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

Progesterone for Preterm Birth Prevention

For a 27-year-old pregnant woman with two previous preterm deliveries presenting with vaginal spotting, you should initiate 17-alpha-hydroxyprogesterone caproate (17OHP-C) 250 mg intramuscularly weekly, starting now (ideally between 16-20 weeks gestation) and continuing until 36 weeks or delivery. 1

Why Progesterone (17OHP-C Specifically)

The Society for Maternal-Fetal Medicine (SMFM) explicitly recommends 17OHP-C as the progestogen of choice for women with singleton pregnancy and prior spontaneous preterm birth. 1 This recommendation is based on:

• 34% reduction in recurrent preterm birth demonstrated in the landmark Meis trial (from 54.9% to 36.3% at <37 weeks) 1, 2
• Significant reductions in preterm birth at <32 and <35 weeks 1
• Decreased infant complications including intraventricular hemorrhage, necrotizing enterocolitis, and need for supplemental oxygen 1

Why NOT Vaginal Progesterone in This Patient

Vaginal progesterone should NOT be substituted for 17OHP-C in women with prior spontaneous preterm birth. 1, 2 The evidence is clear:

• Multiple RCTs (O'Brien 2007, Hassan 2011, OPPTIMUM 2016) showed no significant benefit of vaginal progesterone in women with prior preterm birth 1
• The O'Brien trial (659 women) found no difference in preterm birth rates at <32 weeks (10.0% vs 11.3%) or <37 weeks (41.7% vs 40.7%) 1
• SMFM changed its guidance in 2012 specifically because vaginal progesterone failed to demonstrate efficacy in this population 1

Vaginal progesterone is reserved for a different population: women WITHOUT prior preterm birth but WITH a sonographically short cervix (≤20 mm) detected around 24 weeks 1, 2

Why NOT the Other Options

Estrogen

• No evidence base for estrogen in preterm birth prevention
• Not mentioned in any guideline for this indication

Magnesium Sulfate

• Used for neuroprotection when preterm delivery is imminent (<32 weeks), not for prevention [@general medical knowledge]
• Not appropriate for prophylaxis in early pregnancy

Aspirin

• Used for preeclampsia prevention in high-risk women, not preterm birth prevention [@general medical knowledge]
• Different indication entirely

Practical Implementation

Dosing regimen: 1, 3

• 17OHP-C 250 mg intramuscularly weekly
• Start between 16-20 weeks gestation (start now if within this window)
• Continue until 36 weeks or delivery
• Inject in upper outer quadrant of gluteus maximus
• Slow injection (over one minute) recommended due to viscous, oily solution 3

Important Caveats

If cervical shortening develops later: 1

• Continue 17OHP-C (do NOT switch to vaginal progesterone)
• There is no evidence that changing to vaginal progesterone provides additional benefit
• Consider cerclage if cervix shortens to <25 mm, but continue 17OHP-C 1

Vaginal spotting in this context: [@general medical knowledge]

• The spotting itself doesn't change the indication for progesterone
• Evaluate for other causes of bleeding (placental issues, cervical changes)
• The history of two prior preterm births is the driving indication for 17OHP-C

Common pitfall to avoid: [1, @3