Caroline A Crowther’s research while affiliated with University of Auckland and other places

BACKGROUND AND OBJECTIVES Preterm birth results in neonatal and childhood morbidity and mortality. Additionally, population-based studies show poorer cardiovascular health in adult survivors, but a full range of health outcomes has not been investigated into midlife. We aimed to assess the health outcomes after preterm vs term birth at 50 years in survivors of a randomized trial of antenatal betamethasone. METHODS Participants were asked to complete a health questionnaire and for consent to access administrative data. Participants deceased prior to follow-up were assessed with administrative data alone. The primary outcome was a composite: any of diabetes mellitus, prediabetes, treated hypertension, treated dyslipidemia, or a previous major adverse cardiovascular event. Secondary outcomes included respiratory, mental health, educational, and other health outcomes. RESULTS We included 470 participants: 424 assessed at mean age 49.3 years and 46 who died after infancy. The primary outcome occurred in 34.5% (112/325) of those born preterm and 29.9% (43/144) of those born at term; adjusted relative risk (aRR) 1.14 (95% CI, 0.85-1.54; P = .37). Cardiovascular events were less common in those born preterm (9/326 [2.8%] vs 10/144 [6.9%]; aRR 0.33, 95% CI, 0.14–0.79), while self-reported hypertension was more common (101/291 [34.7%] vs 23/116 [19.8%]; aRR 1.74, 95% CI, 1.16–2.61), although treated hypertension was not statistically significantly different (66/323 [20.4%] vs 22/143 [15.4%]; aRR 1.32, 95% CI, 0.84–2.06). Other components of the composite endpoint were similar between those born preterm and at term. CONCLUSIONS Those aged 50 years born preterm were more likely to have hypertension but had similar risk of diabetes, prediabetes, and dyslipidemia than those born at term, and their risk of cardiovascular events was lower.

In utero exposure to gestational diabetes mellitus (GDM) is associated with adverse long-term outcomes. Little is known about how mothers perceive these outcomes and the support they need for optimal outcomes for their children. We aimed to explore how women perceive the risk of adverse outcomes for their children exposed to GDM and the support they require for their optimal health. We conducted semistructured interviews with women who experienced GDM in at least one previous pregnancy. Data collection continued until saturation, and analysis followed an iterative thematic approach. Twenty-five mothers participated, and their perceptions about later outcomes for children exposed to GDM varied. Five themes were identified: relating GDM to the offspring’s later health; reactions to the potential for poor later outcomes; impact on child growth, development, and behavior; maintaining optimal health from childhood to adulthood; and recommendations for long-term care. Most mothers received no information about potential later child outcomes; some based their views on assumptions. Some mothers who believed their children were at increased risk of poor outcomes expressed fear and worry, while others proactively ensured their children engaged in healthy lifestyle choices. Mothers emphasized the need for support within health facilities (information provision, linking antenatal with child records, and risk assessment) and in the community (social groups, home visits) to ensure optimal health of their children. These findings have potential implications for policy and practice changes to optimize later health outcomes for children exposed to GDM.

Introduction: Hypoglycaemic neonates are usually admitted to neonatal intensive care for intravenous (IV) dextrose infusion if increased feeding and dextrose gel fail to restore normoglycaemia. However, the effectiveness of this intervention is uncertain. This review aimed to assess the evidence for the risks and benefits of IV dextrose for treatment of neonatal hypoglycaemia. Methods: Four databases and three clinical trial registries were searched from inception to October 5, 2023. Randomised controlled trials (RCTs), non-randomised studies of interventions, cohort studies, and before and after studies were considered for inclusion without language or publication date restrictions. Risk of bias was assessed using Cochrane's Risk of Bias 2 tool or Risk of Bias in Non-Randomized Studies of Interventions tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Meta-analysis was planned but not carried out due to insufficient data. Results: Across 6 studies (two RCTs and four cohort), 711 participants were included. Evidence from one cohort study suggests IV dextrose treatment may not be associated with neurodevelopmental impairment at ≥18 months of age (no effect numbers, p > 0.2; very low certainty evidence; 60 infants). Evidence from one RCT suggests IV dextrose treatment may reduce the likelihood of repeated hypoglycaemia (risk ratio [RR]: 0.67 [95% CI: 0.20, 2.18], p = 0.5; low certainty evidence; 80 infants) compared to treatment with oral sucrose bolus. However, the risk of a hyperglycaemic episode may be increased (RR: 2.33 [95% CI: 0.65, 8.39], p = 0.19; 80 infants). Conclusion: More evidence is needed to clarify the benefits and risks of IV dextrose for treatment of neonatal hypoglycaemia.

Background Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and later is associated with an increased risk of type 2 diabetes and other metabolic disorders. Consistent and evidence based postnatal care is key to improving maternal long-term health. We therefore aimed to review and compare recommendations of national and international clinical practice guidelines (CPG) for postnatal care after GDM and identify any evidence gaps in recommendations needing further research. Methods We searched five databases and forty professional organization websites for CPGs providing recommendations for postnatal care after GDM. CPGs which had full versions in English, endorsed, prepared, or authorized by a professional body, and published between 2013 and 2023 were eligible for inclusion. Two reviewers independently screened the articles, extracted the recommendations, and appraised the included CPGs using the Appraisal of Guidelines, Research, and Evaluation (AGREE) II tool. Results Twenty-six CPGs from 22 countries were included. Twelve CPGs (46%) were appraised as low quality with the lowest scoring domains being rigor of development and editorial independence. We found little high certainty evidence for most recommendations and few recommendations were made for maternal mental health and postpartum metabolic screening. Evidence gaps pertained to postpartum glucose screening, including frequency, tests, and ways to improve uptake, evaluation of effective uptake of lifestyle interventions, and ongoing long-term follow up care. Conclusions Most of the postnatal care recommendations in GDM guidelines are not based on high certainty evidence. Further efforts are needed to improve the global evidence base for postnatal care after GDM to improve long-term maternal health. Protocol Registration This review was registered in PROSEPRO (CRD42023454900).

