Ethics Committee (11 October 2021; 2021-1231, 2021-1232, 2021-1233); and the Aboriginal Health and Medical Research Council (5 July 2022; 1824/21), and all Australian educational sectors: Board of Studies (government schools), Australian Independent Schools and Catholic Education Commission (D2014/120797). Data were released to researchers in September 2022. Results will be presented in peer-reviewed academic journals and at international conferences. Collaborative efforts from similar datasets in other countries are welcome

‘Joining the Dots: Linking Prenatal Drug Exposure to Childhood and Adolescence’ – Research Protocol of a Population Cohort Study

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal social demographics or social determinants of health, and maternal physical and mental health comorbidities. Key outcome measures will include child mortality, academic standardised testing results, rehospitalisation and maternal survival. Data analysis will be conducted using Stata V.18.0. ETHICS AND DISSEMINATION: Approvals were obtained from the NSW Population and Health Services Research Ethics Committee (29 June 2020; 2019/ETH12716) and the Australian Capital Territory Health Human Research Ethics Committee (11 October 2021; 2021-1231, 2021-1232, 2021-1233); and the Aboriginal Health and Medical Research Council (5 July 2022; 1824/21), and all Australian educational sectors: Board of Studies (government schools), Australian Independent Schools and Catholic Education Commission (D2014/120797). Data were released to researchers in September 2022. Results will be presented in peer-reviewed academic journals and at international conferences. Collaborative efforts from similar datasets in other countries are welcome

Neonatal abstinence syndrome and high school performance

BACKGROUND AND OBJECTIVES: Little is known of the long-term, including school, outcomes of children diagnosed with Neonatal abstinence syndrome (NAS) (International Statistical Classification of Disease and Related Problems [10th Edition], Australian Modification, P96.1). METHODS: Linked analysis of health and curriculum-based test data for all children born in the state of New South Wales (NSW), Australia, between 2000 and 2006. Children with NAS (n = 2234) were compared with a control group matched for gestation, socioeconomic status, and gender (n = 4330, control) and with other NSW children (n = 598 265, population) for results on the National Assessment Program: Literacy and Numeracy, in grades 3, 5, and 7. RESULTS: Mean test scores (range 0-1000) for children with NAS were significantly lower in grade 3 (359 vs control: 410 vs population: 421). The deficit was progressive. By grade 7, children with NAS scored lower than other children in grade 5. The risk of not meeting minimum standards was independently associated with NAS (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 2.2-2.7), indigenous status (aOR, 2.2; 95% CI, 2.2-2.3), male gender (aOR, 1.3; 95% CI, 1.3-1.4), and low parental education (aOR, 1.5; 95% CI, 1.1- 1.6), with all Ps < .001. CONCLUSIONS: A neonatal diagnostic code of NAS is strongly associated with poor and deteriorating school performance. Parental education may decrease the risk of failure. Children with NAS and their families must be identified early and provided with support to minimize the consequences of poor educational outcomes

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Neonatal Abstinence Syndrome: Prevention, Management and Outcomes: From Birth to Adulthood

Neonatal abstinence syndrome (NAS), or&mdash;when specifically focused on opioids&mdash;neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome in neonates after birth causally related to the in utero exposure to drugs of dependence, and the subsequent acute interruption at delivery [...

Inflammatory imbalance in the development of bronchopulmonary dysplasia.

AbstractIntroduction: Current evidence suggests that the lungs of infants with the debilitating disorder, bronchopulmonary dysplasia (BPD), react to the challenges of extra-uterine adaptation with inappropriately aggressive inflammation. The reasons for this are not entirely clear and this study hypothesizes that a deficiency of interleukin (IL)-10, a potent anti-inflammatory mediator, leads to the functional and architectural changes characteristic of BPD. Aim: To characterize the behaviour of IL-10 and neutrophil apoptosis in the tracheal fluids (TF) of infants at risk of developing BPD.Method: TF from intubated infants of varying gestations at the Royal Hospital for Women, Randwick was spun and ILs 8, 10 and 16 were measured in the supernatant. The residual pellets of white cells were used to determine differential white cell counts and neutrophil apoptosis.Results: None of the 20 TF specimens from the extremely premature infants with BPD (n=11) had detectable IL-10, compared to 14/20(70%) of the specimens from preterm infants without BPD (n=20) and to 5/19 (26%) of the specimens from term infants (n=19). BPD infants also had a significantly lower number of apoptotic neutrophils during the 1st week of life. Premature infants with TF IL-10 &gt5pg/ml did not develop BPD. Levels of IL-8, a neutrophil chemotaxin, and white cell counts, while not differing significantly between the groups, increased considerably towards the end of the first week of life in the BPD group. IL-16, a chemotaxin for inflammatory CD4+ cells, was also detected in more BPD than non-BPD specimens (BPD: 16/46 (35%) v 1/30 (0.3%) non-BPD preterm and 2/7 (28%) term TF specimens).Conclusions: Extremely premature infants prone to BPD have decreased pulmonary anti-inflammatory activity as demonstrated by decreased IL-10 and apoptotic neutrophils in tracheal fluids. The lack of a counter-regulatory response to the inflammatory processes that are an inevitable consequence of extra-uterine adaptation may therefore place the extremely premature newborn infant at a considerable risk of developing BPD

