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Neurodevelopmental Outcome After a Single Course of Antenatal Steroids in Children Born Preterm

A Systematic Review and Meta-analysis

Sotiriadis, Alexandros MD, PhD; Tsiami, Alexandra MD; Papatheodorou, Stefania MD, PhD; Baschat, Ahmet A. MD, PhD; Sarafidis, Kosmas MD, PhD; Makrydimas, George MD, PhD

doi: 10.1097/AOG.0000000000000748
Contents: Review

OBJECTIVE: To systematically review and integrate data on the neurodevelopmental outcome of children after administration of a single course of antenatal corticosteroids for threatened preterm labor.

DATA SOURCES: MEDLINE, Scopus, CENTRAL, and (inception to August 2014) using combinations of the terms “prenatal,” “antenatal,” “cortico*,” “*steroid*,” “betamethasone,” “dexamethasone,” “neurodevelopment*,” “*development*,” and “follow-up.” We perused the references of the retrieved articles.

METHODS OF STUDY SELECTION: We included randomized and nonrandomized trials reporting on the neurodevelopmental outcomes of children whose mothers were administered a single course of betamethasone or dexamethasone antenatally for threatened preterm birth as opposed to placebo or no treatment.

TABULATION, INTEGRATION, AND RESULTS: Summary risk ratio (RR) was calculated for dichotomous data; standardized mean difference was calculated for trials that measured the same outcome but used different methods. Heterogeneity was assessed using the I2 statistic. Sensitivity and subgroup analyses were planned according to study design, specific steroid, and mean gestational age at birth. A single course of antenatal corticosteroids was associated with reduced risk for cerebral palsy (seven studies; treated: 390 of 5,199, untreated: 146 of 1,379; RR 0.678, 95% confidence interval [CI] 0.564–0.815), psychomotor development index less than 70 (two studies; treated: 783 of 3,049, untreated: 258 of 969; RR 0.829, 95% CI 0.737–0.933), and severe disability (five studies; treated: 1,567 of 4,840, untreated: 475 of 1,211; RR 0.787, 95% CI 0.729–0.850). Steroid treatment increased the rates of intact survival (six studies; treated: 1,082 of 2,013, untreated: 273 of 561; RR 1.186, 95% CI 1.056–1.332). Betamethasone was found to significantly decrease the risk for severe disability and increase the rate of intact survival. Dexamethasone increased the rate of intact survival; however, data for dexametasone and the other planned subgroup analyses were limited (fewer than 1,000 children at most). The major limitations involved inclusion of nonrandomized studies and scarcity of data on finer neurodevelopmental outcomes.

CONCLUSION: A single course of antenatal corticosteroids in women at high risk for preterm birth appears to improve most neurodevelopmental outcomes in offspring born before 34 weeks of gestation.

A single course of antenatal corticosteroids in women at risk for preterm birth appears to improve most neurodevelopmental outcomes in offspring born before 34 weeks of gestation.

Second Department of Obstetrics and Gynecology and the First Department of Neonatology and Intensive Care Unit, Aristotle University of Thessaloniki, Thessaloniki, and the Department of Obstetrics and Gynecology, University of Ioannina, Ioannina, Greece; the Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus; and the Center for Fetal Therapy, Johns Hopkins University, Baltimore, Maryland.

Corresponding author: Alexandros Sotiriadis, MD, PhD, 92 Tsimiski Street, 54622 Thessaloniki, Greece; e-mail:

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.