To assess the impact of gestational diabetes(GDM) detection thresholds on infant growth, nutrition, and neurodevelopment at 12-18 months. Prospective cohort study within the GEMS trial(ACTRN12615000290594), which randomized pregnant women to detection of GDM using lower or higher glycemic criteria. The main outcomes were overweight/rapid weight gain; food approach appetitive score; energy intake; cognitive z-score. Compared to control infants, those exposed to GDM detected and treated by higher criteria or by lower but not higher criteria that was untreated, were less likely to have increased overweight/rapid weight gain, possibly with lower energy intake. There were no important differences in appetite and cognition. Infants exposed to GDM by lower but not higher criteria that was treated were similar to controls. Exposure to treated GDM or untreated GDM detected by lower but not higher criteria, was not associated with increased infant risk factors for obesity or adverse cognitive outcomes.

Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero ( F 1 ) and in the second generation ( F 2 ). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation ( F 2 ) of Auckland Steroid Trial (AST) participants. In the AST, women ( F 0 ) expected to birth between 24 and 36 weeks’ gestation were randomised to betamethasone or placebo. When their children ( F 1 ) were 50 years old, they and their children ( F 2 ) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the F 2 generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 F 2 participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean ( SD ) 0.63 (1.45), N = 77 vs 0.41 (1.28), N = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.

BACKGROUND:For women who have received a course of antenatal corticosteroids ≥7 days prior and have ongoing risk of preterm birth within the next 7 days, repeat dose(s) of corticosteroids up to 32 weeks' gestation have been shown to reduce neonatal respiratory distress syndrome and serious health problems in the neonatal period but not other neonatal morbidities such as chronic lung disease, death, severe intraventricular haemorrhage or necrotising enterocolitis. Repeat antenatal corticosteroids were not associated with either benefit or harms in mid-childhood. However, this may have been too early to evaluate potential adverse effects on respiratory and other long-term outcomes. We aimed to assess if exposure to repeat dose(s) of antenatal corticosteroids administered to pregnant women up to 32 weeks' gestation has beneficial or harmful effects on respiratory and general health of the offspring in adulthood. METHODS AND FINDINGS:We assessed the adult offspring of New Zealand participants in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids for the Prevention of Neonatal Respiratory Disease (ACTORDS), a multicentre, placebo-controlled trial where women at risk of preterm birth within the next week, 7 or more days after having received a single course of corticosteroids were randomised to a repeat dose of intramuscular betamethasone or placebo, that could be repeated weekly if at ongoing preterm birth risk. Follow-up at 20 years included a health questionnaire and consent to access administrative data sources. The primary outcome was any asthma diagnosis. Secondary outcomes included neurodevelopmental, cardiovascular, mental and general health, functional difficulties and social outcomes. Of 352 infants born to 290 maternal trial participants, we assessed 214 (61%; 96 (45%) female) at mean (standard deviation) age 20.5 (1.5) years. The rate of any asthma diagnosis was similar in both groups (58/107 (54%) repeat bethamethasone versus 50/107 (47%) placebo; risk ratio adjusted for gestational age at trial entry, multiplicity and birth centre 1.13, 95% confidence interval, 0.87, 1.46). Differences between the groups for the secondary outcomes were generally small and confidence intervals included the possibility of no difference between groups. CONCLUSIONS:In this follow-up of a randomised clinical trial, our data suggest neither major harm nor benefit for the offspring in early adulthood following exposure to repeat dose(s) of antenatal corticosteroids compared with a single course prior to 32 weeks' gestation. Smaller effects cannot be excluded and follow-up of adult offspring from other trials of repeat antenatal corticosteroids is recommended. TRIAL REGISTRATION:International Standard Randomized Controlled Trial, number ISRCTN48656428.

Late preterm infants (34+0 to 36+6 weeks’ gestation) account for 7

We assessed the use of magnesium sulphate prior to preterm birth for preventing cerebral palsy in an Australian and New Zealand registry study. Use increased markedly from 32.3% (2012) to 78.8% (2020) (p < 0.001). Binational approaches to sustain and explore the feasibility of further increasing use, informed by evolving evidence and guidelines, are needed.

