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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., (© 2024. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shahbaz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Clinical practice guidelines recommend administering antenatal corticosteroids (ACS), either betamethasone or dexamethasone, to women at risk of preterm birth at less than 35 weeks' gestation. If women remain at risk of preterm birth seven or more days after an initial course of ACS, most guidelines recommend administration of a repeat dose(s). No randomised trials have assessed the efficacy of dexamethasone as a repeat steroid compared to betamethasone., Aim: We aimed to determine if there were differences between the use of dexamethasone or betamethasone as repeat ACS, for women who remain at risk of preterm birth after an initial course, on maternal, infant, and childhood health outcomes., Methods: We performed a secondary analysis of data from the ASTEROID randomised trial, where women at risk of preterm birth were allocated to either betamethasone or dexamethasone. Infant, childhood, and maternal outcomes were compared according to whether women received a repeat dose(s) of dexamethasone or betamethasone. The primary outcome was a composite outcome of death or any neurosensory disability at age two years (corrected for prematurity). The ASTEROID trial is registered with ANZCTR, ACTRN12608000631303., Results: 168 women and their infants were included, with 86 women receiving dexamethasone and 82 women receiving betamethasone as a repeat dose. Women in the two ACS groups had similar baseline characteristics. We observed little to no difference in the incidence of death or any neurosensory disability at age two years (OR 0.89, 95% CI 0.39 to 2.06, p = 0.79) or in the incidence of other infant, childhood, and maternal adverse health outcomes between women who received dexamethasone and those who received betamethasone., Conclusion: Use of dexamethasone for a repeat dose(s) compared to betamethasone did not result in any differences in infant, childhood, and maternal health outcomes. These results can be used to support clinical practice guideline recommendations., Competing Interests: The authors have declared that no competing interests exist.

