Drug to prevent preterm labor does not improve neonatal outcomes
Key takeaways:
- There is no neonatal benefit or harm when using tocolytic drugs for threatened premature birth after 30 weeks’ gestation.
- Researchers said atosiban should be questioned as treatment for threatened preterm birth.
The contraction inhibitor atosiban prolonged labor in cases of threatened preterm birth beyond 30 weeks’ gestation but did not improve neonatal outcomes compared with placebo, researchers reported in The Lancet.
Atosiban, an oxytocin receptor antagonist, is a tocolytic drug indicated for the treatment of
threatened preterm birth. Although tocolytics have been shown to delay birth, benefits on neonatal outcomes have not been demonstrated, according to Larissa van der Windt, a doctoral student at Amsterdam UMC.
“We recommend clinicians alter their standard care for preterm labor to no longer administer atosiban and other tocolytics for threatened preterm birth above 30 weeks’ gestation,” van der Windt told Healio. “Our trial examined the effectiveness of atosiban. However, in our previous APOSTEL 3 study, which compared nifedipine with atosiban for threatened preterm birth, we did not find any benefit of nifedipine over atosiban. Therefore, our results are likely to be reflective of those expected from nifedipine.”
For the APOSTEL 8 study, researchers analyzed data from 755 women from 26 hospitals in the Netherlands, England and Ireland. All women had a singleton or twin pregnancy with threatened preterm birth from 30 to 33 weeks’ gestation and were randomly assigned IV atosiban (n = 375) or placebo (n = 377). Nine women did not receive atosiban or placebo because of progression of labor. The primary outcome was a composite of mortality (stillbirth and death up to 28 days postpartum) and six severe neonatal comorbidities.
The primary outcome occurred in 8% of infants in the atosiban group and 9% of infants in the placebo group, for a relative risk of 0.9 (95% CI, 0.58-1.4). There were seven infant deaths, including three in the intervention arm and four in the placebo arm; all deaths were deemed to be unrelated to the study drug. There were no between-group differences in maternal adverse events and no maternal deaths. Additionally, median pregnancy prolongation from inclusion until birth did not differ between the groups.
“This trial was designed to specifically look at those women with threatened preterm birth between 30- and 34-weeks’ gestation,” Martijn Oudijk, MD, PhD, professor of prevention and treatment of premature birth at Amsterdam UMC, told Healio. “Outcomes might be different for lower gestational ages. To investigate tocolytic drugs at lower gestational ages from 24 to 30 weeks’ gestation would be a next logical step for research.”
In a press release, the researchers noted that use of tocolytic drugs after 30 weeks’ gestation has already been discontinued in large hospitals in Canada and Ireland.
“It is high time we start working on adjusting guidelines, both in the Netherlands and abroad,” Oudijk said in the release.
For more information:
Martijn Oudijk, MD, PhD, can be reached m.oudijk@amc.uva.nl. at Larissa van der Windt can be reached at l.i.vanderwindt@amsterdamumc.nl.