First-trimester doxycycline exposure may be linked to higher risk of pregnancy loss

1. In this retrospective cohort study, first-trimester exposure to doxycycline, as opposed to amoxicillin or macrolides, was associated with a greater risk for pregnancy loss in pregnant patients with respiratory tract infections (RTIs).

2. Doxycycline exposure, compared with clindamycin exposure, was also associated with higher risk for pregnancy loss in pregnant patients with acne according to private insurance claims data but not according to Medicaid data.

Evidence Rating Level: 2 (Good)

Study Rundown: Doxycycline is used for a range of infections and skin conditions, making it a common medication among women of childbearing age. Although doxycycline is generally not recommended during pregnancy, it remains one of the most commonly used prescriptions among pregnant Americans. In light of shortages of penicillin G, the preferred treatment for syphilis, interest in alternative medications, including doxycycline, has increased. Using the MarketScan commercial claims and Medicaid databases, this study aimed to assess whether first-trimester exposure to doxycycline may be linked to pregnancy loss. In patients with RTIs, exposure to doxycycline was associated with a higher risk for pregnancy loss compared with exposure to amoxicillin or macrolides. In patients with acne, doxycycline exposure was associated with higher risk for pregnancy loss compared with exposure to topical clindamycin according to MarketScan data but not according to the Medicaid database. Sensitivity analyses showed consistent findings. The generalizability of this study was limited by possible residual confounding as well as possible exposure and outcome misclassification. Nevertheless, this study suggests that doxycycline use for RTI or acne may be associated with increased risk for pregnancy loss, which should be taken into account when prescribing doxycycline to women of reproductive age.

Click to read this study in the Annals of Internal Medicine

Relevant Reading: Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study

In-Depth [retrospective cohort]: This retrospective cohort study aimed to assess the effect of first-trimester doxycycline exposure on pregnancy loss. Data were obtained from MarketScan commercial claims data as well as Medicaid claims data. Pregnant women aged 12 to 55 years were included if they were continuously enrolled from 90 days prior to estimated conception to 30 days after the end of pregnancy. Pregnancies with multiple gestation, exposure to known teratogenic drugs, chromosomal anomalies, or a diagnosis of cancer were excluded. The primary outcome was pregnancy loss. The study included 4385 pregnant participants receiving doxycycline (2949 for RTI and 1436 for acne) and 220,485 who received comparator antibiotics (215,285 for RTI and 5200 for acne). Exposure to doxycycline compared with amoxicillin was associated with higher risk for pregnancy loss in patients with RTIs; the adjusted risk ratios (aRRs) were 1.54 (CI, 1.41 to 1.68) in MarketScan and 1.40 (CI, 1.28 to 1.53) in Medicaid, yielding adjusted risk differences (aRDs) of 11.07 percentage points (CI, 8.47 to 13.68 percentage points) and 7.72 percentage points (CI, 5.42 to 10.02 percentage points), respectively. Exposure to doxycycline compared with macrolides was also associated with higher risk for pregnancy loss in both MarketScan and Medicaid data. In patients with acne, exposure to doxycycline compared with topical clindamycin was linked to higher risk for pregnancy loss in MarketScan (aRR, 1.49 [CI, 1.26 to 1.76]; aRD, 8.95 percentage points [CI, 5.30 to 12.60 percentage points]) but not in Medicaid (aRR, 1.03 [CI, 0.80 to 1.33]; aRD, 0.65 percentage points [CI, -4.44 to 5.73 percentage points]). Results from sensitivity analyses were consistent with the primary analysis. Overall, this study suggested that first-trimester doxycycline exposure may be linked to higher risk of pregnancy loss.

Citation: Winterstein AG, Chen HK, Thai T, Wang Y, Smolinski NE, Wen W, et al. Doxycycline and Risk for Pregnancy Loss. ACP J Club. 2026 Nov 10. doi: 10.7326/annals-26-01647. Epub ahead of print.

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