Nifedipine-Maintained Tocolysis Doesn't Alter Birth Outcomes

Barbara Boughton

January 01, 2013

In a study of 406 Dutch women with symptoms of preterm labor, maintenance tocolysis with the calcium-channel blocker nifedipine failed to reduce adverse perinatal outcomes when compared with placebo, according to a study published in the January 2, 2013, issue of JAMA.

Nifedipine given for 12 days was not associated with a decline in a composite endpoint that included perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage grade 3 or higher, periventricular leukomalacia above grade 1, or necrotizing enterocolitis.

Carolien Roos, MD, from Radboud University Nijmegen Medical Centre in the Netherlands, and colleagues compared nifedipine with placebo for maintenance treatment among women with threatened preterm labor who had not delivered after 48 hours of tocolysis. The randomized controlled trial was conducted in 11 perinatal units in tertiary care centers in the Netherlands from 2008 to 2010.

The investigators randomly assigned women who had not delivered after initial tocolysis for 48 hours to receive treatment with either 20 mg of nifedipine slow-release tablets every 6 hours, for a total daily dose of 80 mg nifedipine, or placebo for 12 days. Physicians, however, could increase the dosing intervals to every 4 hours. Infants who survived birth were followed up for up to 6 months after birth.

Results indicate that adverse perinatal outcomes, as assessed by the composite endpoint, were not significantly different in the nifedipine group when compared with placebo (11.9% [95% confidence interval (CI), 7.5% - 16.4%] vs 13.7% [95% CI, 9.0%-18.4%]; relative risk, 0.87; 95% CI, 0.53 - 1.45).

Five infants in the nifedipine group (2.5%) died vs 4 in the placebo group (2.0%). The gestational age and birth weights of infants born to women receiving nifedipine and those receiving placebo were also similar. In addition, there was no significant difference between the 2 treatment groups in the numbers of neonatal intensive care unit admissions, length of intensive care unit treatment, or total length of hospital stay.

The lower-than-expected number of adverse outcomes in the placebo group might imply that maintenance tocolysis with nifedipine might have some benefit, the researchers acknowledge. However, the study's findings also confirm the results of earlier trials on nifedipine as well as other commonly used tocolytics, showing that all were ineffective in prolonging pregnancy or improving perinatal outcomes, the researchers note.

Thus, treatment with a uterine relaxant may not be a real solution for preterm labor when used as maintenance therapy, the authors write. "Future research should be directed toward therapies tailored to the specific underlying causes of preterm labor," they conclude.

The study was funded by ZonMw, the Netherlands Organization for Health Research, and the Development Healthcare Efficiency Program. One coauthor reports receipt of a grant or pending grant and payment for manuscript preparation from CSL Behring. One coauthor reports provision of expert testimony for the Dutch courts, payment for lectures including service on speakers bureaus from Dutch training institutions, royalties for a Dutch textbook on obstetrics, and stocks/stock options that are private and unrelated. The other authors have disclosed no relevant financial relationships.

JAMA. 2013;309:41-47.