A Trial of 17 Alpha-Hydroxyprogesterone Caproate to Prevent Prematurity in Twins

Abstract

ABSTRACT

As recently as 2004, 12.5% of all live-born infants in the United States were delivered preterm, before 37 completed weeks of gestation. A recent trial showed that women with a previous spontaneous preterm birth who received weekly injections of 17 alpha-hydroxyprogesterone caproate (17P) had a one-third lower risk of recurrent preterm birth, but whether 17P can lower the rate in women with other risk factors is not clear. This placebo-controlled, double-blind, randomized, multicenter trial evaluated 17P in women carrying twins. Cases with serious fetal anomalies, detected by ultrasonography at 12–21 weeks' gestation, were excluded. Participants included 325 women given weekly intramuscular injections of 250 mg of 17P, starting at 16–20 weeks' gestation and ending at 35 weeks; and 330 placebo recipients. The primary outcome was delivery (or fetal death) before 35 weeks' gestation.

Compliance rates approximated 95% in both groups. The primary outcomes were the same in the actively treated and control groups, with respective preterm delivery rates of 41.5% and 37.3% and a relative risk (RR) of 1.1 (95% confidence interval [CI], 0.9–1.3). Nearly three-fourths of deliveries taking place before 35 weeks' gestation were spontaneous rather than medically indicated. Intervals to pregnancy loss, fetal death, or delivery were similar in the treatment and control groups, as were rates of obstetrical interventions. Rates of a composite outcome of serious adverse fetal or neonatal events were 20.2% in the 17P group and 18.0% in the placebo group (RR, 1.1; 95% CI, 0.9–1.5). Nearly two-thirds of women in each group had side effects, but they were, in general, mild and limited to the injection site.

The findings of this trial, which the investigators believe may be applied to most women in the US who are carrying twin pregnancies, fail to support the use of 17P for reducing the risk of preterm birth in twin gestations.