Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids: The ALPS Follow-up Study

The antenatal late preterm steroids (ALPSs) randomized trial found that antenatal exposure to betamethasone decreased short-term neonatal respiratory morbidity compared with placebo. But the trial also found an increased risk of neonatal hypoglycemia, which, when prolonged and persistent, is associated with adverse childhood neurodevelopment. While preclinical models have suggested that corticosteroids can have adverse effects on fetal brain development and childhood neurodevelopment, these findings have yet to be substantiated in individuals who receive corticosteroids in the late preterm period (34 to 36 weeks'). The aim of this study was to assess whether administration of late preterm corticosteroids affected neurodevelopmental outcomes in children 6 years of age or older. This was a prospective, follow-up study of the children of parents who participated in the ALPS trial, a double-blind, placebo-controlled trial conducted at Maternal-Fetal Medicine Units Network centers of the National Institute of Child Health and Human Development. Included in the ALPS trial were individuals at high risk of preterm delivery who were randomly assigned to receive 12 mg of intramuscular betamethasone for fetal lung maturity or placebo. Included in the follow-up study were the parents' children who were 6 years of age or older. The children participated in cognitive testing with psychologists who evaluated their general conceptional ability (GCA), verbal ability, nonverbal reasoning, and spatial ability. Gross motor function was also assessed. Questionnaires completed by the parents assessed the child's health, social abilities and traits of autism spectrum disorder, and behavioral and emotional issues. The primary outcome was the proportion of children with GCA scores <85. Of the 949 children included in the follow-up study, 479 had parents who received betamethasone and 470 who had parents who received placebos in the ALPS trial. The median age of the child was 7 years in each group (IQR, 6.5 to 7.7). The maternal and neonatal groups had similar characteristics, except in certain traits including neonatal hypoglycemia: The betamethasone group was more likely to have neonatal hypoglycemia than the placebo group. The proportion of children with a GCA score < 85 was not significantly different between the betamethasone and placebo groups (17.1% and 18.5%, respectively; adjusted risk ratio = 0.94; 95% confidence interval, 0.73 to 1.22). In post hoc sensitivity analysis, the proportion of GCA scores <85 remained similar between the 2 groups (18.1% and 20.3%; adjusted risk ratio = 0.92; 95% confidence interval, 0.71 to 1.25). Secondary outcomes assessing autistic traits, gross motor function, and emotional or behavioral problems also had no significant differences. In this follow-up study to ALPS, no significant differences were observed in the neurodevelopment of children born to individuals who received either betamethasone or placebo in the late preterm period.