What is the most appropriate initial treatment for a pregnant patient with a history of two preterm deliveries presenting with vaginal spotting?

Treatment for Pregnant Patient with History of Two Preterm Deliveries Presenting with Vaginal Spotting

The answer is B - Progesterone, specifically 17-alpha-hydroxyprogesterone caproate (17-OHPC) 250 mg intramuscularly weekly, which is the recommended first-line therapy for women with a singleton pregnancy and prior spontaneous preterm birth. 1

Primary Recommendation

For women with a singleton gestation and a history of prior spontaneous preterm birth (regardless of current vaginal spotting), 17-OHPC 250 mg IM weekly starting at 16-20 weeks until 36 weeks of gestation is the standard of care. 1

• The Society for Maternal-Fetal Medicine (SMFM) explicitly recommends 17-OHPC as the preferred progestogen for this population, demonstrating a 34% reduction in recurrent preterm birth at <37 weeks (from 54.9% to 36.3%) 1, 2
• This recommendation applies to women with prior spontaneous preterm birth between 20-36 6/7 weeks, which fits this patient's history of 2 preterm deliveries 1

Why Not the Other Options

Estrogen (Option A): No evidence supports estrogen for preterm birth prevention; it is not indicated in this clinical scenario 1

Magnesium sulfate (Option C): Reserved for neuroprotection when imminent preterm delivery is expected at <32 weeks, not for prevention of preterm birth or treatment of vaginal spotting 1

Folic acid (Option D): Important for neural tube defect prevention but does not prevent preterm birth or address the current clinical presentation 1

Clinical Context: Vaginal Spotting

• The vaginal spotting requires evaluation with transvaginal ultrasound to exclude placenta previa, placental abruption, or cervical causes before any digital examination 3, 4
• However, the spotting does not change the fundamental indication for progesterone therapy based on her obstetric history 1
• If ultrasound reveals a short cervix (≤25 mm), this further strengthens the indication for progesterone therapy 1

Important Caveats

Vaginal progesterone is NOT the preferred formulation for this patient. Despite being effective for women with a short cervix and no prior preterm birth, the evidence specifically supports 17-OHPC (not vaginal progesterone) for women with prior spontaneous preterm birth 1

• A 2007 randomized trial of vaginal progesterone in women with prior preterm birth showed no benefit (PTB <32 weeks: 10.0% vs 11.3%, OR 0.9) 1
• The 2012 SMFM guideline revision specifically changed from recommending "either" formulation to preferentially recommending 17-OHPC for this population 1

Treatment should begin immediately (if between 16-20 weeks gestation) and continue weekly until 36 weeks or delivery 1, 2

Safety Profile

• The FDA-approved 17-OHPC demonstrated reductions in infant complications including intraventricular hemorrhage, necrotizing enterocolitis, and need for supplemental oxygen 2
• Long-term follow-up studies show no adverse effects on child development or physical examination 5, 2
• Common side effects include injection site pain (34.8%), swelling (17.1%), and urticaria (12.3%), but discontinuation rates are low (2.2%) 2