Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate

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Preterm delivery before 37 completed weeks gestation remains the major factor influencing infant mortality in developed countries. Women who have had a spontaneous preterm delivery are at much higher risk for another suchdelivery in subsequent pregnancies. A reduced risk has been reported in women given 17 alpha-hydroxyprogesterone caproate (17P), a metabolite of progesterone. This multicenter trial evaluated 17P in pregnant women with a history of preterm birth in a previous pregnancy and a current pregnancy at 15 to 20 weeks. The preterm birth had occurred between 20 and 36 weeks 6 days of gestation, and was either spontaneous or a result of premature rupture of the fetal membranes. In a 2:1 ratio, 310 women were assigned to receive weekly intramuscular injections of 250 mg of 17P, whereas 153 received placebo injections. Injections continued until delivery or 36 weeks gestation. The groups were well matched except that placebo recipients had had more previous preterm deliveries. Delivery before 37 weeks gestation occurred in 36% of women given 17P and 55% of the placebo group. Deliveries before 35 weeks also were less frequent in the actively treated group, and deliveries before 32 weeks gestation were 42% less frequent with 17P. Survival analysis indicated significant prolongation of pregnancy with 17P. The adjusted relative risk of preterm delivery in the 17P group compared with placebo recipients was 0.70 (95% confidence interval, 0.57-0.85). It was estimated that only 5 to 6 women resembling those eligible for the present trial would have to be treated to prevent one preterm delivery in their current pregnancy. Miscarriages and stillbirths were slightly but not significantly more frequent in the 17P group. Active treatment significantly reduced the risk of a birth weight below 2500 g. It also lowered the risk of necrotizing enterocolitis, the need for supplemental oxygen, and the frequency of intraventricular hemorrhage (but not grade 3/4 hemorrhage). Weekly injections of the progestational substance 17P substantially lowered the risk of recurrent preterm delivery in these high-risk women.