Profile of infants born to drug-using mothers: A state-wide audit

Aim:s: To ascertain the characteristics and short-term outcomes of infants born to illicit drug-using mothers in public hospitals in the state of New South Wales and the Australian Capital Territory during 2004. Methods: Patients were identified retrospectively by hospital records searches using ICD-10 morbidity codes and records of local Drug and Alcohol Services. Records were reviewed on site. All public hospitals (n= 101) with obstetric services were included. Results: A total of 879 (1.4%, 95% confidence interval: 1.3-1.5%) drug-using mothers were identified from 62 682 confinements. Opiates (46.8%), amphetamines (23.0%) and polydrug (16.4%) exposure were most common. There were eight stillbirths. Among these 871 infants, prematurity (23.6%) and low birthweight (27.1%) were common and 51.1% were admitted to nurseries for further care. Two infants died. Major congenital anomalies were detected in 15 infants. Pharmacological treatment for withdrawal was required for 202 (23.2%), and 143 (70.8%) infants were discharged home on medication. Infants who completed inpatient pharmacological treatment were hospitalised longer (median 26.0 vs. 12.0 days) and were more likely to be premature (37.3 vs. 14.0%). Child-at-risk notifications affected 40.6% of the infants, and 7.6% were fostered prior to discharge. A total of 333 (38.2%) infants were breastfed at discharge. Conclusions: Our regional study highlights a substantial prevalence of drug use in pregnancy with considerable adverse perinatal and hospital outcomes in infants born to these mothers. Coordinated health care and resources are needed to support these mother-infant pairs because of their social, medical and mental-health issues

Oxygen therapy of the newborn from molecular understanding to clinical practice

Oxygen is one of the most critical components of life. Nature has taken billions of years to develop optimal atmospheric oxygen concentrations for human life, evolving from very low, peaking at 30% before reaching 20.95%. There is now increased understanding of the potential toxicity of both too much and too little oxygen, especially for preterm and asphyxiated infants and of the potential and lifelong impact of oxygen exposure, even for a few minutes after birth. In this review, we discuss the contribution of knowledge gleaned from basic science studies and their implication in the care and outcomes of the human infant within the first few minutes of life and afterwards. We emphasize current knowledge gaps and research that is needed to answer a problem that has taken Nature a considerably longer time to resolve

Population study of neurodevelopmental outcomes of extremely premature infants admitted after office hours

Aim The aim of the study was to compare neurodevelopmental outcomes of extremely preterm infants admitted during (OH) and after (AH) office hours. Methods A retrospective review of the New South Wales and Australian Capital Territory Neonatal Intensive Care Units' (NICUs) Data Collection of all infants 2 standard deviations below the mean), cerebral palsy (unable to walk without aids), deafness (requiring bilateral hearing aids) or blindness (visual acuity <6/60 in the better eye). Results Mortality and age at follow-up were comparable between the AH and OH groups. Developmental outcome was evaluated in 972 (74.9%) infants admitted during AH and 501 (74.6%) admitted during OH. FD was not significantly different between the AH and OH groups (17.1% vs. 14.8%, adjusted odds ratio 1.131, 95% confidence interval 1.131 (0.839-1.523), P = 0.420). There were no significant differences between AH and OH infants with cerebral palsy (9.6% vs. 7.6%), developmental delay (5.4% vs. 5.0%) or any other component of FD. Conclusion There is little circadian variation in mortality and adverse neurodevelopmental outcomes in an NICU network with the current model of after hours staffing and support, and sharing of NICU workload within a network