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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., Author(s): Anthony G. B. Walters 1, Greg D. Gamble 1, Caroline A. Crowther 1, Stuart R. Dalziel 2,3, Carl L. Eagleton 1, Christopher J. D. McKinlay 2, Barry J. Milne [...]

Introduction: A combination of self-reported questionnaire and administrative data could potentially enhance ascertainment of outcomes and alleviate the limitations of both in follow up studies. However, it is uncertain how access to only one of these data sources to assess outcomes impact study findings. Therefore, this study aimed to determine whether the study findings would be altered if the outcomes were assessed by different data sources alone or in combination. Methods: At 50-year follow-up of participants in a randomized trial, we assessed the effect of antenatal betamethasone exposure on the diagnosis of diabetes, pre-diabetes, hyperlipidemia, hypertension, mental health disorders, and asthma using a self-reported questionnaire, administrative data, a combination of both, or any data source, with or without adjudication by an expert panel of five clinicians. Differences between relative risks derived from each data source were calculated using the Bland-Altman approach. Results: There were 424 participants (46% of those eligible, aged 49 years, SD 1, 50% male). There were no differences in study outcomes between participants exposed to betamethasone and those exposed to placebo when the outcomes were assessed using different data sources. When compared to the study findings determined using adjudicated outcomes, the mean difference (limits of agreement) in relative risks derived from other data sources were: self-reported questionnaires 0.02 (-0.35 to 0.40), administrative data 0.06 (-0.32 to 0.44), both questionnaire and administrative data 0.01 (-0.41 to 0.43), and any data source, 0.01 (-0.08 to 0.10). Conclusion: Utilizing a self-reported questionnaire, administrative data, both questionnaire and administrative data, or any of these sources for assessing study outcomes had no impact on the study findings compared with when study outcomes were assessed using adjudicated outcomes. [ABSTRACT FROM AUTHOR]

Executive function plays an important role in promoting learning and social-emotional development in children. Neonatal hypoglycemia associates with executive function difficulties at 4.5 years, but little is known about the development of executive function over time in children born at risk of neonatal hypoglycemia. We aimed to describe the stability of executive function from early to mid-childhood in children born at risk of neonatal hypoglycemia and its association with neonatal hypoglycemia. Participants in a prospective cohort study of infants born at risk for neonatal hypoglycemia were assessed at ages 2, 4.5, and 9–10 years. We assessed executive function with batteries of performance-based and questionnaire-based measures, and classified children into one of four stability groups (persistent typical, intermittent typical, intermittent difficulty, and persistent difficulty) based on dichotomized scores (typical versus low at each age). Multinomial logistic regression was used to determine the associations between neonatal hypoglycemia and executive function stability groups. Three hundred and nine children, of whom 197 (64%) experienced neonatal hypoglycemia were assessed. The majority of children had stable and typical performance-based (63%) and questionnaire-based (68%) executive function across all three ages. Around one-third (30–36%) of children had transient difficulties, and only a few (0.3–1.9%) showed persistent difficulties in executive function at all ages. There was no consistent evidence of an association between neonatal hypoglycemia and the stability of executive function. Neonatal hypoglycemia does not appear to predict a specific pattern of development of executive function in children born at risk. [ABSTRACT FROM AUTHOR]

Background: Poor feeding, among other factors, predisposes neonates to hypoglycaemia. Early feeding is widely recommended to prevent hypoglycaemia in those at risk, but the effectiveness of this is uncertain. This review aimed to summarise and analyse the evidence on the effectiveness of early feeding for prevention of neonatal hypoglycaemia. Methods: Four databases and three clinical trial registries were searched from inception to May 24, 2023. Published and unpublished randomised controlled trials (RCTs), quasi-RCTs, cluster randomised trials, non-randomised studies of interventions, and observational studies with comparison groups were considered for inclusion with no language or publication date restrictions. We included studies of neonates who were fed early (within 60 min of birth or study defined) versus delayed. Study quality was assessed using the Cochrane Risk of Bias 1 tool or Effective Public Health Practice Project Quality Assessment tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RevMan 5.4.1 or R was used to synthesise results in random-effects meta-analyses. This review was registered prospectively with PROSPERO (CRD42022378904). Results: A total of 175,392 participants were included across 19 studies, of which two were RCTs, 14 cohort studies, two cross-sectional studies, and one a case-control study. Most studies (13/19) were conducted in low- or lower-middle-income countries. Early feeding may be associated with reduced neonatal hypoglycaemia (four cohort studies, 744 infants, odds ratio [OR] 0.19 (95% CI: 0.10–0.35), p < 0.00001, I2 = 44%) and slightly reduced duration of initial hospital stay (one cohort study, 1,673 infants, mean difference: –0.20 days [95% CI: −0.31 to −0.09], p = 0.0003), but the evidence is very uncertain. One RCT found early feeding had little or no effect on the risk of neonatal mortality, but three cohort studies found early feeding may be associated with reduced risk (136,468 infants, OR 0.51 [95% CI: 0.37–0.72]; low certainty evidence; p <0.0001; I2 = 54%). Conclusion: We found that early feeding may reduce the incidence of neonatal hypoglycaemia, but the evidence is very uncertain. Given its many other benefits, early feeding should continue to be recommended. This review was primarily funded by the Aotearoa Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health. [ABSTRACT FROM AUTHOR]