Objective To investigate associations of the Fetal Pillow® with maternal and neonatal morbidity. Design Retrospective cohort. Setting Two tertiary maternity units, New Zealand. Population or Sample Full dilatation singleton, term, cephalic caesarean section, with three comparisons: at Unit A (1) before versus after introduction of the Fetal Pillow® (1 Jaunary 2016–31 October 2021); (2) with versus without the Fetal Pillow® after introduction (27 July 2017–31 October 2021); and (3) between Unit A and Unit B during the same time period (1 January 2019–31 October 2021). The Fetal Pillow® is unavailable at Unit B. Methods Cases were ascertained and clinical data were extracted from electronic clinical databases and records. Outcome data were adjusted and presented as adjusted odds ratios (aOR) with 95% CI. Main Outcome Measures Primary outcome “any” uterine incision extension; secondary outcomes included major extension (into adjacent structures), and a composite neonatal outcome. Results In all, 1703 caesareans were included; 375 with the device and 1328 without. Uterine incision extension rates were: at Unit A before versus after introduction: 26.8% versus 24.8% (aOR 0.88, 95% CI 0.65–1.19); at Unit A with the Fetal Pillow® versus without: 26.1% versus 23.8% (aOR 1.14, 95% CI 0.83–1.57); and at Unit A versus Unit B: 24.2% versus 29.2% (aOR 0.73, 95% CI 0.54–0.99). No differences were found in major extensions, or neonatal composite outcome. Conclusions Despite the relatively large size of this study, it could not rule out either a positive or a negative association between use of the Fetal Pillow® and uterine extensions, major uterine incision extensions, and neonatal morbidity. Randomised controlled trial evidence is required to assess efficacy.

OBJECTIVE:To determine the relationship between transient neonatal hypoglycemia in at-risk infants and neurocognitive function at 6-7 years of corrected age. STUDY DESIGN:The pre-hPOD Study involved children born with at least 1 risk factor for neonatal hypoglycemia. Hypoglycemia was defined as ≥1 consecutive blood glucose concentrations <47 mg/dl (2.6 mmol/L), severe as <36 mg/dl (2.0 mmol/L), mild as 36 to <47 mg/dL (2.0 to <2.6 mmol/L), brief as 1-2 episodes, and recurrent as ≥3 episodes. At 6-7 years children were assessed for cognitive and motor function (NIH-Toolbox), learning, visual perception and behavior. The primary outcome was neurocognitive impairment, defined as >1 SD below the normative mean in ≥1 Toolbox tests. The 8 secondary outcomes covered children's cognitive, motor, language, emotional-behavioral, and visual perceptual development. Primary and secondary outcomes were compared between children who did and did not experience neonatal hypoglycemia, adjusting for potential confounding by gestation, birthweight, sex and receipt of prophylactic dextrose gel (pre-hPOD intervention). Secondary analysis included assessment by severity and frequency of hypoglycemia. RESULTS:Of 392 eligible children, 315 (80%) were assessed at school age (primary outcome, n = 308); 47% experienced hypoglycemia. Neurocognitive impairment was similar between exposure groups (hypoglycemia 51% vs 50% no hypoglycemia; aRD -4%, 95% CI -15%, 7%). Children with severe or recurrent hypoglycemia had worse visual motion perception and increased risk of emotional-behavioral difficulty. CONCLUSION:Exposure to neonatal hypoglycemia was not associated with risk of neurocognitive impairment at school-age in at-risk infants, but severe and recurrent episodes may have adverse impacts. TRIAL REGISTRATION:Hypoglycemia Prevention in Newborns with Oral Dextrose: the Dosage Trial (pre-hPOD Study): ACTRN12613000322730.

The NIH Toolbox is used extensively in various research settings, including clinical trials, observational studies, and longitudinal studies. Its validity and reliability have been systematically appraised only in adults. The current study systematically evaluated the validity and reliability of the NIH Toolbox for assessing neurocognitive, motor and emotional-behavioral functioning in children. Based on 22 studies including over 60,000 participants, sufficient evidence was found for the validity and reliability of most tests in the Cognition Battery and Motor Battery. However, there was insufficient evidence to assess the validity and reliability of the Emotion Battery. Thus, this review supports the use of the NIH Toolbox Cognition and Motor Batteries in assessing neurocognitive functioning in 3-17-year-olds.

Gestational diabetes is the most common medical complication in pregnancy. Historically, gestational diabetes was considered a pregnancy complication involving treatment of rising glycaemia late in the second trimester. However, recent evidence challenges this view. Pre-pregnancy and pregnancy-specific factors influence gestational glycaemia, with open questions regarding roles of non-glycaemic factors in the aetiology and consequences of gestational diabetes. Varying patterns of insulin secretion and resistance in early and late pregnancy underlie a heterogeneity of gestational diabetes in the timing and pathophysiological subtypes with clinical implications: early gestational diabetes and insulin resistant gestational diabetes subtypes are associated with a higher risk of pregnancy complications. Metabolic perturbations of early gestational diabetes can affect early placental development, affecting maternal metabolism and fetal development. Fetal hyperinsulinaemia can affect the development of multiple fetal tissues, with short-term and long-term consequences. Pregnancy complications are prevented by managing glycaemia in early and late pregnancy in some, but not all women with gestational diabetes. A better understanding of the pathophysiology and heterogeneity of gestational diabetes will help to develop novel management approaches with focus on improved prevention of maternal and offspring short-term and long-term complications, from pre-conception, throughout pregnancy, and beyond.

