In the management of threatened preterm birth between 30 and 34 weeks of gestation, atosiban falls short of improving neonatal outcomes when compared with placebo, according to the results of the APOSTEL 8 trial.

In the intention-to-treat-population, the primary outcome of a composite adverse neonatal outcome, which comprised perinatal mortality and morbidity, occurred in 8.2 percent of infants in the atosiban arm and in 9.2 percent of those in the placebo arm (relative risk [RR], 0.90, 95 percent confidence interval [CI], 0.58?1.40), reported lead researcher Dr Larissa van der Windt from University of Amsterdam in Amsterdam, Noord-Holland, Netherlands. [SMFM 2025, abstract 5]

Results were consistent in an analysis of the separate components of the primary outcome, van der Windt added. No significant differences between the atosiban and placebo arms were observed for perinatal mortality (0.4 percent vs 0.9 percent), bronchopulmonary dysplasia (0.4 percent vs 0.9 percent), necrotizing enterocolitis >stage 1 (0.4 percent vs 1.4 percent), respiratory distress syndrome (13.6 percent vs 16.3 percent), and NICU admission (34.3 percent vs 34.7 percent), among others.

In terms of obstetric outcomes, more atosiban-treated than placebo-treated women had their pregnancy prolonged beyond 48 hours (77.5 percent vs 69.2 percent). Antenatal corticosteroid course was completed in 75.7 percent and 68.2 percent of women, respectively. The rate of preterm birth (<37 weeks) was 69.6 percent in the atosiban arm and 68.2 percent in the placebo arm.

“The majority of guidelines recommend the use of tocolytic drugs in case of threatened preterm birth, although there are many differences concerning both the indications and types of tocolytic drugs recommended,” van der Windt noted.

However, none of the studies on tocolytic therapy for threatened preterm birth was ever able to demonstrate a positive effect on neonatal outcomes, she pointed out.

In light of the findings of APOSTEL 8, along with prior data, the established practice of standardized tocolytic administration in threatened preterm birth between 30 and 34 weeks of gestation might need to be reconsidered, according to van der Windt.

APOSTEL 8 was a double-blind placebo-controlled superiority trial conducted at 26 hospitals in the Netherlands, England, and Ireland. Between December 2017 and June 2023, a total of 755 women with a singleton or twin pregnancy and threatened preterm birth between 30 and 34 weeks' gestation were recruited for the trial. Threatened preterm birth was defined as the presence of regular uterine contractions coupled with a cervical length of <15 mm, cervical length of 13?30 and positive fibronectin/Actim Partus, or ruptured membranes.

The women were randomly assigned to receive intravenous atosiban or placebo for 48 hours. Two women in the atosiban arm were lost to follow-up and one in the placebo arm withdrew after randomization. The intention-to-treat population comprised 375 mothers with 449 infants in the atosiban arm and 377 mothers with 435 infants in the placebo arm. The mean maternal age was 30.6 years, and the median BMI was 23.4 kg/m². A total of 102 mothers had a history of preterm birth.

In subgroup analyses, the composite adverse neonatal outcome was documented in 8.0 percent of infants in the atosiban arm vs 10.7 percent in the placebo arm among mothers with singleton pregnancies, and in 8.8 percent vs 5.2 percent of infants, respectively, among mothers with twins. Among women with preterm premature rupture of the membranes, the primary outcome was reported in 15.6 percent vs 13.7 percent of infants in the atosiban vs the placebo arm, respectively.