Background: Antenatal corticosteroids given to women before preterm birth improve infant survival and health. However, whether dexamethasone or betamethasone have better maternal, neonatal, and childhood health outcomes remains unclear. We therefore aimed to assess whether administration of antenatal dexamethasone to women at risk of preterm birth reduced the risk of death or neurosensory disability in their children at age 2 years compared with betamethasone. We also aimed to assess whether dexamethasone reduced neonatal morbidity, had benefits for the mother, or affected childhood body size, blood pressure, behaviour, or general health compared with betamethasone., Methods: In this multicentre, double-blind, randomised controlled trial, we recruited pregnant women from 14 maternity hospitals in Australia and New Zealand that could provide care to preterm babies. Women were eligible for study inclusion if they were at risk of preterm birth before 34 weeks of gestation, had a singleton or twin pregnancy, and had no contraindications to antenatal corticosteroids. We randomly assigned women (1:1) to receive two intramuscular injections of either 12 mg dexamethasone (dexamethasone sodium phosphate) or 11·4 mg betamethasone (Celestone Chronodose), 24 h apart. The randomisation schedule used balanced, variable blocks that were stratified by hospital, gestational age, and number of fetuses (singleton or twins). We masked all participants, staff, and assessors to treatment groups. Analyses were by intention to treat. The primary outcome was death or neurosensory disability at age 2 years (corrected for prematurity). This study is registered with ANZCTR, ACTRN12608000631303., Findings: Between Jan 28, 2009, and Feb 1, 2013, we randomly assigned 1346 (78%) women who were pregnant with 1509 fetuses to groups: 679 (50%) women were assigned to receive dexamethasone and 667 (50%) women were assigned to receive betamethasone. 27 (4%) fetuses, infants, or children in the dexamethasone group and 28 (4%) fetuses, infants, or children in the betamethasone group died before age 2 years. The primary outcome of death or neurosensory disability at age 2 years was determined for 603 (79%) of 763 fetuses whose mothers received dexamethasone and 591 (79%) of 746 fetuses whose mothers received betamethasone. We found a similar incidence of death or neurosensory disability in the dexamethasone (198 [33%] of 603 infants) and betamethasone groups (192 [32%] of 591 infants; adjusted relative risk [adjRR] 0·97, 95% CI 0·83 to 1·13; p=0·66). 18 (3%) of 679 women in the dexamethasone group and 28 of 667 (4%) women in the betamethasone group reported side-effects. Discomfort at the injection site, the most frequent side-effect, was less likely in the dexamethasone group than in the betamethasone group (six [1%] women vs 17 [3%] women; p=0·02)., Interpretation: The incidence of survival without neurosensory disability at age 2 years did not differ between dexamethasone and betamethasone treatment. Our findings indicate that either antenatal corticosteroid can be given to women before preterm birth to improve infant and child health., Funding: National Health and Medical Research Council (Australia)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Importance: Repeated doses of antenatal betamethasone are recommended for women at less than 32 weeks' gestation with ongoing risk of preterm birth. However, concern that this therapy may be associated with adverse neurocognitive effects in children with fetal growth restriction (FGR) remains., Objective: To determine the influence of FGR on the effects of repeated doses of antenatal betamethasone on neurocognitive function in midchildhood., Design, Setting, and Participants: This preplanned secondary analysis of data from the multicenter Australasian Collaborative Trial of Repeat Doses of Corticosteroids (ACTORDS) included women at less than 32 weeks' gestation with ongoing risk of preterm birth (<32 weeks) at least 7 days after an initial course of antenatal corticosteroids who were treated at 23 hospitals across Australia and New Zealand from April 1, 1998, through July 20, 2004. Participants were randomized to intramuscular betamethasone or saline placebo; treatment could be repeated weekly if the woman was judged to be at continued risk of preterm birth. All surviving children were invited to a midchildhood outcome study. Data for this study were collected from October 27, 2006, through March 18, 2011, and analyzed from June 1 through 30, 2018., Interventions: At 6 to 8 years of corrected age, children were assessed by a pediatrician and psychologist for neurosensory and cognitive function, and parents completed standardized questionnaires., Main Outcomes and Measures: The prespecified primary outcomes were survival free of any disability and death or survival with moderate to severe disability., Results: Of 1059 eligible children, 988 (55.0% male; mean [SD] age at follow-up, 7.5 [1.1] years) were assessed at midchildhood. The FGR rate was 139 of 493 children (28.2%) in the repeated betamethasone treatment group and 122 of 495 (24.6%) in the placebo group (P = .20). Primary outcome rates were similar between treatment groups for the FGR and non-FGR subgroups, with no evidence of an interaction effect for survival free of any disability (FGR group, 108 of 144 [75.0%] for repeated betamethasone treatment vs 91 of 126 [72.2%] for placebo groups [odds ratio [OR], 1.1; 95% CI, 0.6-1.9]; non-FGR group, 267 of 335 [79.7%] for repeated betamethasone vs 283 of 358 [79.0%] for placebo groups [OR, 1.0; 95% CI, 0.7-1.5]; P = .77) and death or moderate to severe disability (FGR group, 21 of 144 [14.6%] for repeated betamethasone treatment vs 20 of 126 [15.9%] for placebo groups [OR, 0.9; 95% CI, 0.4-1.9]; non-FGR group, 29 of 335 [8.6%] for repeated betamethasone vs 36 of 358 [10.0%] for placebo [OR, 0.8; 95% CI, 0.4-1.3]; P = .84)., Conclusions and Relevance: In this study, repeated antenatal betamethasone treatment compared with placebo was not associated with adverse effects on neurocognitive function at 6 to 8 years of age, even in the presence of FGR. Physicians should use repeated doses of antenatal corticosteroids when indicated before preterm birth, regardless of FGR, in view of the associated neonatal benefits and absence of later adverse effects., Trial Registration: anzctr.org.au Identifier: ACTRN12606000318583.

