title: 17-alpha Hydroxyprogesterone caproate did not reduce the rate of recurrent preterm birth in a prospective cohort study.
abstract: 17-alpha Hydroxyprogesterone caproate for prevention of recurrent preterm birth is recommended for use in the United States.
  
  
  
  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.
  
  
  
  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?
  
  
  
  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).
  
  
  
  17-alpha Hydroxyprogesterone caproate was ineffective for prevention of recurrent preterm birth and was associated with an increased rate of gestational diabetes.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: DavidB.Nelson@utsouthwestern.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Nelson
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Donald D
authors.initials: DD
authors.lastname: McIntire
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: McDonald
authors.affiliation: Women and Infant Services, Parkland Health and Hospital System, Dallas, TX.
authors.forename: John
authors.initials: J
authors.lastname: Gard
authors.affiliation: Women and Infant Services, Parkland Health and Hospital System, Dallas, TX.
authors.forename: Paula
authors.initials: P
authors.lastname: Turrichi
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Leveno
mesh_terms: D000077713:17 alpha-Hydroxyprogesterone Caproate; D000328:Adult; D015331:Cohort Studies; D016640:Diabetes, Gestational / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005865:Gestational Age; D006801:Humans; D006908:Hydroxyprogesterones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D011372:Progestins; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D006908:Hydroxyprogesterones; D011372:Progestins; D000077713:17 alpha-Hydroxyprogesterone Caproate
keywords: efficacy; external validity; gestational diabetes; neonatal morbidity; prematurity; preterm birth; progesterone; progestogen; randomized trial