Preterm birth is the leading cause of neonatal morbidity and mortality in the United States and is one of the leading causes worldwide, with the highest rates of mortality occurring in those born at less than 32 weeks’ gestation. A history of preterm birth is one of the strongest risk factors for recurrent preterm delivery; however, early cervical shortening and multiple gestations also confer an increased risk of preterm birth. The precise causal mechanisms underlying the preterm birth pathway are still under investigation; however, available evidence suggests a role of progesterone in preterm birth prevention in certain high-risk populations. Specifically, intramuscular 17-hydroxyprogesterone appears beneficial in women with a prior preterm birth at less than 37 weeks’ gestation (relative risk, 0.55; 95% confidence interval, 0.42–74) and preterm birth at less than 34 weeks’ gestation (relative risk, 0.31; 95% confidence interval, 0.14–0.69). Vaginal progesterone has been found to reduce preterm birth in women with a foreshortened cervix as measured by transvaginal ultrasonography. There is unfortunately no evidence whatsoever that progesterone reduces preterm birth among women with multiple gestations. Additional research into the mechanisms of preterm birth and the potential for progesterone and other preventive interventions is necessary.

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