Perinatal mortality among term births: Informing decisions about singleton early term births in Western Australia.

Background: To minimise the risk of perinatal mortality, clinicians and expectant mothers must understand the risks and benefits associated with continuing the pregnancy.

Objectives: Report the gestation-specific risk of perinatal mortality at term.

Methods: Population-based cohort study using linked health data to identify all singleton births at gestations 37-41 weeks, in Western Australia (WA) from 2009 to 2019.

Routine transabdominal cervical length screening in mid-pregnancy for the prevention of preterm birth: Is it good enough to use as a screening test?

Background: Preterm birth (PTB) is a major pregnancy complication. There is evidence that a short cervical length in mid-pregnancy may predict women at increased risk of PTB.

Aims: To evaluate the utility of population-based, transabdominal cervical length (TACL) measurement screening in mid-pregnancy for PTB prediction in women.

Ascertainment of Aboriginal and Torres Strait Islander status for assessment of perinatal health outcomes: Reported versus derived maternal ethnicity in Western Australian pregnancy data.

Background: Under-identification of Aboriginal and Torres Strait Islander (hereafter referred to as Aboriginal) people can result in inaccurate estimation of health outcomes. Data linkage has improved identification of Aboriginal people in administrative datasets.

Aim: To compare three methods of ascertainment of Aboriginal status using only pregnancy data from the Western Australian Midwives Notification System (MNS), to the linked Indigenous Status Flag (ISF) derived by the Department of Health.

The Relationship Between Early Term Birth and the Risk of Later Childhood Mental Disorders Within a Pregnancy Cohort.

This study examines whether gestational age, birth weight, and early term birth is associated with childhood mental disorders in 342 pregnant women recruited at less than 20 weeks gestation and were then followed up until 4 years postpartum, including 93 children born at early term. Women were assessed at recruitment using the Structured Clinical Interview for DSM. At 4 years of age their children were assessed using the Preschool Age Psychiatric Assessment (PAPA) and the Child Behavior Checklist (CBCL).

Respiratory benefit in preterm lambs is progressively lost when the concentration of fetal plasma betamethasone is titrated below two nanograms per milliliter.

Antenatal steroid therapy is the standard of care for women at imminent risk of preterm delivery. Current dosing regimens use suprapharmacological doses to achieve extended fetal steroid exposures. We aimed to determine the lowest fetal plasma betamethasone concentration sufficient to achieve functional preterm lung maturation.

Characterisation of Mid-Gestation Amniotic Fluid Cytokine and Bacterial DNA Profiles in Relation to Pregnancy Outcome in a Small Australian Cohort.

A well-established association exists between intrauterine bacteria and preterm birth. This study aimed to explore this further through documenting bacterial and cytokine profiles in Australian mid-gestation amniotic fluid samples from preterm and term births. Samples were collected during amniocenteses.

Effects of multiple pro-inflammatory stimuli on the ileum of extremely premature ovine fetuses.

Introduction: Chorioamnionitis is common in preterm birth and associated with a higher risk of intestinal inflammation and necrotizing enterocolitis. The intestinal inflammation influences the enteric nervous system development. We hypothesized that inflammation and innervation in the fetal ileum may be modified by chorioamnionitis induced by repeated challenge with lipopolysaccharide and/or preexisting infection at very low gestational age equivalent to 60% of term.

A Reduction in Antenatal Steroid Dose Was Associated with Reduced Cardiac Dysfunction in a Sheep Model of Pregnancy.

Despite widespread use, dosing regimens for antenatal corticosteroid (ACS) therapy are poorly unoptimized. ACS therapy exerts a programming effect on fetal development, which may be associated with an increased risk of cardiovascular disease. Having demonstrated that low-dose steroid therapy is an efficacious means of maturing the preterm lung, we hypothesized that a low-dose steroid exposure would exert fewer adverse functional and transcriptional changes on the fetal heart.

Fetal Growth Trajectories and Measures of Insulin Resistance in Young Adults.

Context: Events during gestation greatly influence the risk of cardiometabolic diseases including diabetes in offspring during later life.

Objective: This study aimed to investigate relationships between serial ultrasound-derived fetal growth trajectories and markers of insulin resistance in young adults in the Raine Study, an Australian pregnancy cohort.

