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A retrospective study of 218,234 pregnancies found that doxycycline use in early pregnancy was associated with higher pregnancy-loss risk than some other antibiotics for respiratory infections. Results for acne differed by insurance group, and the study cannot establish that doxycycline caused the losses or assess congenital malformations.
A study of 218,234 pregnancies found that exposure to the antibiotic doxycycline during early pregnancy was associated with a higher risk of pregnancy loss than use of certain alternative antibiotics. The findings, published in Annals of Internal Medicine, compare treatments for respiratory infections and acne but do not show that doxycycline caused the losses.
For respiratory tract infections, doxycycline was associated with higher pregnancy-loss risk than amoxicillin in both insurance datasets. The adjusted risk ratio was 1.40 in Medicaid claims (95% confidence interval 1.28–1.53) and 1.54 in commercially insured patients (1.41–1.68). The researchers also reported higher risk compared with macrolide antibiotics: adjusted risk ratios were 1.36 in Medicaid and 1.39 in MarketScan.
Among patients treated for acne, the comparison with topical clindamycin showed a different pattern. The risk was higher in the commercially insured group, with an adjusted risk ratio of 1.49 (1.26–1.76), but researchers did not find a statistically significant increase in the Medicaid group: 1.03 (0.80–1.33). These are comparisons between treatment groups, not estimates of an individual patient’s absolute chance of pregnancy loss.
The team, led by Almut Winterstein of the University of Florida, used insurance claims from MarketScan for 2005–2021 and Medicaid for 1999–2019. Participants were matched to similar pregnancies involving comparator antibiotics. The primary outcome combined miscarriage and stillbirth at 20 weeks or later. Doxycycline exposure was assessed from conception through the end of the first trimester, approximately 76 days.
Choosing Antibiotics in Early Pregnancy
The findings may inform decisions when an antibiotic is being considered for someone who is pregnant or could be pregnant but does not yet know it. Doxycycline is prescribed for conditions including respiratory infections and acne, and the study suggests that its pregnancy-loss association should be weighed against alternatives for those indications.
The results do not mean that patients should stop or change a prescribed medicine without speaking with a qualified clinician. The study is observational, and its comparisons cannot establish cause and effect. Treatment choices depend on the infection or condition, the patient’s circumstances, and the available alternatives.
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How the Study Compared Treatments
Doxycycline is generally not recommended during pregnancy. Winterstein noted that the drug’s calcium-chelating properties may affect developing teeth and bones; the study itself did not evaluate congenital malformations or other fetal outcomes. The report says women of childbearing age may nonetheless receive doxycycline, including before they realize they are pregnant.
This was a retrospective, active-comparator study based on claims rather than a randomized trial. Most participants received antibiotics for respiratory tract infections: 110,254 in MarketScan and 107,980 in Medicaid. Smaller groups received treatment for acne, numbering 4,719 and 1,917, respectively. Medicaid participants tended to be younger than those in the commercial insurance dataset.
“Clinicians, together with their patients, might want to weigh the benefits against the potential risk for pregnancy loss when considering doxycycline for reproductive-aged women.”
— Almut Winterstein and colleagues, study authors
Limits of the Pregnancy-Loss Evidence
The study found an association, but residual confounding could affect the results: claims data may not capture all differences between people prescribed doxycycline and those given comparison drugs. The researchers also cited possible exposure or outcome misclassification. The study cannot establish whether doxycycline itself contributed to pregnancy loss.
It did not assess congenital malformations or broader outcomes among fetuses and infants. The acne findings also differed between commercial and public insurance datasets, and the reasons for that difference are not established in the reported results. The study reports relative comparisons; it does not provide an absolute risk estimate for an individual patient.
Further Infant Outcomes Under Study
Winterstein said the research team is working on a separate study examining outcomes in live-born infants. That analysis may address questions not answered by the pregnancy-loss study, although its timing and specific findings were not provided in the report.
For now, the reported evidence supports a discussion between patients and clinicians about treatment options when doxycycline is being considered around early pregnancy. The current study does not establish a change in prescribing guidance, and additional research will be needed to clarify the association and assess outcomes beyond pregnancy loss.
Key Questions
Does the study prove doxycycline causes pregnancy loss?
No. It was an observational analysis of insurance claims and found an association. The authors noted possible confounding and misclassification, so the study cannot establish cause and effect.
What pregnancy stage did the researchers examine?
The study assessed antibiotic exposure from conception through the end of the first trimester, approximately 76 days.
Were all comparisons consistent across insurance groups?
No. For respiratory infections, higher relative risk compared with amoxicillin was reported in both datasets. For acne, the comparison with topical clindamycin showed a statistically significant increase in the commercially insured group but not in the Medicaid group.
Did the study examine birth defects or infant health?
No. The analysis focused on pregnancy loss, defined to include miscarriage and stillbirth at 20 weeks or later. The report says congenital malformations were not evaluated; the research team is studying outcomes in live-born infants separately.
Source: medpagetoday.com