In Māori and Pacific adults, the CREBRF rs373863828 minor (A) allele is associated with increased body mass index (BMI) but reduced incidence of type-2 and gestational diabetes mellitus. In this prospective cohort study of Māori and Pacific infants, nested within a nutritional intervention trial for pregnant women with obesity and without pregestational diabetes, we investigated whether the rs373863828 A allele is associated with differences in growth and body composition from birth to 12–18 months’ corrected age. Infants with and without the variant allele were compared using generalised linear models adjusted for potential confounding by gestation length, sex, ethnicity and parity, and in a secondary analysis, additionally adjusted for gestational diabetes. Carriage of the rs373863828 A allele was not associated with altered growth and body composition from birth to 6 months. At 12–18 months, infants with the rs373863828 A allele had lower whole-body fat mass [FM 1.4 (0.7) vs. 1.7 (0.7) kg, aMD −0.4, 95% CI −0.7, 0.0, P = 0.05; FM index 2.2 (1.1) vs. 2.6 (1.0) kg/m2 aMD −0.6, 95% CI −1.2,0.0, P = 0.04]. However, this association was not significant after adjustment for gestational diabetes, suggesting that it may be mediated, at least in part, by the beneficial effect of CREBRF rs373863828 A allele on maternal glycemic status.

Low blood concentrations of glucose (hypoglycaemia) soon after birth are common because of the delayed metabolic transition from maternal to endogenous neonatal sources of glucose. Because glucose is the main energy source for the brain, severe hypoglycaemia can cause neuroglycopenia (inadequate supply of glucose to the brain) and, if severe, permanent brain injury. Routine screening of infants at risk and treatment when hypoglycaemia is detected are therefore widely recommended. Robust evidence to support most aspects of management is lacking, however, including the appropriate threshold for diagnosis and optimal monitoring. Treatment is usually initially more feeding, with buccal dextrose gel, followed by intravenous dextrose. In infants at risk, developmental outcomes after mild hypoglycaemia seem to be worse than in those who do not develop hypoglycaemia, but the reasons for these observations are uncertain. Here, the current understanding of the pathophysiology of neonatal hypoglycaemia and recent evidence regarding its diagnosis, management, and outcomes are reviewed. Recommendations are made for further research priorities.

Background Antenatal corticosteroids for women at risk of preterm birth reduce neonatal morbidity and mortality, but there is limited evidence regarding their effects on long-term health. This study assessed cardiovascular outcomes at 50 years after antenatal exposure to corticosteroids. Methods and findings We assessed the adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) (1969 to 1974). The first 717 mothers received 2 intramuscular injections of 12 mg betamethasone or placebo 24 h apart and the subsequent 398 received 2 injections of 24 mg betamethasone or equivalent volume of placebo. Follow-up included a health questionnaire and consent to access administrative data sources. The co-primary outcomes were the prevalence of cardiovascular risk factors (any of hypertension, hyperlipidaemia, diabetes mellitus, gestational diabetes mellitus, or prediabetes) and age at first major adverse cardiovascular event (MACE) (cardiovascular death, myocardial infarction, coronary revascularisation, stroke, admission for peripheral vascular disease, and admission for heart failure). Analyses were adjusted for gestational age at entry, sex, and clustering. Of 1,218 infants born to 1,115 mothers, we followed up 424 (46% of survivors; 212 [50%] female) at mean (standard deviation) age 49.3 (1.0) years. There were no differences between those exposed to betamethasone or placebo for cardiovascular risk factors (159/229 [69.4%] versus 131/195 [67.2%]; adjusted relative risk 1.02, 95% confidence interval [CI] [0.89, 1.18;]; p = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; p = 0.261). There were also no differences in the components of these composite outcomes or in any of the other secondary outcomes. Key limitations were follow-up rate and lack of in-person assessments. Conclusions There is no evidence that antenatal corticosteroids increase the prevalence of cardiovascular risk factors or incidence of cardiovascular events up to 50 years of age. Established benefits of antenatal corticosteroids are not outweighed by an increase in adult cardiovascular disease.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

