Respiratory evolution after antenatal betamethasone dose reduction in very preterm neonates: a post hoc analysis of the BETADOSE trial.

Antenatal corticosteroids are used to accelerate fetal lung maturation. Recent studies suggest that the current dose may be too high. In the randomized multicenter BETADOSE trial, non-inferiority of the half dose compared to full dose was not shown for surfactant administration. Children with intra-uterine growth restriction have a higher risk of poor respiratory outcomes, including bronchopulmonary dysplasia, compared to those in other indications for antenatal corticosteroids. This post hoc study aims to compare respiratory outcomes between the half-dose and the full-dose groups in very preterm neonates, overall and according to indications for antenatal corticosteroids: inflammatory or vascular context including intra-uterine growth restriction. Eligible neonates were born < 32 weeks among those enrolled in the BETADOSE trial. The primary outcome was the occurrence of bronchopulmonary dysplasia. Multiple analyses adjusted for indications for antenatal corticosteroids, birthweight z-score, and gestational age were used. To account for multiple comparisons, p values were adjusted using the Bonferroni correction for the primary outcome. In the overall population and in the inflammatory context subgroup, there were no significant differences in respiratory outcomes, in particular surfactant use and bronchopulmonary dysplasia. The rate of discharge home with oxygen was higher in the half-dose group in the overall population. In neonates with intra-uterine growth restriction, surfactant use (63% vs 42%, p = 0.02) and bronchopulmonary dysplasia (40% vs 24%, p = 0.04) were more frequent in the half-dose group although no statistically significant difference was observed after correction using the Bonferroni method.

conclusionThe impact of reducing the dose of antenatal corticosteroids may vary according to the underlying indication for administration. No firm conclusions can be drawn from these findings, which may reflect residual confounding, particularly in the subgroup with intra-uterine growth restriction. As such, this observation should be considered exploratory and further prospective studies are needed. WHAT IS KNOWN: • Antenatal corticosteroids are used to accelerate fetal lung maturation. Recent studies question the current dose of betamethasone. The non-inferiority of the half compared to the full dose was not shown regarding the use of surfactant in the BETADOSE trial. WHAT IS NEW: • Few differences in in-hospital respiratory outcomes were found between the half-dose and the full-dose groups. A trend toward less favorable respiratory outcomes was observed among neonates exposed to the half dose.