Purpose: There is uncertainty about the effect of increased neonatal protein intake on neurodevelopmental outcomes following preterm birth. The aim of this study was to assess the effect of a change in neonatal nutrition protocol at a major tertiary neonatal intensive care unit intended to increase protein intake on ophthalmic and visual development in school‐age children born very preterm. Methods: The study cohort comprised children (n = 128) with birthweight <1500 g or gestational age < 30 weeks born at Auckland City Hospital before (OldPro group, n = 55) and after (NewPro group, n = 73) a reformulation of parenteral nutrition that resulted in increased total protein intake during the first postnatal week and decreased carbohydrate, total parenteral fluid and sodium intake. Clinical and psychophysical vision assessments were completed at 7 years' corrected age, including visual acuity, global motion perception (a measure of dorsal stream function), stereoacuity, ocular motility and ocular health. Composite measures of favourable overall visual, binocular and functional visual outcomes along with individual vision measures were compared between the groups using logistic and linear regression models. Results: Favourable overall visual outcome did not differ between the two groups. However, global motion perception was better in the NewPro group (p = 0.04), whereas the OldPro group were more likely to have favourable binocular visual outcomes (60% vs. 36%, p = 0.02) and passing stereoacuity (p = 0.02). Conclusions: These results indicate subtle but complex associations between early neonatal nutrition after very preterm birth and visual development at school age. [ABSTRACT FROM AUTHOR]

Introduction: Concurrent diagnosis of gestational diabetes mellitus and mental disorders is associated with adverse outcomes for mother and child, but there is limited information about prevalence or which women are at risk. Material and methods: This study was a prospective cohort study of women with gestational diabetes from 10 hospitals in New Zealand who reported anxiety (6‐item Spielberger State–Trait Anxiety Inventory), depression (Edinburgh Postnatal Depression Scale) and health‐related quality of life (36‐Item Short‐Form General Health Survey) at time of gestational diabetes diagnosis (baseline), 36 weeks' gestation, and 6 months postpartum. Potential predictors were assessed using multivariable logistic regression. Results: Among 414 respondents, 17% reported anxiety, 16% vulnerability to depression and 27% poor mental health‐related quality of life at time of gestational diabetes diagnosis. At 36 weeks' gestation, prevalence decreased for vulnerability to depression (8%) and poor mental health‐related quality of life (20%). Younger maternal age, Pacific ethnicity, previous history of gestational diabetes, and older gestational age at time of gestational diabetes diagnosis were associated with poorer mental health outcomes. At 6 months postpartum the prevalence of mental disorders did not differ from in late pregnancy and they were associated with later gestational age at time of gestational diabetes diagnosis and elevated 2‐hour postprandial glucose concentrations. Conclusions: Perinatal mental disorders are common at time of diagnosis among women with gestational diabetes in New Zealand and had decreased by late pregnancy and at 6 months after birth. These disorders are more common among women with specific risk factors who may therefore benefit from additional support. [ABSTRACT FROM AUTHOR]

This article presents the findings of a qualitative study that examined the perspectives of adult offspring who participated in a randomized trial during their mother's pregnancy. The study aimed to understand their views on consent, assent, and their priorities regarding health outcomes. The participants generally found the current consent procedures acceptable, highlighting the role of parents as decision-makers in pediatric research. The study emphasizes the importance of giving children a voice and involving them in the research process, as well as providing accurate information to research participants. The participants had diverse reasons for participating in the study and provided suggestions for improvement. The article acknowledges the limitations of the study and suggests ways to promote children's agency in research. [Extracted from the article]

