Pregnancy duration with use of 17-α-hydroxyprogesterone caproate in a retrospective cohort at high risk of recurrent preterm birth

BACKGROUND: The use of 17-α-hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm birth has become widespread, yet there are conflicting data regarding its efficacy. OBJECTIVE: We sought to determine whether administration of 17-α-hydroxyprogesterone caproate was associated with pregnancy prolongation in women at a high risk of recurrent spontaneous preterm birth. STUDY DESIGN: This is a retrospective cohort study of women with singleton pregnancies and a history of spontaneous preterm birth at <37 weeks' gestation who received care at our academic tertiary care center between 2009 and 2019. We included women with gestations that progressed beyond 16 weeks. We excluded those who underwent history-indicated cerclage placement. We first examined the characteristics of women who received 17-α-hydroxyprogesterone caproate and those who did not. Covariates with a P value of ≤.2 on this univariate analysis were considered for incorporation into a Cox proportional hazards model to assess the association between 17-α-hydroxyprogesterone caproate use and pregnancy prolongation up to 35 weeks. RESULTS: Of 861 women included in the study, 570 (66.2%) reported non-Hispanic black racial identity, 237 (27.5%) lived in zip codes with a high infant mortality rate (≥12.1/1000 infants), 287 (33.3%) had more than 1 previous spontaneous preterm birth, 372 (43.2%) had previous spontaneous preterm birth at ≤32 weeks' gestation, and 242 (28.1%) were smokers. Here, 152 pregnancies (17.6%) were complicated by spontaneous preterm birth at <35 weeks' gestation. Factors independently associated with pregnancy duration up to 35 weeks included weight gain of <0.2 kg (0.5 lb) per week, first recorded weight of <98 kg (215 lb), obstetrical history, non-Hispanic white racial identity, lack of prenatal care, and vaginal bleeding. Gestational age at delivery was also independently associated with interventions typically employed for midtrimester cervical shortening and/or dilation, including ultrasound- and examination-indicated cerclage, pessary placement, and vaginal progesterone administration. The use of 17-α-hydroxyprogesterone caproate was not associated with pregnancy prolongation (adjusted hazard ratio, 0.83; 95% confidence interval, 0.60-1.15). CONCLUSION: The risk profile of our cohort is similar to that of women enrolled in the landmark trial that led to the Food and Drug Administration's approval of 17-α-hydroxyprogesterone caproate. Despite the high-risk nature of the pregnancies examined, we found no association between use of the medication in daily clinical practice and pregnancy prolongation up to 35 weeks. This finding adds to the mounting evidence that calls into question the drug's efficacy in reducing the risk of recurrent spontaneous preterm birth.