Background: Repeat dose(s) of antenatal betamethasone are recommended for women at <32 weeks with ongoing risk of preterm birth. However, there is concern that use of repeat dose(s) in fetal growth restriction (FGR) may increase the risk of later cardiometabolic disease., Methods: We undertook secondary analysis of data from the Australasian Collaborative Trial of Repeat Doses of Corticosteroids Midchildhood Outcome Study to determine if FGR influences the effect of repeat betamethasone on growth and cardiometabolic function. At 6 to 8 years, children underwent anthropometry, dual energy x-ray absorptiometry, intravenous glucose tolerance testing, ambulatory blood pressure monitoring, and spirometry. FGR was defined as severe FGR at entry, cesarean delivery for FGR, or customized birth weight below the third centile., Results: Of 266 children assessed, FGR occurred in 43 of 127 (34%) exposed to repeat betamethasone and 44 of 139 (32%) exposed to placebo. There was an interaction between FGR and repeat betamethasone treatment for the effect on height ( z score mean difference [95% confidence interval]; FGR: 0.59 [0.01 to 1.17]; non-FGR: -0.29 [-0.69 to 0.10]; P = .01). However, FGR did not influence the effect of repeat betamethasone on cardiometabolic function, which was similar in treatment groups, both in FGR and non-FGR subgroups., Conclusions: Repeat antenatal betamethasone treatment had no adverse effects on cardiometabolic function, even in the presence of FGR. It may have a positive effect on height in FGR. Clinicians should use repeat doses of antenatal corticosteroids when indicated before preterm birth, regardless of FGR, in view of the associated neonatal benefits., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background and Objective: Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity, but could have adverse effects on skeletal development. We assessed whether exposure to repeat antenatal betamethasone alters bone mass in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids., Methods: Women were randomized to a single dose of betamethasone or placebo, ≥7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at <32 weeks' gestation. In this follow-up study, children underwent whole-body dual-energy radiograph absorptiometry at 6 to 8 years' corrected age., Results: Of 212 eligible childhood survivors, 185 were studied (87%; 91 repeat betamethasone group; 94 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar whole-body bone mineral content (median repeat betamethasone: 553 g, interquartile range: 442-712 g; placebo: 567 g, interquartile range: 447-750 g; geometric mean ratio: 0.99; 95% confidence interval: 0.94-1.03, P = .55) and bone area (median repeat betamethasone 832 cm 2 , interquartile range: 693-963 cm 2 ; placebo: 822 cm 2 , interquartile range: 710-1020 cm 2 ; geometric mean ratio: 0.99, 95% confidence interval: 0.92-1.07, P = .75)., Conclusions: Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not alter bone mass in mid-childhood., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Objective: To assess if exposure to repeat dose(s) of antenatal corticosteroids has beneficial effects on neurodevelopment and general health in mid-childhood, at 6 to 8 years' corrected age., Methods: Women at risk for very preterm birth, who had received a course of corticosteroids ≥7 days previously, were randomized to intramuscular betamethasone (11.4 mg Celestone Chronodose) or saline placebo, repeated weekly if risk of very preterm birth remained. Mid-childhood assessments included neurocognitive function, behavior, growth, lung function, blood pressure, health-related quality of life, and health service utilization. The primary outcome was survival free of neurosensory disability., Results: Of the 1059 eligible long-term survivors, 963 (91%) were included in the primary outcome; 479 (91%) in the repeat corticosteroid group and 484 (91%) in the placebo group. The rate of survival free of neurosensory disability was similar in both groups (78.3% repeat versus 77.3% placebo; risk ratio 1.00, 95% confidence interval, 0.94-1.08). Neurodevelopment, including cognitive function, and behavior, body size, blood pressure, spirometry, and health-related quality of life were similar in both groups, as was the use of health services., Conclusions: Treatment with repeat dose(s) of antenatal corticosteroids was associated with neither benefit nor harm in mid-childhood. Our finding of long-term safety supports the use of repeat dose(s) of antenatal corticosteroids, in view of the related neonatal benefits. For women at risk for preterm birth before 32 weeks' gestation, ≥7 days after an initial course of antenatal corticosteroids, clinicians could consider using a single injection of betamethasone, repeated weekly if risk remains., (Copyright © 2016 by the American Academy of Pediatrics.)

