Doxycycline and Risk for Pregnancy Loss : A Multi-database, Multi-indication Cohort Study
Related Experiment Videos
Almut G Winterstein1, Hung-Kai Chen2, Thuy Thai3
1Department of Pharmaceutical Outcomes and Policy, Department of Epidemiology, and Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida (A.G.W.).
Background:
Doxycycline is commonly prescribed to reproductive-aged women, but evidence about safety during pregnancy is limited.
Objective:
To evaluate the risk for pregnancy loss after doxycycline exposure in the first trimester.
Design:
Retrospective active-comparator cohort study.
Setting:
Merative MarketScan commercial (2005-2021) and Medicaid (1999-2019) claims data.
Participants:
Pregnancies ending in loss or live birth among women aged 12 to 55 years.
Intervention:
3 cohorts of pregnancies with first-trimester oral doxycycline or comparator antibiotic prescription fills and concomitant diagnoses of respiratory tract infection (RTI) or acne.
Measurements:
Pregnancy loss was evaluated using validated algorithms. Doxycycline-exposed pregnancies were matched on propensity score and gestational age to comparator pregnancies (exposed to amoxicillin or a macrolide for RTI or topical clindamycin for acne). Adjusted risk differences and adjusted risk ratios (aRRs) were estimated via binomial and modified Poisson regression separately for each database and comparison.
Results:
The study included 218 234 pregnant participants with RTI (110 254 in MarketScan, 107 980 in Medicaid) and 6636 with acne (4719 in MarketScan, 1917 in Medicaid). Among those with RTI, doxycycline use was associated with an increased risk for pregnancy loss compared with amoxicillin use (MarketScan aRR, 1.54 [95% CI, 1.41 to 1.68]; Medicaid aRR, 1.40 [CI, 1.28 to 1.53]). Results were similar for the comparison with macrolides (MarketScan aRR, 1.39 [CI, 1.28 to 1.51]; Medicaid aRR, 1.36 [CI, 1.25 to 1.48]). Among patients with acne, the comparison with topical clindamycin was statistically significant in MarketScan (aRR, 1.49 [CI, 1.26 to 1.76]) but not Medicaid (aRR, 1.03 [CI, 0.80 to 1.33]). Among cohorts with statistically significant aRRs, risk differences ranged between 7 and 11 percentage points.
Limitation:
Residual confounding and exposure or outcome misclassification are possible, and congenital malformations were not evaluated.
Conclusion:
Doxycycline use for RTI or acne during early pregnancy was associated with an increased risk for pregnancy loss. Clinicians may use this information to weigh risks and benefits when prescribing doxycycline to reproductive-aged women.
Primary Funding Source:
Centers for Disease Control and Prevention.
Related Concept Videos
01:07Teratogenicity
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
01:11Bioavailability Study Design: Single Versus Multiple Dose Studies
01:24Drug Toxicity: Risk factors