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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.

Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11-14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12-13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml-1·kg-1·min-1·ng-1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%-71% in NG-Prem vs. G-Prem and 42%-80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.

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: 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.

Administration of antenatal glucocorticoids to women at risk of preterm birth has major benefits for infants but the use of repeat dose(s) is controversial. We performed a systematic review of randomized trials, using standard Cochrane methodology, to assess the effectiveness and safety of 1 or more repeat doses given to women at risk of preterm birth 7 or more days after an initial course. Ten trials were included involving over 4730 women and 5700 infants. Treatment with repeat dose(s) compared with no repeat treatment reduced the risk of respiratory distress syndrome (risk ratio, 0.83; 95% confidence interval, 0.75-0.91) and serious neonatal morbidity (risk ratio, 0.84; 95% confidence interval, 0.75-0.94). At 2- to 3-year follow-up (4 trials, 4170 children), there was no evidence of either significant benefit or harm. Repeat doses of glucocorticoids should be considered in women at risk of preterm birth 7 or more days after an initial course, in view of the neonatal benefits., (Copyright © 2012 Mosby, Inc. All rights reserved.)

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.)

Objective: This study was undertaken to compare the effects of exposure to repeated courses of antenatal steroids with those of a single course on hypothalamic-pituitary-adrenal axis function., Study Design: Women at risk of premature delivery were assessed for entry into a randomized controlled trial of repeated courses of corticosteroids (ACTORDS). If a woman declined the randomized trial then consent was sought for collection of observational data. Baseline bloods for cortisol and adrenocorticotropic hormone levels were collected and in a subset of infants a metyrapone test performed., Results: In the 86 studied infants, cortisol and adrenocorticotropic hormone levels did not differ between those exposed to single and repeated courses of antenatal steroids (P = .53 and P = .15, respectively). Although cortisol levels fell in response to metyrapone (P = .03) this response was not different between the single and repeated course groups (P = .46)., Conclusion: Repeated courses of antenatal steroids do not cause important hypothalamic-pituitary-adrenal axis suppression in the neonate.

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.

Background: The use of postnatal corticosteroids to treat or prevent chronic lung disease is common in very preterm infants. Medullary nephrocalcinosis has been noted as a possible side effect., Objective: This prospective study was designed to assess the incidence of nephrocalcinosis in extremely preterm infants exposed to dexamethasone., Patients and Methods: A prospective study of extremely preterm infants, recruited to a randomized trial of dexamethasone treatment for chronic lung disease, was initiated. Infants had US of the renal tract scheduled on entry into the study, at day 28 and at discharge or at the corrected gestational age of 36 weeks., Results: Thirty-three infants were enrolled in the study. Birth weight ranged between 440 and 990 g and gestation between 24 and 28 weeks. Nine infants died and six had incomplete data. Because there was no difference in incidence of calcification between those on the short course and those on the long course of dexamethasone, analysis was made on the entire cohort. One infant had nephrocalcinosis at the time of the initial US examination on day 26 of life. By day 28, nephrocalcinosis was present in 31% of those with complete data. By discharge, or corrected gestational age of 36 weeks, US evidence of nephrocalcinosis was present in 15 (83%) of 18 infants. All infants had at least one course of an aminoglycoside antibiotic during the study. All infants had parenteral nutrition. Only four infants received furosemide more regularly than single doses. The longest course was 10 days, received by an infant who did not develop nephrocalcinosis., Conclusion: The incidence of nephrocalcinosis is high in this group of sick, extremely preterm infants. Dexamethasone may be a factor in the development of nephrocalcinosis. Future research should focus on the natural history of nephrocalcinosis in extremely preterm infants.

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.

Many studies have provided evidence for the hypothesis that size at birth is related to the risk of developing disease in later life. In particular, links are well established between reduced birthweight and increased risk of coronary heart disease, diabetes, hypertension and stroke in adulthood. These relationships are modified by patterns of postnatal growth. The most widely accepted mechanisms thought to underlie these relationships are those of fetal programming by nutritional stimuli or excess fetal glucocorticoid exposure. It is suggested that the fetus makes physiological adaptations in response to changes in its environment to prepare itself for postnatal life. These changes may include epigenetic modification of gene expression. Less clear at this time are the relevance of fetal programming phenomena to twins and preterm babies, and whether any of these effects can be reversed after birth. Much current active research in this field will be of direct relevance to future obstetric practice. [ABSTRACT FROM AUTHOR]

The article discusses the mechanisms of birth at term and preterm. The article suggests that the role of intraplacental prostaglandin E-2 in sheep as intermediate between the fetal and maternal events of parturition may be mimicked in human gestation by placental corticotrophin-releasing hormone. The importance of both cytokine and glucocorticoid pathways of increased prostaglandin production at the time of parturition is also discussed.

OBJECTIVEPreterm infants receiving dexamethasone for respiratory morbidity frequently suffer restricted growth. The aim of this study was to investigate the interactions between dexamethasone treatment regimen and circulating IGFBP-3 and IGF-I levels, and the associations between these variables and linear growth rate in preterm babies receiving dexamethasone for chronic lung disease of prematurity. DESIGNA randomised, unblinded, clinical trial of two different courses of dexamethasone: a 42-day tapering course (the long course) and a repeatable 3 day pulse course. PATIENTSForty preterm infants (19 in the pulse group, 21 in the long group) with a birthweight ≤ 1250 g who were ventilated at 7 days of age. MEASUREMENTSLower leg length was measured thrice weekly by knemometry, and IGFBP-3 and IGF-I levels were measured prior to commencing treatment, at 14 and 42 days of treatment and at 36 weeks postmenstrual age (PMA). Interactions between variables were analysed by stepwise regression analysis and analysis of covariance (ancova). Associations between variables were assessed by correlation coefficients. RESULTSIn an ancova, mean daily dose of dexamethasone/kg (MDDD) and treatment group both significantly influenced IGFBP-3 levels (P = 0·0009 and P = 0·017, respectively), and tended to influence IGF-I levels similarly (P = 0·098 and P = 0·07). MDDD also significantly influenced mean daily increase in lower leg length (MDILL; P < 0·01). IGFBP-3 and IGF-I levels were significantly related to MDILL (ancova: P < 0·01). The correlation coefficients for IGFBP-3 and IGF-I levels and MDILL were 0·2 and 0·3 (both P < 0·0001), respectively. IGFBP-3 and IGF-I levels were highly correlated (r2 = 0·52, P < 0·0001) and both increased significantly with increasing PMA (P < 0·0001). IGF-I levels were higher in females (P = 0·036). CONCLUSIONThis study provides evidence that the growth-restricting... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Antenatal corticosteroids: a time for more careful scrutiny of the indications?" in the previous issue.

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 mmHg, 95% CI 22 to 2; diastolic 0 mmHg, 95% CI 21 to 1), and estimated glomerular filtration rate (mean difference 1.2 mL/min/1.73m², 95% CI 23.2 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. [ABSTRACT FROM AUTHOR]