Background: It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial., Objectives: To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 January 2015), searched reference lists of retrieved studies and contacted authors for further data., Selection Criteria: Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth., Data Collection and Analysis: We assessed trial quality and extracted data independently., Main Results: We included 10 trials (a total of 4733 women and 5700 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, number needed to treat to benefit (NNTB) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNTB 30, 95% CI 19 to 79).Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) -75.79 g, 95% CI -117.63 to -33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.At early childhood follow-up, no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments. In women, for the two primary outcomes, there was no increase in infectious morbidity of chorioamnionitis or puerperal sepsis, and the likelihood of a caesarean birth was unchanged., Authors' Conclusions: The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.

Background: Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity but could have adverse long-term effects on cardiometabolic health in offspring. We assessed whether exposure to repeat antenatal betamethasone increased risk factors for later cardiometabolic disease in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids., Methods: Women were randomized to betamethasone or placebo treatment, ≥ 7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at <32 weeks' gestation. In this follow-up study, children were assessed at 6 to 8 years' corrected age for body composition, insulin sensitivity, ambulatory blood pressure, and renal function., Results: Of 320 eligible childhood survivors, 258 were studied (81%; 123 repeat betamethasone group; 135 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar total fat mass (geometric mean ratio 0.98, 95% confidence interval [CI] 0.78 to 1.23), minimal model insulin sensitivity (geometric mean ratio 0.89, 95% CI 0.74 to 1.08), 24-hour ambulatory blood pressure (mean difference systolic 0 mm Hg, 95% CI -2 to 2; diastolic 0 mm Hg, 95% CI -1 to 1), and estimated glomerular filtration rate (mean difference 1.2 mL/min/1.73 m(2), 95% CI -3.2 to 5.6)., Conclusions: Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not increase risk factors for cardiometabolic disease at early school age., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Both dexamethasone and betamethasone, given to women at risk of preterm birth, substantially improve short-term neonatal health, increase the chance of the baby being discharged home alive, and reduce childhood neurosensory disability, remaining safe into adulthood. However, it is unclear which corticosteroid is of greater benefit to mother and child.This study aims to determine whether giving dexamethasone to women at risk of preterm birth at less than 34 weeks' gestation increases the chance of their children surviving free of neurosensory disability at two years' corrected age, compared with betamethasone., Methods/design: Design randomised, multicentre, placebo controlled trial.Inclusion criteria women at risk of preterm birth at less than 34 weeks' gestation with a singleton or twin pregnancy and no contraindications to the use of antenatal corticosteroids and who give informed consent.Trial entry & randomisation at telephone randomisation eligible women will be randomly allocated to either the dexamethasone group or the betamethasone group, allocated a study number and corresponding treatment pack.Study groups women in the dexamethasone group will be administered two syringes of 12 mg dexamethasone (dexamethasone sodium phosphate) and women in the betamethasone group will be administered two syringes of 11.4 mg betamethasone (Celestone Chronodose). Both study groups consist of intramuscular treatments 24 hours apart.Primary study outcome death or any neurosensory disability measured in children at two years' corrected age.Sample size a sample size of 1449 children is required to detect either a decrease in death or any neurosensory disability from 27.0% to 20.1% with dexamethasone compared with betamethasone, or an increase from 27.0% to 34.5% (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2)., Discussion: This study will provide high-level evidence of direct relevance for clinical practice. If one drug clearly results in significantly fewer deaths and fewer disabled children then it should be used consistently in women at risk of preterm birth and would be of great importance to women at risk of preterm birth, their children, health services and communities., Trial Registration Number: ACTRN12608000631303.

