Association of Antenatal Corticosteroids With Mortality, Morbidity, and Neurodevelopmental Outcomes in Extremely Preterm Multiple Gestation Infants

Abstract

Importance: Little is known about the effects of antenatal corticosteroids (ANS) on extremely preterm multiples.

Objective: To examine if use of ANS is associated with improvement in major outcomes in extremely preterm multiples.

Design, setting, and participants: Infants with a gestational age between 22 and 28 weeks born at a National Institute of Child Health and Human Development Neonatal Research Network center were studied between January 1998 and December 2013. Generalized estimating equation models were used to generate adjusted relative risks (aRR) controlling for important maternal and neonatal variables.

Exposure: Antenatal corticosteroids.

Main outcomes and measures: In-hospital mortality and the composite outcome of neurodevelopmental impairment at 18 to 22 months' corrected age or death before assessment.

Results: A total of 6925 multiple-birth infants were studied; 5775 of 6925 (83.4%) were twins, and 4276 (61.7%) were white. Of the total study population, 6094 (88%) were born to women who received ANS. In-hospital mortality was lower among infants with exposure to ANS vs no exposure (aRR = 0.87; 95% CI, 0.78-0.96). Neurodevelopmental impairment or death was not significantly lower among those exposed to ANS vs no exposure (aRR = 0.93; 95% CI, 0.84-1.03). Other adverse outcomes that occurred less frequently among infants of women receiving ANS included severe intraventricular hemorrhage (aRR = 0.68; 95% CI, 0.58-0.78) and the combined outcomes of necrotizing enterocolitis or death and severe intraventricular hemorrhage or death. Subgroup analyses indicated that exposure to ANS was associated with a lower risk of mortality and a lower composite of neurodevelopmental impairment or mortality among nonsmall for gestational age multiples (aRR = 0.82; 95% CI, 0.74-0.92; and aRR = 0.89; 95% CI, 0.80-0.98, respectively) and a higher risk among small for gestational age multiples (aRR = 1.40; 95% CI, 1.02-1.93; and aRR = 1.62; 95% CI, 1.22-2.16, respectively). Antenatal corticosteroids were associated with higher neurodevelopmental impairment or mortality among multiple-birth infants of mothers with diabetes (aRR = 1.55; 95% CI, 1.00-2.38) but not among infants of mothers without diabetes (aRR = 0.91; 95% CI, 0.83-1.01).

Conclusions and relevance: Compared with no exposure, exposure to ANS was associated with a lower risk of mortality in extremely preterm multiples, with no significant differences in the composite of neurodevelopmental impairment or death. Future research should investigate the increased risks of mortality and the composite of neurodevelopmental impairment or death associated with exposure to corticosteroids among small for gestational age multiples.

Figure 1

Frequency of Exposure to Antenatal Corticosteroids by Gestational Age and Year of Birth Among Multiples. Cells with fewer than 20 infants per gestational age per year of birth are not reported.

Figure 2

A. Adjusted relative risks by gestational age at 22–28 weeks for in-hospital mortality; B. Adjusted relative risks by gestational age at 22–28 weeks for neurodevelopmental impairment (NDI) or death at 18–22 months’ corrected age. Models adjusted for center, year of birth, maternal age (≤19 vs. ≥20 years), sex, race/ethnicity (black, white, or other), marital status, diabetes, hypertension, small for gestational age, and rupture of membrane more than 24 hours. Regression for NDI or death also adjusts for epoch and maternal education. ^aNot adjusted for center; model did not converge with center included. The error bars indicate 95% CIs.