The high rate of preterm delivery in the United States is the greatest contributor to the relatively high infant mortality rate in this country. Despite much effort, no effective method exists for prevention of preterm delivery. Progesterone has been studied as a prophylactic agent for preterm delivery with conflicting results. A meta-analysis of older trials using only 17 alpha-hydroxyprogesterone (17P) showed a significant protective effect. Meis and colleagues designed a multicenter modern retrial of 17P for prevention of pre-term delivery.
The authors screened patients for enrollment by reviewing prenatal charts of pregnancies at 15 to 20 weeks of gestation for a history of preterm delivery. Initial screening identified 2,980 women, of whom 1,039 were eligible after exclusion criteria, which included lack of documentation for prior preterm delivery, ultrasound dating of more than 20 weeks' gestation, planned cerclage, multifetal pregnancy, or prior progesterone use during the current pregnancy. After informed consent, 463 women (45 percent) agreed to participate in the trial. Fifty-nine percent were black, 26 percent were white, 14 percent were Hispanic, and 1 percent were from other groups. Almost one half of the enrolled women had a history of more than one preterm delivery. Outcome data were available for 99 percent of the pregnancies.
Spontaneous preterm delivery before 37 weeks' gestation among patients receiving placebo injections occurred in 45.1 percent but declined to 29.4 percent with 17P supplementation. The rate of preterm deliveries at less than 32 weeks' gestation was cut almost in half by treatment (19.6 percent of control pregnancies versus 11.4 percent of the 17P group). The reduction in preterm deliveries was similar across ethnic groups. The progesterone group showed significant reductions in birth weights below 2,500 g (5 lb 5 oz), necrotizing enterocolitis, and intraventricular hemorrhage. There were no apparent adverse effects to the prolongation of pregnancy achieved with 17P supplementation. Rates of chorioamnionitis and neonatal sepsis were similar between control and treatment groups.
The authors conclude that weekly injections of 17P reduced the rate of preterm delivery and decreased neonatal morbidity when used in women with a history of preterm delivery.