Doxycycline in early pregnancy linked to higher miscarriage risk
A major study of over 220,000 pregnancies finds doxycycline use in early pregnancy is associated with a 36-54% higher risk of miscarriage compared to other common antibiotics, prompting a call for caution when prescribing to women of childbearing age.
Women who took doxycycline in early pregnancy faced a significantly higher risk of pregnancy loss compared to those prescribed other antibiotics. The analysis of more than 220,000 pregnancies across commercial and Medicaid insurance databases found the increased risk persisted regardless of whether the drug was taken for a respiratory infection or for acne.
Exposure to doxycycline was associated with a 40% to 54% higher risk of miscarriage during the first trimester when compared to amoxicillin. Compared to macrolide antibiotics, the increased risk ranged from 36% to 39%. The study analyzed claims data from Merative MarketScan for commercially insured patients and from Medicaid for publicly insured patients. Pregnant women ages 12 to 55 with continuous insurance enrollment were included, with pregnancy loss defined as miscarriage or stillbirth at 20 weeks gestation or later.
Differences by Indication and Insurance Type
The increased risk was observed for both common uses of the antibiotic. Most prescriptions were for respiratory tract infections, but a significant number were for acne treatment. The association was notably stronger among privately insured women being treated for acne.
| Indication | MarketScan Participants | Medicaid Participants |
|---|---|---|
| Respiratory Tract Infection | 110,254 | 107,980 |
| Acne | 4,719 | 1,917 |
Among patients with acne, doxycycline carried a significantly higher risk of pregnancy loss than topical clindamycin for those with private insurance. This difference was not seen in the publicly insured group. Researchers noted that Medicaid patients were generally younger than those in the commercial database for both indications. The findings are clinically relevant as doxycycline is among the top four most frequently dispensed antibiotics in Australia.
Clinical Context and Limitations
Doxycycline is generally avoided in pregnancy due to known risks to fetal development. Its calcium-chelating properties may lead to discolored teeth and potential bone problems in offspring. This study, however, was limited to examining the impact on pregnancy loss and did not investigate potential effects on the fetus in full-term pregnancies. The team is now working on a separate study analyzing outcomes in live-born infants.
Many pregnancies are unplanned, leading to potential doxycycline exposure before a woman knows she is pregnant. Dr. Linda Gallo of the University of the Sunshine Coast stated the findings serve as an important warning for healthcare providers, noting the association was clear in both insurance databases. Professor Janna Morrison from the University of Adelaide highlighted the study's strength in directly comparing two common indications for the drug.
Calls for Prescribing Caution
The study authors say the results should inform treatment recommendations for infections during pregnancy. Professor Kelton Tremellen from Flinders University suggested a possible mechanism, explaining that doxycycline may interfere with biological processes essential for early placental development. This shows the need for healthcare providers to carefully weigh risks and benefits and consider alternative antibiotics for women of childbearing age.
