Atosiban fails to improve neonatal outcomes in threatened preterm births between 30-34 weeks: Study

Tocolytic medications are commonly used to delay preterm birth. Atosiban, an oxytocin receptor antagonist, is one such tocolytic used for threatened preterm labor. However, the effect of atosiban on improving neonatal outcomes remains unclear. This randomized controlled trial aimed to determine whether atosiban is superior to placebo in reducing morbidity in women with threatened preterm birth between 30+0 and 33+6 weeks of gestation. The primary outcome was a composite of perinatal mortality and neonatal morbidity, while key secondary outcome was the occurrence of adverse maternal events. According to study results, there was no significant difference in neonatal outcomes between atosiban and placebo. Although this study was well done, it was limited by a low event rate, which may decrease the ability to detect smaller differences between groups.

This was an international, multicentre, randomised, double-blind, superiority trial conducted in 26 hospitals in the Netherlands, England, and Ireland. After written informed consent, women aged 18 years or older with a singleton or twin pregnancy with threatened preterm birth from 30+0 to 33+6 weeks of gestation were randomly assigned (stratified by centre, 1:1 ratio) to intravenous atosiban or placebo. The primary outcome was a composite of perinatal mortality (stillbirth and death until 28 days postpartum) and six severe neonatal morbidities. Analysis was by intention-to-treat. Treatment effect was estimated as relative risk (RR) with 95% CI. This trial was prospectively registered at EudraCT (2017-001007-72) and the Netherlands Trial Registry (NL-OMON54673), and is complete. Findings: Between Dec 4, 2017, and July 24, 2023, a total of 755 participants were randomly assigned, of whom 752 were included in the intention-to-treat analysis (atosiban n=375, placebo n=377). The primary outcome occurred in 37 (8%) of 449 infants in the atosiban group and 40 (9%) of 435 in the placebo group (RR 0·90 [95% CI 0·58–1·40]). There were three (0·7%) and four (0·9%) infants who died, respectively (RR 0·73 [0·16–3·23]); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups, and there were no maternal deaths. They did not demonstrate superiority of atosiban over placebo in improving neonatal outcomes as treatment for threatened preterm birth from 30+0 to 33+6 weeks of gestation. As the primary goal of tocolysis should be improvement of neonatal outcomes, our outcomes question the standardised use of atosiban as treatment for threatened preterm birth from 30+0 to 33+6 weeks of gestation. The findings should reduce practice variation across countries and will contribute to evidence-based treatment for patients with threatened preterm birth.