doxycycline and risk of pregnancy loss

• a large retrospective active-comparator cohort study evaluated the risk of pregnancy loss following first-trimester oral doxycycline exposure in women aged 12 to 55 years
• study design and population: analysed US commercial (Merative MarketScan, 2005–2021) and public (Medicaid, 1999–2019) claims databases across three indication-matched cohorts:
  • 218,234 pregnancies with respiratory tract infection (RTI) (110,254 in MarketScan and 107,980 in Medicaid) comparing oral doxycycline against oral amoxicillin or a macrolide
  • 6,636 pregnancies with acne (4,719 in MarketScan and 1,917 in Medicaid) comparing oral doxycycline against topical clindamycin
  • pregnancies were matched on propensity score and gestational age, and pregnancy loss was identified using validated claims algorithms

Key findings

• respiratory tract infection (RTI) cohorts: first-trimester oral doxycycline exposure was consistently associated with a statistically significant increased risk of pregnancy loss compared with active comparators:
  • vs amoxicillin: adjusted risk ratio (aRR) 1.54 (95% CI 1.41 to 1.68) in MarketScan and aRR 1.40 (95% CI 1.28 to 1.53) in Medicaid
  • vs macrolides: aRR 1.39 (95% CI 1.28 to 1.51) in MarketScan and aRR 1.36 (95% CI 1.25 to 1.48) in Medicaid
• acne cohorts: first-trimester oral doxycycline compared with topical clindamycin showed a statistically significant increased risk of pregnancy loss in the commercial database (MarketScan aRR 1.49, 95% CI 1.26 to 1.76), whereas no statistically significant association was observed in the Medicaid cohort (aRR 1.03, 95% CI 0.80 to 1.33)
• absolute risk difference: across cohorts demonstrating statistically significant relative increases, absolute risk differences for pregnancy loss ranged between 7 and 11 percentage points

Study limitations and clinical implications

• methodological limitations: as an observational claims-based study, residual confounding and exposure or outcome misclassification remain possible; additionally, congenital malformations were not evaluated
• clinical practice considerations: although tetracyclines are generally contraindicated in pregnancy, inadvertent first-trimester exposure frequently occurs before pregnancy is recognised; clinicians should carefully weigh risks and benefits and consider pregnancy testing or alternative agents (such as penicillins or macrolides where clinically appropriate) when prescribing doxycycline to women of reproductive potential

Reference:

1. Winterstein AG, Chen HK, Thai T, et al. Doxycycline and Risk for Pregnancy Loss: A Multi-database, Multi-indication Cohort Study. Ann Intern Med. 2026 Nov 10. doi: 10.7326/ANNALS-26-01647.