Exposure to macrolide antibiotics in utero was not found to increase the risk for major birth defects in offspring, according to results from a nationwide cohort study published in The British Medical Journal.

Data from pregnancies (N=1,192,539) occurring between 1997 and 2016 were analyzed for this study. The investigators assessed whether the use of antibiotics during pregnancy was associated with birth defects diagnosed within the first year of life. A major study outcome was major birth defects diagnosed during inpatient or outpatient care.

A total of 13,019 pregnancies had macrolide antibiotic exposure. More than 40,345 pregnancies had recent exposure to macrolide antibiotics, 51,515 had exposure to penicillin, and 995,673 had no antibiotic exposures.


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Among the group exposed to macrolide antibiotics, 41.9% used erythromycin, 36.2% used azithromycin, 18.2% used roxithromycin, and 3.6% used clarithromycin. The median time from start of pregnancy to macrolide antibiotic exposure was 28 days.

Propensity-matched cohorts comprised macrolide antibiotic and penicillin exposure pregnancies (1:1 ratio; n=26,034), macrolide antibiotic exposure and macrolide recent use (1:1 ratio; n=23,826), and macrolide antibiotic exposure and no antibiotic use (1:4 ratio; n=65,094).

In total, 457 infants exposed to macrolide antibiotics in utero were diagnosed with a major birth defect. Comparatively, 481 infants exposed to penicillin (relative risk [RR], 0.95; 95% CI, 0.84-1.08), 434 infants with recent macrolide antibiotic exposure (RR, 1.00; 95% CI, 0.88-1.14), and 1738 infants with no antibiotic exposure (RR, 1.05; 95% CI, 0.95-1.17) were diagnosed with a major birth defect.

Compared with penicillin, the use of azithromycin (RR, 1.04; 95% CI, 0.86-1.27), erythromycin (RR, 0.82; 95% CI, 0.67-1.01), and roxithromycin (RR, 1.10; 95% CI, 0.82-1.49) was not associated with increased risk for major birth defects.

Stratified by trimester of antibiotic exposure, the risk for major birth defects did not increase during the second and third trimesters (RR, 1.02; 95%, 0.93-1.12). The specific risk for heart defects did not vary between macrolide antibiotic and penicillin exposures (RR, 0.98; 95% CI, 0.77-1.26).

This study may have been limited by lack of access to information about maternal alcohol consumption, fever, or folic acid supplementation.

These data indicate that the risk for major birth defects in offspring was not found to be increased among pregnant women exposed to macrolide antibiotics compared with penicillin exposure or no antibiotic exposure during pregnancy.

Reference

Andersson NW, Olsen RH, Andersen JT. Association between use of macrolides in pregnancy and risk of major birth defects: nationwide, register based cohort study. BMJ. Published online February 10, 2021. doi:10.1136/bmj.n107