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1: Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor (APOSTEL)

      Objective

      In women with threatened preterm labor a beneficial effect of sustained tocolysis has not been proven. We tested the hypothesis that sustained tocolysis reduces adverse perinatal outcome.

      Study Design

      We performed a multicenter, double-blind, placebo-controlled trial in all perinatal centers in The Netherlands (NTR 1336, www.ntr.nl). Between May 2008 and February 2010 women with preterm labor (26+0 and 32+2 weeks), who did not deliver after 48 hours tocolysis and a completed course of corticosteroids, were invited to participate. We excluded women with placenta previa, signs of intra-uterine infection, fetal distress, lethal congenital anomalies and maternal hypertensive diseases. After informed consent patients were randomly allocated to sustained tocolysis with nifedipine (80mg/day) or placebo for 12 days. Study medication was discontinued in case of intra-uterine infection or development of pre-eclampsia. The primary endpoint was adverse perinatal outcome, defined as a composite of perinatal death, chronic pulmonary dysplasia, necrotizing enterocolitis, neonatal sepsis, periventricular leucomalacia > grade I and intraventricular hemorrhage > grade II. Based on an expected 11% difference in adverse perinatal outcome, we randomized 406 patients (two-sided, α 0.05, β 0.80).

      Results

      Of 406 patients, 201 were allocated to nifedipine and 205 patients to placebo. Baseline characteristics in both groups were comparable. Gestational age at randomization was 29.2 weeks for both groups. Median prolongation of pregnancy was equal for both groups (4.8 weeks); Kaplan-Meier analysis indicated no difference in time interval to delivery (HR 1.0 [0.8 to 1.3]). Adverse perinatal outcome was not significantly different between the two groups, 9.3% in the nifedipine group and 11.6% in the placebo group (RR 0.81 [0.46 to 1.44]).

      Conclusions

      In women with threatened preterm labor, sustained tocolysis with nifedipine neither prolongs pregnancy, nor improves perinatal outcome.