Survival without severe neonatal morbidity after antenatal betamethasone dose reduction: a post-hoc analysis of a randomized non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because non-inferiority of the half-dose on the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated.

OBJECTIVE: This study aimed to investigate, in infants born very preterm, the impact of antenatal betamethasone dose reduction on survival without severe neonatal morbidity recognized to be better correlated with long-term outcomes.

STUDY DESIGN: We performed a post-hoc secondary analysis of a randomized, multicentre, double blind, placebo-controlled, non-inferiority trial, testing half (11.4 mg once, n=1620) vs full (11.4 mg twice 24 hours apart, n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge in neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE-2, comprising one of the following morbidities: grade 3-4 intraventricular haemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-VEGF therapy or laser, and bronchopulmonary dysplasia.

RESULTS: After exclusion of women who withdrew consent or had pregnancy termination, and subjects lost to follow-up (8 in the half-dose group and 10 in the full-dose group), survival without severe neonatal morbidity was 300 of 451 (66.5%) vs 304 of 462 (65.8%) in neonates born before 32 weeks of gestation in the half-dose and full-dose group respectively (risk difference +0.7%; 95% confidence interval, -5.6 to +7.1]). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when either using two other internationally-recognized definitions of severe neonatal morbidity or considering the overall population recruited in the trial.

CONCLUSION: In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to either 11.4 mg or 22.8 mg antenatal betamethasone. Additional studies are needed to confirm these findings.