Objective: Gestational diabetes mellitus (GDM) is associated with offspring metabolic disease, including childhood obesity, but causal mediators remain to be established. We assessed the impact of lower versus higher thresholds for detection and treatment of GDM on infant risk factors for obesity, including body composition, growth, nutrition and appetite. Research design and methods: Prospective cohort study within the GEMS Trial; pregnant women were randomly allocated to detection of GDM using the lower criteria of the International Association of Diabetes and Pregnancy Study Groups or higher New Zealand criteria (ACTRN12615000290594). Randomly selected Control infants of women without GDM were compared with infants exposed to: A) GDM by lower but not higher criteria, with usual treatment for diabetes in pregnancy; B) GDM by lower but not higher criteria, untreated; C) GDM by higher criteria, treated. The primary outcome was whole-body fat mass at 5-6 months. Results: 760 infants enrolled; 432 assessed for the primary outcome. Fat mass was not significantly different between Controls (2.05kg) and exposure groups: A) GDM by lower but not higher criteria, treated (1.96kg), aMD -0.09 95%CI -0.29,0.10; B) GDM by lower but not higher criteria, untreated (1.94kg), aMD -0.15 95%CI -0.35,0.06; C) GDM detected and treated using higher thresholds (1.87kg), aMD -0.17 95%CI -0.37,0.03. Conclusion: GDM detected using lower but not higher criteria, was not associated with increased infant fat mass at 5-6 months, regardless of maternal treatment. GDM detected and treated using higher thresholds was also not associated with increased fat mass at 5-6 months.

INTRODUCTION:Antenatal corticosteroids are widely used to prevent morbidity and mortality after preterm birth, but there are ongoing concerns about the possible risk of long-term adverse effects, including perturbation of endocrine systems, with potential implications for reproduction. A small number of animal studies have suggested possible adverse effects on reproduction after antenatal exposure to corticosteroids, but there is a paucity of human data. MATERIAL AND METHODS:This is a secondary cohort analysis of the 50-year follow-up of the Auckland Steroid Trial (1969-1974) comparing antenatal exposure to corticosteroids or placebo. Participants whose mothers took part in the placebo-controlled randomized trial of antenatal corticosteroids completed a questionnaire reporting reproductive outcomes at 50 years of age. The main outcome was at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks. Additional outcomes included a number of pregnancies or fathered pregnancies ≥20 weeks, outcomes relating to female reproductive lifespan (including age at menarche and menopause), and outcomes relating to their offspring (including birthweight and gestation). RESULTS:Of 917 eligible participants, 415 (45% of eligible) completed the questionnaire at a mean (SD) age of 49.3 (1.0) years. The proportion of participants who had experienced at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks was similar in betamethasone and placebo-exposed groups (163/217 [75%] vs. 136/190 [72%]; RR 1.08, (95% CI 0.95 to 1.22); p = 0.23). Participants exposed to betamethasone had a slightly higher number of pregnancies or fathered pregnancies ≥20 weeks compared to those exposed to placebo (mean 1.89 vs. 1.60; marginal mean difference 0.20, (95% CI 0.03-0.37); p = 0.03). Other outcomes, including female reproductive lifespan and offspring-related outcomes, were similar in both randomized groups. There were also no differences in any outcomes between those born preterm and those born at term. CONCLUSIONS:Antenatal exposure to corticosteroids appears to have no clinically important effect on reproductive outcomes to 50 years.

Introduction Infants with severe or recurrent transitional hypoglycaemia continue to have high rates of adverse neurological outcomes and new treatment approaches are needed that target the underlying pathophysiology. Diazoxide is one such treatment that acts on the pancreatic β-cell in a dose-dependent manner to decrease insulin secretion.Methods and analysis Phase IIB, double-blind, two-arm, parallel, randomised trial of diazoxide versus placebo in neonates ≥35 weeks’ gestation for treatment of severe (blood glucose concentration (BGC)<1.2 mmol/L or BGC 1.2 to <2.0 mmol/L despite two doses of buccal dextrose gel and feeding in a single episode) or recurrent (≥3 episodes <2.6 mmol/L in 48 hours) transitional hypoglycaemia. Infants are loaded with diazoxide 5 mg/kg orally and then commenced on a maintenance dose of 1.5 mg/kg every 12 hours, or an equal volume of placebo. The intervention is titrated from the third maintenance dose by protocol to target BGC in the range of 2.6–5.4 mmol/L. The primary outcome is time to resolution of hypoglycaemia, defined as the first point at which the following criteria are met concurrently for ≥24 hours: no intravenous fluids, enteral bolus feeding and normoglycaemia. Groups will be compared for the primary outcome using Cox’s proportional hazard regression analysis, expressed as adjusted HR with a 95% CI.Ethics and dissemination This trial has been approved by the Health and Disability Ethics Committees of New Zealand (19CEN189). Findings will be disseminated in peer-reviewed journals, to clinicians and researchers at local and international conferences and to the public.Trial registration number ACTRN12620000129987.