Background: It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial., Objectives: To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), searched reference lists of retrieved studies and contacted authors for further data., Selection Criteria: Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth., Data Collection and Analysis: We assessed trial quality and extracted data independently., Main Results: We included 10 trials (more than 4730 women and 5650 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, numbers needed to treat (NNT) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNT 30, 95% CI 19 to 79).Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) -75.79 g, 95% CI -117.63 to -33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.At early childhood follow-up no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments., Authors' Conclusions: The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.

Objective: The goal was to determine whether repeat prenatal corticosteroid treatment alters blood pressure and myocardial wall thickness in neonates., Methods: A randomized, double-blind, placebo-controlled trial was performed in a tertiary perinatal center. Mothers with a singleton, twin, or triplet pregnancy, at a gestational age of <32 weeks, who had received initial treatment with corticosteroid > or =7 days earlier and who were considered to be at continued risk of preterm birth were assigned randomly to receive additional weekly betamethasone or placebo treatment. One hundred forty-five infants born to 120 women were studied. Blood pressure in the first 4 weeks after birth or until hospital discharge and interventricular septal thickness and left ventricular posterior wall thickness in diastole 48 to 72 hours after birth were measured., Results: There were no differences in mean, systolic, or diastolic blood pressures between infants in the placebo and repeat steroid groups. Blood pressures of infants in both groups were similar to published normal values. There were no differences between groups in interventricular septal thickness or left ventricular posterior wall thickness in diastole. In comparison with published normal ranges, however, 24% of infants had interventricular septal thickness and 32% of infants had left ventricular posterior wall thickness of >95th percentile., Conclusion: Exposure to repeat prenatal corticosteroid treatment did not increase neonatal blood pressure or myocardial wall thickness in infants who remained at risk of very preterm birth > or =7 days after an initial course of corticosteroid treatment.

Background: We previously reported the results of a randomized, controlled trial showing that repeat doses of antenatal corticosteroids reduced the risk of respiratory distress syndrome and serious neonatal morbidity. However, data have not been available regarding longer-term effects of this treatment., Methods: Women who had received an initial course of corticosteroid treatment 7 or more days previously were randomly assigned to receive an intramuscular injection of corticosteroid (11.4 mg of betamethasone) or saline placebo; the dose was repeated weekly if the mother was still considered to be at risk for preterm delivery and the duration of gestation was less than 32 weeks. We assessed survival free of major neurosensory disability and body size of the children at 2 years of corrected age., Results: Of the 1085 children who were alive at 2 years of age, 1047 (96.5%) were seen for assessment (521 exposed to repeat-corticosteroid treatment and 526 exposed to placebo). The rate of survival free of major disability was similar in the repeat-corticosteroid and placebo groups (84.4% and 81.0%, respectively; adjusted relative risk, 1.04, 95% confidence interval, 0.98 to 1.10; adjusted P=0.20). There were no significant differences between the groups in body size, blood pressure, use of health services, respiratory morbidity, or child behavior scores, although children exposed to repeat doses of corticosteroids were more likely than those exposed to placebo to warrant assessment for attention problems (P=0.04)., Conclusions: Administration of repeat doses of antenatal corticosteroids reduces neonatal morbidity without changing either survival free of major neurosensory disability or body size at 2 years of age. (Current Controlled Trials number, ISRCTN48656428 [controlled-trials.com].)., (Copyright 2007 Massachusetts Medical Society.)

