Hydroxyprogesterone Caproate for Preterm Birth Prevention
All women with a prior spontaneous preterm birth (20-36 6/7 weeks) in a singleton pregnancy should receive 17-alpha hydroxyprogesterone caproate (17OHP-C) 250 mg intramuscularly weekly, starting at 16-20 weeks gestation and continuing until 36 weeks or delivery. 1
Evidence for Efficacy
The recommendation is based on robust evidence demonstrating significant reductions in recurrent preterm birth and neonatal morbidity:
- 17OHP-C reduces recurrent preterm birth by 34% (from 54.9% to 36.3% at <37 weeks) in women with prior spontaneous preterm birth 1, 2
- Reductions occur across all gestational age thresholds: 33% reduction at <35 weeks and 42% reduction at <32 weeks 1, 2
- Neonatal outcomes improve significantly, with reduced rates of intraventricular hemorrhage, necrotizing enterocolitis, and need for supplemental oxygen 1, 2
Treatment Protocol
Dosing Regimen
- Dose: 250 mg intramuscularly 1
- Frequency: Weekly injections 1
- Initiation: 16-20 weeks gestation 1
- Duration: Continue until 36 weeks gestation or delivery 1
Patient Selection
- Indication: History of prior spontaneous preterm birth between 20 and 36 6/7 weeks in a singleton pregnancy 1
- Greatest benefit: Women whose earliest prior delivery occurred at <34 weeks show the most significant pregnancy prolongation with treatment 3
Critical Clinical Pitfalls
Do NOT Switch to Vaginal Progesterone
Vaginal progesterone should not be considered a substitute for 17OHP-C in women with prior spontaneous preterm birth. 1 This is a common error driven by cost or access concerns.
The evidence is clear:
- Multiple randomized trials show vaginal progesterone does not reduce recurrent preterm birth in women with prior spontaneous preterm birth 1
- The O'Brien trial (n=659) found no difference in preterm birth rates at <32 weeks (10.0% vs 11.3%) or <37 weeks (41.7% vs 40.7%) with vaginal progesterone versus placebo 1
- The OPPTIMUM study confirmed no benefit of vaginal progesterone in women with prior spontaneous preterm birth 1
Management of Cervical Shortening
If cervical shortening develops during 17OHP-C therapy, continue 17OHP-C rather than switching to vaginal progesterone (with or without cerclage placement). 1 The lack of proven benefit of vaginal progesterone in this population supports maintaining the original treatment regimen.
Predictors of Treatment Response
Approximately one-third of women will still experience recurrent preterm birth despite 17OHP-C therapy. 4 Factors associated with reduced response include:
- Earlier gestational age of previous preterm birth (each week earlier reduces odds of response) 4
- Vaginal bleeding or abruption in current pregnancy 4
- First-degree family history of spontaneous preterm birth 4
Women with these risk factors still benefit from treatment but require heightened surveillance. 4
Specific Clinical Scenarios
Women with Very Early Prior Preterm Birth
Treatment is most effective for women whose earliest prior delivery was at <34 weeks, with significant pregnancy prolongation (median 37.3 weeks with treatment vs 35.4 weeks with placebo for those with prior delivery at 20-27.9 weeks). 3
Women with Prior Late Preterm Birth (34-36.9 weeks)
While benefit is less pronounced in this subgroup, treatment should still be offered as the overall evidence supports use across the entire 20-36 6/7 week range. 1, 3
Access and Cost Barriers
Despite cost concerns, 17OHP-C remains the only FDA-approved medication for preterm birth prevention and the only progestogen with proven efficacy in this population. 5, 6 Vaginal progesterone is not an acceptable alternative based on current evidence. 1