Nifedipine Versus Atosiban for Threatened Preterm Birth (APOSTEL III): A Multicenter, Randomized Controlled Trial

Abstract

Preterm birth is estimated to affect between 5% and 13% of all pregnancies and is the reason for more than 50% of neonatal morbidity and 50% and 75% of neonatal mortality cases worldwide. It causes long-term physical and developmental impairment, thus having a substantial burden on families and health care costs. A delay of delivery by 48 hours in cases with threatened preterm birth allows for the administration of antenatal corticosteroids, which improves neonatal outcomes. Therefore, treatment with tocolytics for 48 hours may prolong pregnancy long enough to optimize the beneficial effects of steroid administration. However, there is no consensus about which drug is most effective at improving neonatal outcomes while minimizing maternal risks. The aim of this study was to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. The APOSTEL III, multicenter randomized controlled trial was conducted in 10 tertiary and 9 teaching hospitals in the Netherlands and Belgium. Participants included women with threatened preterm birth (gestational age, 25–34 weeks). In this study, 254 women, from 2011 to 2014, were randomly assigned (1:1) to oral nifedipine and 256 to intravenous atosiban for 48 hours. The primary outcome included a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis. Data were analyzed in all women and babies, including during follow-up. The study revealed that the primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk, 0.91; 95% confidence interval, 0.61–1.37). A total of 16 babies (5%) died in the nifedipine group and 7 babies (2%) died in the atosiban group (relative risk, 2.20; 95% confidence interval, 0.91–5.33); all deaths were deemed unlikely to be related to the study drug. It is to be noted that maternal adverse events did not differ between the groups. The study concluded that in women with threatened preterm birth, 48 hours of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. It proposed that future clinical research must focus on large placebo-controlled trials powered for perinatal outcomes.