17-Alpha-Hydroxyprogesterone Caproate for the Prevention of Preterm Birth in Women With Prior Preterm Birth and a Short Cervical Length

The primary risk factors for recurrent spontaneous preterm birth (SPTB) are a history of SPTB and a short cervical length (CL) found on second trimester transvaginal ultrasound (TVU). In women with prior SPTB or a short CL, the most frequently used interventions to prevent preterm birth (PTB) are cerclage and progesterone supplementation. It is unclear whether the effects of the progesterone agent 17-alpha-hydroxyprogesterone caproate (17P) are additive in women with both primary risk factors. It is also unclear whether 17P is beneficial for women with a prior SPTB and a short CL not undergoing TVU-indicated cerclage. The aim of this study was to evaluate the effect of 17P for the prevention of PTB in pregnant women with prior SPTB, and a short CL, with and without TVU-indicated cerclage. The study was a secondary analysis of a randomized controlled trial sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, evaluating cerclage for singleton women with prior SPTB (17-33 6/7 weeks), and CL < 25 mm between 16 and 22 6/7 weeks. The trial was conducted by 15 US clinical centers from 2003 through 2007. The women available for the final analysis were randomized to cerclage (n = 148) or no cerclage (n = 152). The primary study outcome was the effect of 17P on PTB < 35 weeks' gestation. The cerclage and no-cerclage groups were analyzed separately. The data showed that 17P had no effect on PTB < 35 weeks in women with or without cerclage (P = 0.64; P = 0.51, respectively). The use of 17P in the no-cerclage group significantly lowered the odds of PTB < 24 weeks (odds ratio [OR], 0.08; P = 0.0022) and perinatal death (OR, 0.14; P = 0.0029). These findings suggest that the use of 17P in women with prior SPTB who underwent TVU-indicated cerclage for short CL < 25 mm provides no additive benefit for prevention of PTB < 35 weeks. In women with these primary risk factors who did not receive cerclage, 17P was associated with reduced previable birth and perinatal mortality.