Background Antenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids. Methods We assessed 424 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. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering. Results We assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations. Conclusions There is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.

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.

Background Neonatal hypoglycaemia is the most common metabolic disorder in infants, and may be influenced by maternal glycaemic control. This systematic review evaluated the effect of intrapartum maternal glycaemic control on neonatal hypoglycaemia. Methods We included randomised controlled trials (RCTs), quasi-RCTs, non-randomised studies of interventions, and cohort or case-control studies that examined interventions affecting intrapartum maternal glycaemic control compared to no or less stringent control. We searched four databases and three trial registries to November 2023. Quality assessments used Cochrane Risk of Bias 1 or the Effective Public Health Practice Project Quality Assessment Tool. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Meta-analysis was performed using random-effects models analysed separately for women with or without diabetes. The review was registered prospectively on PROSPERO (CRD42022364876). Results We included 46 studies of women with diabetes and five studies of women without diabetes: one RCT, 32 cohort and 18 case-control studies (11,273 participants). For women with diabetes, the RCT showed little to no difference in the incidence of neonatal hypoglycaemia between tight versus less tight intrapartum glycaemic control groups (76 infants, RR 1.00 (0.45, 2.24), p = 1.00, low certainty evidence). However, 11 cohort studies showed tight intrapartum glycaemic control may reduce neonatal hypoglycaemia (6,152 infants, OR 0.44 (0.31, 0.63), p < 0.00001, I² = 58%, very low certainty evidence). For women without diabetes, there was insufficient evidence to determine the effect of tight intrapartum glycaemic control on neonatal hypoglycaemia. Conclusions Very uncertain evidence suggests that tight intrapartum glycaemic control may reduce neonatal hypoglycaemia in infants of women with diabetes. High-quality RCTs are required.

OBJECTIVE To systematically review the evidence for the effectiveness and safety of magnesium sulfate as a fetal neuroprotective agent when given to individuals at risk of preterm birth. DATA SOURCES We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (through March 17, 2023), and reference lists of relevant studies. METHODS OF STUDY SELECTION Randomized controlled trials (RCTs) assessing magnesium sulfate for fetal neuroprotection in pregnant participants at risk of imminent preterm birth were eligible. Two authors assessed RCTs for inclusion, extracted data, and evaluated risk of bias, trustworthiness, and evidence certainty (GRADE [Grading of Recommendations Assessment, Development and Evaluation]). TABULATION, INTEGRATION, AND RESULTS We included six RCTs (5,917 pregnant participants and 6,759 fetuses at less than 34 weeks of gestation at randomization). They were conducted in high-income countries (two in the United States, two across Australia and New Zealand, and one each in Denmark and France) and commenced between 1995 and 2018. Primary outcomes: up to 2 years of corrected age, magnesium sulfate compared with placebo reduced the risk of cerebral palsy (risk ratio [RR] 0.71, 95% CI, 0.57–0.89; six RCTs, 6,107 children) and death or cerebral palsy (RR 0.87, 95% CI, 0.77–0.98; six RCTs, 6,481 children) (high-certainty evidence). Magnesium sulfate had little or no effect on death up to 2 years of corrected age (moderate-certainty evidence) or these outcomes at school age (low-certainty evidence). Although there was little or no effect on death or cardiac or respiratory arrest for pregnant individuals (low-certainty evidence), magnesium sulfate increased adverse effects severe enough to stop treatment (RR 3.21, 95% CI, 1.88–5.48; three RCTs, 4,736 participants; moderate-certainty evidence). Secondary outcome: magnesium sulfate reduced the risk of severe neonatal intraventricular hemorrhage (moderate-certainty evidence). CONCLUSION Magnesium sulfate for preterm fetal neuroprotection reduces cerebral palsy and death or cerebral palsy for children. Further research is required on longer-term benefits and harms for children, effect variation by participant and treatment characteristics, and the generalizability of findings to low- and middle-income countries. SYSTEMATIC REVIEW REGISTRATION The review protocol was based on a standard Cochrane Pregnancy and Childbirth template and our previous Cochrane Systematic Review (doi: 10.1002/14651858.CD004661.pub3; published before the introduction of PROSPERO).

( JAMA . 2023;330(7):603–614) Preterm infants have a greater risk of cerebral palsy, a common motor disability for which there is no cure. As such, primary prevention is especially important. The use of magnesium sulfate while pregnant has been shown in randomized clinical trials to be helpful for those at risk of early preterm delivery by improving an infant’s chance of survival without cerebral palsy. As a result, magnesium sulfate is recommended for fetal neuroprotection. However, there is a lack of data surrounding the ideal gestational age for using it prenatally.