Methods: Linear mixed modeling examined the relationship between fetal growth trajectory groups, constructed using serial ultrasound-based abdominal circumference (AC), femur length (FL), and head circumference (HC) from 1333 mother-fetal pairs, and offspring Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), as a marker of diabetes risk, at 20 (n = 414), 22 (n = 385), and 27 (n = 431) years.

Associations between Prenatal Exposure to Phthalates and Features of the Metabolic Syndrome in Males from Childhood into Adulthood.

Phthalate metabolites are detectable within the majority of the population. Evidence suggests that a prenatal exposure to phthalates may be associated with the subsequent risks of obesity and elevated blood pressure. We hypothesised that a prenatal exposure to phthalates would lead to an increase in adverse cardiometabolic parameters through childhood and adulthood.

Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model.

Treatment with antenatal steroids (ANS) is standard practice for reducing the risk of respiratory distress in the preterm infant. Despite clear overall benefits when appropriately administered, many fetuses fail to derive benefit from ANS therapies. In standardized experiments using a pregnant sheep model, we have demonstrated that around 40% of ANS-exposed lambs did not have functional lung maturation significantly different from that of saline-treated controls.

Relationships between intrauterine fetal growth trajectories and markers of adiposity and inflammation in young adults.

Background: There is now good evidence that events during gestation significantly influence the developmental well-being of an individual in later life. This study aimed to investigate the relationships between intrauterine growth trajectories determined by serial ultrasound and subsequent markers of adiposity and inflammation in the 27-year-old adult offspring from the Raine Study, an Australian longitudinal pregnancy cohort.

Methods: Ultrasound fetal biometric measurements including abdominal circumference (AC), femur length (FL), and head circumference (HC) from 1333 mother-fetal pairs (Gen1-Gen2) in the Raine Study were used to develop fetal growth trajectories using group-based trajectory modeling.

The complex challenge of antenatal steroid therapy nonresponsiveness.

Antenatal steroid therapy is standard care for women at imminent risk of preterm delivery. When deliveries occur within 7 days of treatment, antenatal steroid therapy reduces the risk of neonatal death and improves preterm outcomes by exerting diverse developmental effects on the fetal organs, in particular the preterm lung and cardiovascular system. There is, however, sizable variability in antenatal steroid treatment efficacy, and an important percentage of fetuses exposed to antenatal steroid therapy do not respond sufficiently to derive benefit.

The clinical utility of ongoing sonographic cervix length surveillance in pregnancies prescribed vaginal progesterone therapy.

Background: Vaginal progesterone therapy significantly reduces preterm birth (PTB) rates in those high-risk pregnancies with a sonographic short cervix (≤25 mm) and/or a history of spontaneous PTB. Cervical length (CL) is routinely measured at the midtrimester morphology scan; however, CL surveillance thereafter is not currently recommended. Progesterone's precise mechanism of action remains unknown, though if it indeed influences CL, shortening after treatment initiation could indicate therapeutic failure and risk of PTB.

The Relationship Between Fetal Growth and Retinal Nerve Fiber Layer Thickness in a Cohort of Young Adults.

Purpose: To explore relationships between patterns of fetal anthropometric growth, as reflective of fetal wellbeing, and global retinal nerve fiber layer (RNFL) thickness measured in young adulthood.

Methods: Participants (n = 481) from within a Western Australian pregnancy cohort study underwent five serial ultrasound scans during gestation, with fetal biometry measured at each scan. Optic disc parameters were measured via spectral-domain optical coherence tomography imaging at a 20-year follow-up eye examination.

Low-dose antenatal betamethasone treatment achieves preterm lung maturation equivalent to that of the World Health Organization dexamethasone regimen but with reduced endocrine disruption in a sheep model of pregnancy.

Background: The intramuscular administration of antenatal steroids to women at risk of preterm delivery achieves high maternal and fetal plasma steroid concentrations, which are associated with adverse effects and may reduce treatment efficacy. We have demonstrated that antenatal steroid efficacy is independent of peak maternofetal steroid levels once exposure is maintained above a low threshold.

Objective: This study aimed to test, using a sheep model of pregnancy, whether the low-dose antenatal steroid regimen proposed as part of the Antenatal Corticosteroids for Improving Outcomes in Preterm Newborns trial would achieve preterm lung maturation equivalent to that of the existing World Health Organization dexamethasone treatment regimen, but with reduced risk of adverse outcomes.

