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Progesterone has been shown to reduce preterm birth in women at high risk due to short cervix (Am J Obstet Gynecol 2012 Feb;206(2):124.e1) or history of preterm birth (Cochrane Database Syst Rev 2009 Apr 15;(2):CD004947). A recent systematic review assessed the effects of prophylactic progesterone on neonatal outcomes in singleton and multiple pregnancies at risk of preterm birth. A total of 16 randomized trials were included (7 with singletons, 7 with twins, 2 with triplets) comparing systemic or vaginal progesterone vs. placebo.
In analyses including up to 2,000 singleton pregnancies, progesterone reduced the risk of neonatal death (within 28 days of birth) (risk ratio [RR] 0.49, 95% CI 0.29-0.82, NNT 32-1,000) and reduced risk of respiratory distress syndrome (RDS) (RR 0.68, 95% CI 0.49-0.94, NNT 15-83) (level 1 [likely reliable] evidence). Progesterone was also associated with reduced rates of neonatal intensive care admission (RR 0.41, 95% CI 0.2-0.82, NNT 2-15). There were no significant differences in risks of serious intraventricular hemorrhage, necrotizing enterocolitis, retinopathy, or sepsis.
For twin pregnancies, the results were very different. In analyses including up to 4,647 infants, progesterone increased the risk of both RDS (RR 1.22, 95% CI 1.04-1.43, NNH 23-125), and perinatal death (RR 1.6, 95% CI 1.01-2.4, NNH 36-1,000) (Definitions of perinatal death varied across trials but included fetal death and death within either 7 days or 28 days of birth). There was no significant difference in neonatal death following live birth, and there were no significant differences in serious intraventricular hemorrhage, necrotizing enterocolitis, retinopathy, sepsis, or neonatal intensive care unit admission. There were no significant differences in any neonatal outcomes in analysis of 2 trials with 215 triplet pregnancies (Ultrasound Obstet Gynecol 2012 Sep;40(3):257).
For more information, see the Prematurity and Prevention of preterm labor and preterm birth topics in DynaMed.