Nearly 12 percent of pregnancies in the United States result in birth before 37 weeks’ gestation, and the incidence of such preterm births is slowly increasing. Most tocolytic treatments have not been effective beyond 48 hours in clinical trials. One explanation for this apparent lack of impact is that treatment is only begun once uterine activity has been confirmed. Sanchez-Ramos and colleagues reviewed the literature on an alternative strategy—prophylactic tocolysis using progesterone in women at high risk of preterm labor—to find the effectiveness of progesterone in preventing preterm birth in mothers at elevated risk and the impact of progesterone on perinatal morbidity and mortality.
The authors searched electronic databases, abstracts, and bibliographies and contacted experts in the field to identify all relevant studies. Studies included in the analysis had to use an outcome measure of delivery before 37 weeks’ gestation, threatened pre-term labor, birth weight less than 2,500 g, perinatal mortality, or respiratory distress syndrome. Studies were independently rated for quality by two reviewers.
From more than 1,600 initial citations, 10 studies met criteria for inclusion in the meta-analysis and enrolled a total of 1,339 mothers. The most frequent risk factors among participants were previous preterm birth and multiple spontaneous abortions. The high-risk mothers who received progesterone (of varying types) had significantly lower rates of preterm birth than those randomized to placebo (26.2 compared with 35.9 percent; odds ratio [OR], 0.45; number needed to treat [NNT] to prevent one premature birth = 10). Similar results were found when the most common progesterone, 17alpha-hydroxyprogesterone caproate, was considered alone (NNT = eight). There also was a lower rate of low-birth-weight infants born to mothers treated with this agent (20.3 compared with 28.4 percent; OR, 0.50; NNT = 12). Rates of perinatal mortality were lower in the treated group (14.8 compared with 17.1 percent; OR, 0.69). The incidence of respiratory distress syndrome also was lower (9.5 compared to 11.6 percent; OR, 0.83), but was not statistically significant. The rates of hospital admission for preterm labor were similar in mothers treated with progesterone and those receiving placebo.
The authors conclude that preventive therapy with progesterone reduces preterm birth in mothers at increased risk.