Unlabelled: Small birth size is associated with reduced adult bone mass. We determined if antenatal betamethasone exposure, birth weight, or prematurity affects peak bone mass in 174 adults. Antenatal betamethasone exposure did not. Lower birth weight and prematurity predicted reduced adult height. Slower fetal growth rather than prematurity predicted lower bone mass, but this lower bone mass was appropriate for reduced adult height., Introduction: Small size at birth is reported to be associated with lower bone mass in adulthood. However, previous studies have not distinguished the relative contributions of length of gestation and fetal growth to size at birth. Fetal exposure to excess glucocorticoids has been proposed as a core mechanism underlying the associations between birth size and later disease risk. Antenatal glucocorticoids are given to pregnant women at risk for preterm delivery for the prevention of neonatal respiratory distress syndrome in their infants. We determined the relationship of antenatal exposure to betamethasone, birth weight, and prematurity to peak bone mass and femoral geometry in the adult survivors of the first randomized trial of antenatal glucocorticoids., Materials and Methods: We studied 174 young adults (mean age, 31 years) whose mothers participated in a randomized trial of antenatal betamethasone. Mothers received two doses of intramuscular betamethasone or placebo 24 h apart. Two thirds of participants were born preterm (<37 weeks gestation). We measured indices of bone mass and size and derived estimates of volumetric density and bone geometry from DXA assessments of the lumbar spine, femur, and total body., Results: There were no differences between betamethasone-exposed and placebo-exposed groups in any of the lumbar spine, femur, or total body DXA measures. There was no effect of antenatal betamethasone on adult height, although leg length was increased relative to trunk length (p = 0.002). A lighter birth weight (p

Objectives: To determine if antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome alters psychological functioning and health related quality of life in adulthood., Design: Follow-up of the first and largest double blind, placebo controlled, randomised trial of a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome., Setting: Tertiary obstetric hospital in Auckland, New Zealand., Participants: 192 adult offspring, mean age 31 years, of mothers who took part in a randomised controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (87 exposed to betamethasone and 105 exposed to placebo)., Interventions: Mothers received two doses of betamethasone or placebo 24 hours apart., Main Outcome Measures: Cognitive functioning assessed with Wechsler abbreviated scale of intelligence; working memory and attention assessed with Benton visual retention test, paced auditory serial addition test, and Brown attention deficit disorder scale; psychiatric morbidity assessed with Beck depression inventory II, state-trait anxiety inventory, and schizotypy traits questionnaire; handedness assessed with Edinburgh handedness inventory; health related quality of life assessed with short form 36 health survey., Results: No differences were found between groups exposed to betamethasone and placebo in cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life., Conclusions: Prenatal exposure to a single course of betamethasone does not alter cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life in adulthood. Obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.

Background: Antenatal betamethasone treatment is widely used for the prevention of neonatal respiratory distress syndrome in preterm infants and substantially reduces neonatal mortality and morbidity. Fetal exposure to excess glucocorticoids has been proposed as one of the core mechanisms of the fetal origins of adult disease hypothesis. We assessed whether antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome affects cardiovascular risk factors at 30 years of age., Methods: We followed up at age 30 years 534 individuals whose mothers participated in a double-blind, placebo-controlled, randomised trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Mothers received two doses of betamethasone or placebo given by intramuscular injection 24 h apart. Follow-up assessments included anthropometry; measurement of blood pressure, blood lipids (after overnight fasting), and early morning cortisol levels; and a 75 g oral glucose tolerance test., Findings: There were no differences between those exposed to betamethasone and to placebo in body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, or history of cardiovascular disease. After a 75 g oral glucose tolerance test, participants exposed to betamethasone had higher plasma insulin concentrations at 30 min (60.5 vs 52.0 mIU/L; ratio of geometric means 1.16 [95% CI 1.03 to 1.31], p=0.02) and lower glucose concentrations at 120 min (4.8 vs 5.1 mmol/L; difference -0.26 mmol/L [-0.53 to 0.00], p=0.05) than did those exposed to placebo., Interpretation: Antenatal exposure to betamethasone might result in insulin resistance in adult offspring, but has no clinical effect on cardiovascular risk factors at 30 years of age. Thus, obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.

