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Antenatal Corticosteroid Therapy Before 24 Weeks of Gestation: A Systematic Review and Meta-analysis

Park, Christina K. MSc; Isayama, Tetsuya MD; McDonald, Sarah D. MD, MSc

doi: 10.1097/AOG.0000000000001355
Contents: Review
Annual Awards

OBJECTIVE: To evaluate the effectiveness of antenatal corticosteroids compared with placebo or no treatment in neonates born before 24 weeks of gestation.

DATA SOURCES: We searched MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Central Register of Controlled Trials databases from 1990 to March 13, 2015, and

METHODS OF STUDY SELECTION: Studies considered were published randomized or quasirandomized controlled trials and observational studies that compared outcomes between neonates who received or did not receive antenatal corticosteroids born before 24 weeks of gestation.

TABULATION, INTEGRATION, AND RESULTS: We performed duplicate independent assessment of the title and abstracts, full-text screening, inclusion of articles, and data abstraction. We performed meta-analyses using random-effects models and quality assessment with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. There were 17 observational studies, and our primary outcome, mortality to discharge in neonates receiving active intensive treatment, had a total of 3,626 neonates. The adjusted odds of mortality to discharge were reduced by 52% in the antenatal corticosteroid group compared with the control group (crude adjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.36–0.56; adjusted OR 0.48, 95% CI 0.38–0.61; mortality to discharge 58.1% [intervention] compared with 71.8% [control]) with a “moderate” quality of evidence based on the GRADE system. There were no significant differences between the groups for severe morbidity.

CONCLUSION: The available data, all observational, show reduced odds of mortality to discharge in neonates born before 24 weeks of gestation who received antenatal corticosteroids and active intensive treatment. Antenatal corticosteroids should be considered for women at risk of imminent birth before 24 weeks of gestation who choose active postnatal resuscitation.

Supplemental Digital Content is Available in the Text.The odds of mortality to discharge are halved with antenatal corticosteroid therapy among neonates born before 24 weeks of gestation who receive active intensive treatment.

Departments of Clinical Epidemiology & Biostatistics, Obstetrics & Gynecology, and Radiology, McMaster University, Hamilton, and the Neonatal Intensive Care Unit, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.

Corresponding author: Sarah D. McDonald, MD, MSc, Department of Obstetrics and Gynecology, McMaster University, HSC 3N52B, 1280 Main Street, West, Hamilton, Ontario, Canada L8S 4K1; e-mail:

Financial Disclosure Ms. Park is supported by a Canadian Institutes of Health Research (CIHR) Training Program in Reproduction, Early Development and the Impact on Health (TGF-96122). Dr. McDonald is supported by a CIHR Canada Research Chair (950–229920). Dr. Isayama did not report any potential conflicts of interest.

The authors thank the authors of the primary studies who provided additional data for the meta-analyses: Drs. Abdel-Latif Mohamed and Kei Lui (New South Wales [NSW] and the Australian Capital Territory [ACT] NICUs Group); Dr. Cüneyt Tayman (Fatih Universitesi); Drs. David Bader and Brian Reichman (Israel Neonatal Network); Drs. Gustavo Rocha and Hercília Guimarães (Hospital de Sa[Combining Tilde]o Joa[Combining Tilde]o/Faculdade de Medicina, Universidade do Porto); Dr. José Figueras-Aloy (SEN1500 Spanish Neonatal Network); Dr. Karel Marsal (Extremely Preterm Infants in Sweden Study [EXPRESS] group); Dr. Lilia Vakrilova (Maichin Dom Neonatology Clinic), Drs. Matthew Laughon, Michael O'Shea (Extremely Low Gestational Age Newborn [ELGAN] study), Elizabeth Allred, and Alan Leviton (ELGAN study & Developmental Epidemiology Network); Dr. Reese Clark (Pediatrix Medical Group); Dr. Rintaro Mori (Neonatal Research Network Japan); and Dr. Soraya Abbasi and Mr. Emidio Sivieri (Pennsylvania Hospital, University of Pennsylvania). The authors also thank the following individuals who have assisted us with foreign language articles: Dr. Kari Tikkinen, Dr. Nigar Sekercioglu, Mr. Pavel Roshanov, Dr. Premsyl Bercik, and Ms. Sorina Stef. We value the contribution of Ms. Neera Bhatnager, BSc, MLIS, Head of Systems, Coordinator of Research and Graduate Education Support, Health Sciences Library, McMaster University, for her assistance in developing the search strategies.

© 2016 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.