Background: There is no consensus on optimal nutrition for preterm infants, leading to substantial practice variation. We aimed to assess the quality of nutrition guidelines for preterm infants, the consistency of recommendations, and the gaps in recommendations. Methods: We searched databases and websites for nutrition guidelines for preterm infants before first hospital discharge, which were endorsed, prepared, or authorized by a regional, national, or international body, written in English, and published between 2012 and 2023. Two reviewers independently screened articles and extracted the recommendations. Four reviewers appraised the included guidelines using Appraisal of Guidelines, Research, and Evaluation II. Results: A total of 7051 were identified, with 27 guidelines included, 26% of which were high in quality. Most guidelines lacked stakeholder involvement and rigor of development. We found considerable variation in recommendations, many of which lacked details on certainty of evidence and strength of recommendation. Recommendations for type of feed and breastmilk fortification were consistent among high‐quality guidelines, but recommendations varied for intakes of almost all nutrients and monitoring of nutrition adequacy. Different guidelines gave different certainty of evidence for the same recommendations. Most gaps in recommendations were due to very low certainty of evidence. Conclusion: Future development of nutrition guidelines for preterm infants should follow the standard guideline development method and ensure the rigorous process, including stakeholders' involvement, to improve the reporting of strength of recommendation, certainty of evidence, and gaps in recommendation. Evidence is needed to support recommendations about macro and micronutrient intakes, breastmilk fortification, and markers on adequacy of intake of different nutrients. [ABSTRACT FROM AUTHOR]

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: In this prospective cohort study within the Gestational Diabetes Mellitus Trial of Diagnostic Detection Thresholds (GEMS), 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; or C) GDM by higher criteria, treated. The primary outcome was whole-body fat mass at 5–6 months. RESULTS: There were 760 infants enrolled, and 432 were assessed for the primary outcome. Fat mass was not significantly different between control infants (2.05 kg) and exposure groups: A) GDM by lower but not higher criteria, treated (1.96 kg), adjusted mean difference (aMD) −0.09 (95% CI −0.29, 0.10); B) GDM by lower but not higher criteria, untreated (1.94 kg), aMD −0.15 (95% CI −0.35, 0.06); and C) GDM detected and treated using higher thresholds (1.87 kg), aMD −0.17 (95% CI −0.37, 0.03). CONCLUSIONS: 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. [ABSTRACT FROM AUTHOR]

Background Neonatal hypoglycemia is common and can cause brain injury. Buccal dextrose gel is effective for treatment of neonatal hypoglycemia, and when used for prevention may reduce the incidence of hypoglycemia in babies at risk, but its clinical utility remains uncertain. Methods and findings We conducted a multicenter, double-blinded, placebo-controlled randomized trial in 18 New Zealand and Australian maternity hospitals from January 2015 to May 2019. Babies at risk of neonatal hypoglycemia (maternal diabetes, late preterm, or high or low birthweight) without indications for neonatal intensive care unit (NICU) admission were randomized to 0.5 ml/kg buccal 40% dextrose or placebo gel at 1 hour of age. Primary outcome was NICU admission, with power to detect a 4% absolute reduction. Secondary outcomes included hypoglycemia, NICU admission for hypoglycemia, hyperglycemia, breastfeeding at discharge, formula feeding at 6 weeks, and maternal satisfaction. Families and clinical and study staff were unaware of treatment allocation. A total of 2,149 babies were randomized (48.7% girls). NICU admission occurred for 111/1,070 (10.4%) randomized to dextrose gel and 100/1,063 (9.4%) randomized to placebo (adjusted relative risk [aRR] 1.10; 95% CI 0.86, 1.42; p = 0.44). Babies randomized to dextrose gel were less likely to become hypoglycemic (blood glucose < 2.6 mmol/l) (399/1,070, 37%, versus 448/1,063, 42%; aRR 0.88; 95% CI 0.80, 0.98; p = 0.02) although NICU admission for hypoglycemia was similar between groups (65/1,070, 6.1%, versus 48/1,063, 4.5%; aRR 1.35; 95% CI 0.94, 1.94; p = 0.10). There were no differences between groups in breastfeeding at discharge from hospital (aRR 1.00; 95% CI 0.99, 1.02; p = 0.67), receipt of formula before discharge (aRR 0.99; 95% CI 0.92, 1.08; p = 0.90), and formula feeding at 6 weeks (aRR 1.01; 95% CI 0.93, 1.10; p = 0.81), and there was no hyperglycemia. Most mothers (95%) would recommend the study to friends. No adverse effects, including 2 deaths in each group, were attributable to dextrose gel. Limitations of this study included that most participants (81%) were infants of mothers with diabetes, which may limit generalizability, and a less reliable analyzer was used in 16.5% of glucose measurements. Conclusions In this placebo-controlled randomized trial, prophylactic dextrose gel 200 mg/kg did not reduce NICU admission in babies at risk of hypoglycemia but did reduce hypoglycemia. Long-term follow-up is needed to determine the clinical utility of this strategy. Trial registration ACTRN 12614001263684., Author(s): Jane E. Harding 1,*, Joanne E. Hegarty 1,2, Caroline A. Crowther 1, Richard P. Edlin 1, Gregory D. Gamble 1, Jane M. Alsweiler 2,3, for the hPOD Study Group [...]