Effect of maintenance tocolysis with nifedipine in threatened preterm labor on perinatal outcomes: A randomized controlled trial

Carolien Roos, Marc E A Spaanderman, Ewoud Schuit, Kitty W M Bloemenkamp, Antoinette C. Bolte, Jérôme Cornette, Johannes J J Duvekot, Jim Van Eyck, Maureen T M Franssen, Christianne J. De Groot, Joke H. Kok, Anneke Kwee, Ashley Merién, Bas Nij Bijvank, Brent C. Opmeer, Martijn A. Oudijk, Mariëlle G. Van Pampus, Dimitri N M Papatsonis, Martina M. Porath, Hubertina C J ScheepersSicco A. Scherjon, Krystyna M. Sollie, Sylvia M C Vijgen, Christine Willekes, Ben Willem J Mol, Joris A M Van Der Post, Fred K. Lotgering

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

Importance: In threatened preterm labor, maintenance tocolysis with nifedipine, after an initial course of tocolysis and corticosteroids for 48 hours, may improve perinatal outcome. Objective: To determine whether maintenance tocolysis with nifedipine will reduce adverse perinatal outcomes due to premature birth. Design, Setting, and Participants: APOSTEL-II (Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor) is a double-blind, placebo-controlled trial performed in 11 perinatal units including all tertiary centers in the Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks (plus 0 days) and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010). Intervention: Randomization assigned 406 women to maintenance tocolysis with nifedipine orally (80 mg/d; n=201) or placebo (n=205) for 12 days. Assigned treatment was masked from investigators, participants, clinicians, and research nurses. Main Outcome Measures: Primary outcome was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis). Analyses were completed on an intention-to-treat basis. Results: Mean (SD) gestational age at randomization was 29.2 (1.7) weeks for both groups. Adverse perinatal outcome was not significantly different between groups: 11.9% (24/201; 95% CI, 7.5%-16.4%) for nifedipine vs 13.7% (28/205; 95% CI, 9.0%-18.4%) for placebo (relative risk, 0.87; 95% CI, 0.53-1.45). Conclusions and Relevance: In patients with threatened preterm labor, nifedipine-maintained tocolysis did not result in a statistically significant reduction in adverse perinatal outcomes when compared with placebo. Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time. Trial Registration: trialregister.nl Identifier: NTR1336.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalJAMA - Journal of the American Medical Association
Volume309
Issue number1
DOIs
Publication statusPublished - 2 Jan 2013

ASJC Scopus subject areas

  • Medicine(all)

Cite this