Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks' gestation

Abstract

Context: Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24 to 34 weeks' gestational age, but not before 24 weeks due to lack of data. However, many infants born before 24 weeks' gestation are provided intensive care.

Objective: To determine if use of antenatal corticosteroids is associated with improvement in major outcomes for infants born at 22 and 23 weeks' gestation.

Design, setting, and participants: Cohort study of data collected prospectively on inborn infants with a birth weight between 401 g and 1000 g (N = 10,541) born at 22 to 25 weeks' gestation between January 1, 1993, and December 31, 2009, at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4924 (86.5%) of the infants born between 1993 and 2008 who survived to 18 to 22 months. Logistic regression models generated adjusted odds ratios (AORs), controlling for maternal and neonatal variables.

Main outcome measures: Mortality and neurodevelopmental impairment at 18 to 22 months' corrected age.

Results: Death or neurodevelopmental impairment at 18 to 22 months was significantly lower for infants who had been exposed to antenatal corticosteroids and were born at 23 weeks' gestation (83.4% with exposure to antenatal corticosteroids vs 90.5% without exposure; AOR, 0.58 [95% CI, 0.42-0.80]), at 24 weeks' gestation (68.4% with exposure to antenatal corticosteroids vs 80.3% without exposure; AOR, 0.62 [95% CI, 0.49-0.78]), and at 25 weeks' gestation (52.7% with exposure to antenatal corticosteroids vs 67.9% without exposure; AOR, 0.61 [95% CI, 0.50-0.74]) but not in those infants born at 22 weeks' gestation (90.2% with exposure to antenatal corticosteroids vs 93.1% without exposure; AOR, 0.80 [95% CI, 0.29-2.21]). If the mothers had received antenatal corticosteroids, the following events occurred significantly less in infants born at 23, 24, and 25 weeks' gestation: death by 18 to 22 months; hospital death; death, intraventricular hemorrhage, or periventricular leukomalacia; and death or necrotizing enterocolitis. For infants born at 22 weeks' gestation, the only outcome that occurred significantly less was death or necrotizing enterocolitis (73.5% with exposure to antenatal corticosteroids vs 84.5% without exposure; AOR, 0.54 [95% CI, 0.30-0.97]).

Conclusion: Among infants born at 23 to 25 weeks' gestation, antenatal exposure to corticosteroids compared with nonexposure was associated with a lower rate of death or neurodevelopmental impairment at 18 to 22 months.

Conflict of interest statement

Disclosures

In addition to the NIH grant support to the institutions identified in the Acknowledgements, the coauthors have the following potential conflicts of interest to report:

Waldemar A. Carlo, MD – Mednax, board member.

Dennis Wallace, PhD - NICHD & NIAID, funding from multiple NICHD and NIAID cooperative agreements in which RTI acts as the data center or statistical center for NIH-funded research activities; Mead Johnson, Travel expenses paid for statistical presentation for Neonatal Fellows at the Southeastern meeting in February 2010; Kansas University Medical Center Research Foundation, Royalties paid annually for work use of a Stroke Rehabilitation scale in clinical trials. Scale was developed while I was on the faculty at Kansas University Medical Center during the period of 1995 thru 2000; amount is less than $200 per year; NIDDK, NIDA, Johns Hopkins, serve on 3 DSMBs for research funded by NIDA, NIDDK/NIAID (Type I DM) and the Gates foundation. For annual meetings of these DSMBs, I receive a $200 honorarium for a 1-day meeting and coverage of flight and hotels to attend meeting.

Edward F. Bell, MD - CRED Foundation (www.cred.ro) Reimbursement of economy class airfare to attend annual conference of the Romanian Neonatology Association as a speaker; University of Alabama at Birmingham, Birmingham, AL, Travel, accommodations, and honorarium for 2 days as visiting professor; Children’s Mercy Hospital, Kansas City, MO, Travel and honorarium for participation as speaker at conference; Portuguese Neonatal Society, Travel and accommodations for speaking at annual meeting.

Pablo J. Sanchez, MD - Collaborative Antiviral Study Group; F. Hoffman-LaRoche, Ltd; Astellas; NIDCD.

Krisa P. Van Meurs, MD – Consulting/honorarium and equipment support from Ikaria; Travel, accommodations, and meeting expenses paid for by Actelion and Ikaria; Payment for expert testimony for various law suits from legal firms.

Roger G. Faix, MD – Ikaria Biosynexus, Fellow grant review committee for Ikaria Chair of DSMB for Biosynexus; Yale University subcontract, NINDS grant for Genes and IVH.

Figures

Figure 1

Frequency of exposure of antenatal corticosteroids by gestational age and year of birth. The administration of antenatal corticosteroids increased over the 10 year period but remained lower at the lower gestational ages. Denominators for each data point are included in eTable 4.