Prenatal Azithromycin Exposure and Risk of Neurodevelopmental Disorders in Children

Importance: Azithromycin is commonly used during pregnancy to treat bacterial infections, but its effects on neurodevelopmental disorders (NDDs) remain inconclusive. Objective: To evaluate the risk of NDDs in children prenatally exposed to azithromycin compared with those exposed to other antibiotics or with no antibiotic exposure during gestation. Design, Setting, and Participants: This retrospective cohort study used data from an administrative health claims database (January 1, 2012, to October 31, 2024). The study evaluated a mother-infant cohort of mothers aged 12 to 55 years with a live birth between December 1, 2012, and December 31, 2023, who filled at least 1 prescription for an antibiotic or were unexposed to antibiotics during pregnancy. Mothers with antibiotic exposure within 90 days before pregnancy were excluded. Exposures: Propensity scores were used to match children exposed to azithromycin with those exposed to other antibiotics or no antibiotics during the entire, early, and late pregnancy periods. Main Outcomes and Measures: Cox proportional hazards regression models were applied to assess the incidence of NDDs, including attention-deficit/hyperactivity disorder, autism spectrum disorder, speech and language disorder (SLD), developmental coordination disorder, and behavioral disorders, during follow-up, in the azithromycin cohort compared with those exposed to other antibiotic classes or those with no antibiotic exposure. Results: Among 15 527 mother-infant dyads (mean [SD] maternal age, 32.4 [4.1] years) included in this study, 742 (4.8%) were exposed to azithromycin, 3079 (19.8%) were exposed to other antibiotics, and 11 706 (75.4%) remained unexposed to antibiotics during pregnancy. After a mean (SD) follow-up of 5.5 (3.0) years, late pregnancy azithromycin exposure was associated with a lower risk of SLD compared with those unexposed (adjusted hazard ratio [AHR], 0.61; 95% CI, 0.39-0.94) as well as a lower risk of overall NDDs (AHR, 0.69; 95% CI, 0.49-0.98) and SLD (AHR, 0.59; 95% CI, 0.39-0.91) compared with those exposed to other antibiotics. Conclusions and Relevance: In this cohort study, late pregnancy azithromycin exposure was associated with a lower risk of NDDs, particularly SLDs. However, azithromycin prescribing during pregnancy should remain guided by clinical necessity and existing safety recommendations; further studies using larger and more diverse populations are warranted to confirm these findings.