Objective: To determine whether prenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) alters blood pressure in childhood., Design: Prospective follow-up study of a randomized, double-blind, placebo-controlled trial., Setting: National Women's Hospital (Auckland, New Zealand)., Participants: Two hundred twenty-three 6-year-old children of mothers who presented with unplanned premature labor and took part in a randomized, controlled trial of prenatal betamethasone therapy for the prevention of neonatal RDS., Intervention: Mothers received 2 doses of betamethasone (12 mg) or placebo, administered through intramuscular injection, 24 hours apart., Main Outcome Measures: Systolic and diastolic blood pressure at 6 years of age., Results: Children exposed prenatally to betamethasone (n = 121) did not differ in systolic or diastolic blood pressure from children exposed to placebo (n = 102) (mean difference: systolic: -1.6 mm Hg; 95% confidence interval: -4.1 to 0.8 mm Hg; diastolic: -0.3 mm Hg; 95% confidence interval: -2.5 to 1.8 mm Hg)., Conclusion: Prenatal exposure to betamethasone for prevention of neonatal RDS does not alter blood pressure at 6 years of age.

Objectives: To determine the risk of fetal, neonatal and maternal mortality and morbidity for women and their infants who remained undelivered more than 7 days following a course of prenatal corticosteroids., Design: Systematic review., Population: Women who gave birth more than 7 days after a course of prenatal corticosteroids compared with women not administered corticosteroids., Methods: Seven randomised controlled trials were identified which reported outcomes for women and their babies who remained undelivered more than 7 days after exposure to a single course of corticosteroids compared with a placebo/no treatment group., Main Outcome Measures: Fetal, neonatal and maternal mortality and morbidity., Results: Seven trials involving 862 infants, 434 born to corticosteroid treated women and 428 to control women were included in this review. For corticosteroid treated infants there was no reduction in the risk of respiratory distress syndrome (relative risk (RR), 0.72; 95% confidence interval (CI), 0.49-1.07), or stillbirth (RR, 1.67; 95% CI, 0.86-3.25). However, there was a tripling in risk of death for liveborn corticosteroid treated infants (RR, 3.24; 95% CI, 1.32-7.96; P = 0.01), and a doubling in risk of perinatal mortality (RR, 2.13; 95% CI, 1.27-3.57; P < 0.01). Corticosteroid treated infants were born on average 5 days earlier than controls (95% CI, -9.15 to -0.85 days, P = 0.02). Their mothers were more likely to have chorioamnionitis (RR, 2.91; 95% CI, 1.25-6.74; P = 0.01)., Conclusions: Infants exposed to corticosteroids more than 7 days before birth had no reduction in risk of respiratory distress syndrome but increased perinatal mortality.

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. Anthony G B Walters and colleagues assess cardiovascular outcomes fifty years after antenatal exposure to betamethasone, in long-term follow-up of a randomised double-blind, placebo-controlled trial. Author summary: Why was this study done?: Antenatal corticosteroids (ANC) are given to pregnant persons at risk of preterm birth to reduce the risk of death and breathing difficulty for their offspring. Animal studies have shown later adverse effects of ANC on offspring, particularly on their cardiovascular health in adulthood. There is little robust evidence about long-term effects in humans. This study aimed to provide evidence about the long-term effects of ANC on offspring cardiovascular health in adulthood. What did the researchers do and find?: We assessed participants at 50 years of age who had been exposed to ANC or placebo during the first randomised clinical trial of this treatment. We compared cardiovascular disease and cardiovascular risk factors between those exposed to ANC and placebo in 424 participants (46% of those still alive), using a questionnaire and routinely collected administrative data. We found no differences in cardiovascular outcomes between those exposed to ANC and those who were not. What do these findings mean?: There is no evidence that ANC has adverse effects on the cardiovascular health outcomes of offspring up to 50 years of age. The main limitation was the follow-up rate of less than 50% and the use of health questionnaires and routinely collected data rather than in-person assessments. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions 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.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).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.Antenatal exposure to corticosteroids appears to have no clinically important effect on reproductive outcomes to 50 years. [ABSTRACT FROM AUTHOR]