Workup for Multiple Preterm Births
For patients with a history of multiple preterm births, initiate 17-alpha-hydroxyprogesterone caproate (17P) 250 mg intramuscularly weekly starting at 16-20 weeks gestation and continue through 36 6/7 weeks, combined with serial transvaginal cervical length screening beginning at 16-24 weeks. 1, 2
Risk Assessment and History
The most critical element in your workup is documenting the exact gestational age and circumstances of each prior preterm birth 3:
- Distinguish spontaneous preterm labor from preterm premature rupture of membranes (PPROM) - this affects recurrence risk counseling, as PPROM carries nearly 50% recurrence risk, with 30% delivering <34 weeks, 23% <28 weeks, and 17% <24 weeks 1, 2
- Identify any history suggesting cervical insufficiency - painless cervical dilation in second trimester or unexplained second-trimester losses in absence of placental abruption 1, 2
- Document whether prior births were iatrogenic or spontaneous - only spontaneous preterm births between 20-36 6/7 weeks qualify for progesterone therapy 1
- Screen for modifiable risk factors including smoking, periodontal disease, bacterial vaginosis, and asymptomatic bacteriuria 3
Primary Prevention Strategy
17-alpha-hydroxyprogesterone caproate (17P) is the cornerstone intervention 1, 2:
- Dose: 250 mg intramuscularly weekly 1
- Timing: Start at 16-20 weeks, continue through 36 6/7 weeks 1
- This applies to all patients with prior spontaneous preterm birth 20-36 6/7 weeks, regardless of whether they had PPROM or preterm labor 2
Critical caveat: If cervical shortening develops during 17P therapy, continue 17P rather than switching to vaginal progesterone 4. Multiple randomized trials have failed to demonstrate benefit of vaginal progesterone in women with prior spontaneous preterm birth, despite its proven efficacy in women with short cervix but no prior preterm birth 4.
Cervical Length Surveillance
Begin transvaginal ultrasound cervical length measurements at 16-24 weeks gestation 1, 2:
- Perform every 2 weeks through 24 weeks 1
- Critical threshold: cervical length ≤20 mm at 24 weeks 1
- If cervix shortens to <25 mm, consider cerclage placement only if patient has classic cervical insufficiency features (painless dilation, second-trimester losses without abruption) 1, 2
Important pitfall: History-indicated cerclage should be reserved only for true cervical insufficiency, not simply for prior preterm birth 1, 2. Cerclage after previable PPROM was associated with increased odds of preterm birth (OR 14.0; 95% CI 3.97-49.35) 2.
Additional Workup Components
Screen for concurrent pregnancy complications 5:
- Gestational diabetes mellitus screening at appropriate intervals 5
- Blood pressure monitoring for hypertensive disorders 5
- Assess for signs of intrauterine infection or inflammation 6
- Evaluate for fetal growth restriction 5
Patient education on self-monitoring 2:
- Daily assessment for vaginal discharge, bleeding, contractions, and pelvic pressure 2
- Immediate reporting of any concerning symptoms 2
What NOT to Do
Avoid ineffective interventions 1:
- Do not prescribe routine bed rest or activity restriction - Grade 1B recommendation against this, as it does not improve outcomes and may increase preterm birth risk 1
- Do not use progesterone for multiple gestations - neither vaginal progesterone nor 17P are effective in twin or higher-order pregnancies 1
- Do not place cerclage based solely on prior preterm birth without classic cervical insufficiency features 1, 2
Special Considerations for Multiple Prior Preterm Births
The presence of more than one prior preterm birth is the only independent risk factor for recurrence in subsequent pregnancies 2. This patient population requires: