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Original Contribution
January 2, 2013

Effect of Maintenance Tocolysis With Nifedipine in Threatened Preterm Labor on Perinatal Outcomes: A Randomized Controlled Trial

Author Affiliations

Author Affiliations: Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (Drs Roos, Spaanderman, and Lotgering); Department of Epidemiology, Julius Center for Health Sciences and Primary Care (Mr Schuit), and Department of Obstetrics and Gynecology (Drs Kwee and Oudijk), University Medical Center Utrecht, Utrecht, the Netherlands; Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, the Netherlands (Drs Bloemenkamp and Scherjon); Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, the Netherlands (Drs Bolte and de Groot); Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, the Netherlands (Drs Cornette and Duvekot); Department of Obstetrics and Gynecology, Isala Clinics, Zwolle, the Netherlands (Drs van Eyck and Nij Bijvank); Department of Obstetrics and Gynecology, University Medical Center, Groningen, the Netherlands (Drs Franssen, van Pampus, and Sollie); Departments of Neonatology (Dr Kok), and Obstetrics and Gynecology (Ms Vijgen and Drs Mol and van der Post), and Clinical Research Unit (Dr Opmeer), Academic Medical Center, Amsterdam, the Netherlands; Department of Obstetrics and Gynecology, Máxima Medical Center, Veldhoven, the Netherlands (Drs Merién and Porath); Department of Obstetrics and Gynecology, Amphia Hospital, Breda, the Netherlands (Dr Papatsonis); and Department of Obstetrics and Gynecology, Maastricht University Medical Center, GROW School for Oncology and Developmental Biology, Maastricht, the Netherlands (Drs Scheepers and Willekes).

JAMA. 2013;309(1):41-47. doi:10.1001/jama.2012.153817

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.