Objective:

To assess the association between first-trimester doxycycline exposure and pregnancy loss compared with alternative antibiotics.

Approach:

• Design and data: Retrospective, active-comparator cohort study using 2005–2021 MarketScan and 1999–2019 Medicaid claims.
• Population and comparisons: Included 218,234 pregnancies among patients treated for respiratory tract infections and 6,636 among patients treated for acne. Doxycycline was compared with amoxicillin or macrolides for respiratory infections and topical clindamycin for acne.
• Methods and outcome: Pregnancies were matched by gestational age and propensity scores. The primary outcome was pregnancy loss: spontaneous abortion before 20 weeks or stillbirth at 20 weeks or later.

Key Findings:

• For respiratory tract infections, adjusted relative risk of pregnancy loss was 54% higher with doxycycline than amoxicillin in MarketScan and 40% higher in Medicaid; comparisons with macrolides showed increases of 39% and 36%, respectively.
• For acne, MarketScan showed a 49% higher adjusted relative risk with doxycycline than topical clindamycin, while Medicaid showed no statistically significant association.
• Sensitivity analyses generally supported the primary findings. Stillbirth-specific results were inconclusive because of few events.

Interpretation:

The authors reported an association between first-trimester doxycycline exposure and pregnancy loss in the respiratory-infection cohorts, while acne findings differed between databases. The observational design does not establish causation.

Limitations:

• Prescription claims did not confirm medication use, and gestational-age estimates could be inaccurate.
• Early losses without medical encounters may have been missed.
• Residual confounding, including by infection or acne severity and pregnancy intention, remained possible.
• The study did not evaluate congenital malformations.

Conclusion:

The authors stated that the findings provide additional data for evaluating doxycycline treatment and postexposure prophylaxis during pregnancy. They noted that doxycycline may remain appropriate for certain life-threatening conditions when maternal benefits outweigh potential pregnancy risks.

Sources:

• Annals of Internal Medicine