NEW YORK (Reuters Health) – Administering 17-alpha-hyroxyprogesterone caproate to women with multiple pregnancy does not reduce the preterm birth rate or consequent neonatal morbidity, a Dutch study has shown.

“In fact, there were slightly more preterm births in the 17-alpha-hydroxyprogesterone caproate group as a whole,” the authors report in the September issue of Obstetrics & Gynecology.

Dr. Arianne C. Lim, with the Academic Medical Center in Amsterdam, and colleagues point out that prophylactic administration of progesterone can significantly reduce the incidence of preterm birth in women with a singleton pregnancy and a history of spontaneous preterm birth, but trials in women with multiple pregnancy have not shown the same benefit.

To investigate further, the team conducted a multicenter, double-blind, placebo-controlled randomized trial in 671 women with multiple pregnancy. Most had a twin pregnancy, but 17 had a triplet and one a quadruplet pregnancy. The participants were randomized to receive weekly injections of 250 mg 17-alpha-hyroxyprogesterone or placebo, starting at around 18 weeks of gestation.

The primary outcome measure was neonatal morbidity and mortality, a composite of severe respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage grade II B or worse, necrotizing enterocolitis, proven sepsis, and death before discharge from the hospital. Secondary measures were gestational age at delivery and preterm delivery.

The composite adverse outcome occurred in 16% of newborns in the progesterone group compared with 12% of those in the placebo group (RR 1.34), the investigators found.

Furthermore, the average gestational age at delivery was almost the same in the two groups, at 35.4 and 35.7 weeks, respectively. Rates of delivery before 28 weeks were 6% in the 17-alpha-hydroxyprogesterone caproate group and 5% in the placebo group.

Overall, there were there were more births before 37 weeks in the progesterone group (186) than in the placebo group (165), although the difference was not statistically significant.

“The possibility that progesterone has a harmful effect on multiple pregnancies should not be ruled out based on lack of statistical significance,” Dr. Lim and colleagues caution.

They add, “Although there is no clear explanation as to how progesterone can induce preterm birth, these findings should raise caution in researchers planning future studies on this intervention in multiple pregnancies.”

Obstet Gynecol 2011;118:513–520.