Perinatal care for the extremely preterm infant.

Being born preterm (prior to 37 weeks of completed gestation) is a leading cause of childhood death up to five years of age, and is responsible for the demise of around one million preterm infants each year. Rates of prematurity, which range from approximately 5 to 18% of births, are increasing in most countries. Babies born extremely preterm (less than 28 weeks' gestation) and in particular, in the periviable (20-25 weeks) period, are at the highest risk of death, or the development of long-term disabilities.

One percent of the clinical dose used for antenatal steroid therapy is sufficient to induce lung maturation when administered directly to the preterm ovine fetus.

Antenatal steroids (ANSs) are routinely administered to women judged to be at imminent risk of preterm delivery. Their principal benefit is precocious functional maturation of the preterm fetal lung. Current dosing regimens expose the mother and fetus to high steroid levels that may be unnecessary, increasing the potential risks of disruption to the maternal and fetal hypothalamic-pituitary-adrenal (HPA) axis and glucose regulation, alterations in placental function, and reduced fetal growth.

Continuous but not pulsed low-dose fetal betamethasone exposures extend the durability of antenatal steroid therapy.

Antenatal steroid (ANS) therapy is the standard care for women at imminent risk of preterm labor. Despite extensive and long-standing use, 40%-50% of babies exposed antenatally to steroids do not derive benefit; remaining undelivered 7 days or more after ANS treatment is associated with a lack of treatment benefit and increased risk of harm. We used a pregnant sheep model to evaluate the impact of continuous versus pulsed ANS treatments on fetal lung maturation at an extended, 8-day treatment to delivery interval.

Prenatal tobacco and alcohol exposures and the risk of anxiety symptoms in young adulthood: A population-based cohort study.

Background: Epidemiological studies have linked prenatal tobacco and alcohol exposures to internalizing behaviours in children and adolescents with inconsistent findings. Dearth of epidemiological studies have investigated the associations with the risk of experiencing symptoms of anxiety in young adulthood.

Methods: Study participants (N = 1190) were from the Raine Study, a population-based prospective birth cohort based in Perth, Western Australia.

Prenatal alcohol exposure and offspring subsequent alcohol use: A systematic review.

Background: Prenatal alcohol exposure has been found to be associated with adverse physical and mental health outcomes in postnatal life, but the evidence is equivocal as to whether such exposure increases the risk of subsequent alcohol use in the offspring. We systematically reviewed the literature on the association between prenatal alcohol exposure and subsequent alcohol use in the offspring.

Methods: Relevant primary studies were identified via systematic search of PubMed/Medline, SCOPUS, EMBASE and Psych-INFO databases.

Prenatal alcohol and tobacco exposures and the risk of cannabis use in offspring: Findings from a population-based cohort study.

Background: There is a paucity of prospective longitudinal studies examining the associations between maternal use of alcohol and tobacco during pregnancy and the risk of cannabis use in offspring. The aim of this study was to examine the association between prenatal alcohol and tobacco exposures and offspring cannabis use.

Methods: Data were from the Raine Study, a longitudinal prospective birth cohort based in Western Australia.

Assessment of synthetic red cell therapy for extremely preterm ovine fetuses maintained on an artificial placenta life-support platform.

Background: Artificial placenta therapy (APT) is an experimental care strategy for extremely preterm infants born at 21-24 weeks' gestation. In our previous studies, blood taken from the maternal ewe was used as the basis of priming solutions for the artificial placenta circuit. However, the use of maternal blood as a priming solution is accompanied by several challenges.

Missing out on precious time: Extending paid parental leave for parents of babies admitted to neonatal intensive or special care units for prolonged periods.

In Australia, approximately 18% of newborn babies are admitted to a neonatal intensive or special care nursery. While most babies admitted to a neonatal intensive or special care nursery are discharged home within a few weeks, around 6% of babies spend more than 2 weeks in hospital. For the parents of these babies, much of their leave entitlements (Australian Government Paid Parental Leave Scheme is up to18 weeks for the primary care giver and up to 2 weeks for partners) are used before their baby comes home from hospital.