OBJECTIVE: To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose–response relationship between number of courses of antenatal corticosteroids and neonatal size.
METHODS: This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken.
RESULTS: Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: −0.428 weeks, CI −0.10264 to −0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (−33.50 g, CI −66.27120 to −0.72880; P=.045), length (−0.339 cm, CI −0.6212 to −0.05676]; P=.019), and head circumference (−0.296 cm, −0.45672 to −0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference.
CONCLUSION: Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose–response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382.
LEVEL OF EVIDENCE: II
Infants exposed to multiple courses of antenatal corticosteroids are smaller and are born earlier than infants in the control group.
From the Departments of Obstetrics and Gynaecology and Paediatrics, Mount Sinai Hospital, the Program in Child Health Evaluative Sciences, SickKids Research Institute and Division of Biostatistics, the Departments of Obstetrics and Gynaecology and Newborn & Developmental Paediatrics and the Centre for Mother, Infant and Child Research, Sunnybrook Health Sciences Centre, the Departments of Physiology, Obstetrics and Gynecology, and Medicine, and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; the Department of Paediatrics and the Centre for Health Economics and Policy Analysis, and the Department of Clinical Epidemiology and Biostatistics, McMaster University Medical Centre, Hamilton, Ontario, Canada; the Departments of Obstetrics and Gynaecology, University of Calgary, Calgary, Alberta, Canada, BC Women's Hospital, University of British Columbia, Vancouver, British Columbia, Canada, and IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada; the Department of Gynecology-Obstetrics, Women's and Children's Hospital, State University of New York at Buffalo, Buffalo, New York; and the Division of Neonatology, Hospital for Sick Children, Toronto, Ontario, Canada.
* For a list of other members of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study collaborative group, see the Appendix online at http://links.lww.com/AOG/A296.
Supported by Canadian Institutes of Health Research grant number MCT 38142.
Corresponding author: Kellie E. Murphy, MD, MSc, FRCSC, FACOG, Mount Sinai Hospital, Maternal Fetal Medicine, Department of Obstetrics and Gynaecology, Third Floor Room 3097, Ontario Power Generation Building, 700 University Ave., Toronto, Ontario, M5R 1X5, Canada; e-mail: firstname.lastname@example.org.
Financial Disclosure The authors did not report any potential conflicts of interest.