17-alpha Hydroxyprogesterone caproate did not reduce the rate of recurrent preterm birth in a prospective cohort study

BACKGROUND: 17-alpha Hydroxyprogesterone caproate for prevention of recurrent preterm birth is recommended for use in the United States. OBJECTIVE: We sought to assess the clinical effectiveness of 17-alpha hydroxyprogesterone caproate to prevent recurrent preterm birth <= 35 weeks compared to similar births in our obstetric population prior to the implementation of 17-alpha hydroxyprogesterone caproate. STUDY DESIGN: This was a prospective cohort study of 17-alpha hydroxyprogesterone caproate in our obstetric population. The primary outcome was the recurrence of birth <= 35 weeks for the entire study cohort compared to a historical referent rate of 16.8% of recurrent preterm birth in our population. There were 3 secondary outcomes. First, did 17-alpha hydroxyprogesterone caproate modify a woman's history of preterm birth when taking into account her prior number and sequence of preterm and term births? Second, was recurrence of preterm birth related to 17-alpha hydroxyprogesterone caproate plasma concentration? Third, was duration of pregnancy modified by 17-alpha hydroxyprogesterone caproate treatment compared to a prior preterm birth? RESULTS: From January 2012 through March 2016, 430 consecutive women with prior births <= 35 weeks were treated with 17-alpha hydroxyprogesterone caproate. Nearly two thirds of the women (N = 267) began injections <= 18 weeks and 394 (92%) received a scheduled weekly injection within 10 days of reaching 35 weeks or delivery. The overall rate of recurrent preterm birth was 25% (N = 106) for the entire cohort compared to the 16.8% expected rate (P = 1.0). The 3 secondary outcomes were also negative. First, 17-alpha hydroxyprogesterone caproate did not significantly reduce the rates of recurrence regardless of prior preterm birth number or sequence. Second, plasma concentrations of 17-alpha hydroxyprogesterone caproate were not different (P = .17 at 24 weeks; P = .38 at 32 weeks) between women delivered <= 35 weeks and those delivered later in pregnancy. Third, the mean (+/- SD) interval in weeks of recurrent preterm birth before 17-alpha hydroxyprogesterone caproate use was 0.4 +/- 5.3 weeks and the interval of recurrent preterm birth after 17-alpha hydroxyprogesterone caproate treatment was 0.1 +/- 4.7 weeks (P = .63). A side effect of weekly 17-alpha hydroxyprogesterone caproate injections was an increase in gestational diabetes. Specifically, the rate of gestational diabetes was 13.4% in 17-alpha hydroxyprogesterone caproate-treated women compared to 8% in case-matched controls (P = .001). CONCLUSION: 17-alpha Hydroxyprogesterone caproate was ineffective for prevention of recurrent preterm birth and was associated with an increased rate of gestational diabetes.