Study Reassures on Azithromycin in Pregnancy and Neurodevelopmental Risks

Azithromycin exposure in pregnancy was not associated with neurodevelopmental disorders in offspring, according to a retrospective cohort study, and use in late pregnancy was linked with some lower risks.

Among over 15,000 mother-infant pairs after a mean follow-up of 5.5 years, exposure to azithromycin at any time in pregnancy was not associated with risks of any neurodevelopmental disorder compared with no exposure or exposure to other antibiotics, reported Xuerong Wen, PhD, of the University of Rhode Island in Kingston, and colleagues in JAMA Network Open.

Of note, prenatal azithromycin exposure in late pregnancy (from 20 weeks’ gestation to delivery) was associated with a lower risk of overall neurodevelopmental disorders compared with exposure to other antibiotics (adjusted HR 0.69, 95% CI 0.49-0.98), as well as a lower risk of speech and language disorder (aHR 0.59, 95% CI 0.39-0.91).

In addition, late pregnancy azithromycin exposure was associated with a lower risk of speech and language disorder compared with no antibiotic exposure during pregnancy (aHR 0.61, 95% CI 0.39-0.94).

Azithromycin’s enhanced anti-inflammatory properties may provide neuroprotective effects, particularly in late pregnancy, Wen and colleagues suggested. “Accumulating evidence indicates that neurodevelopmental outcomes may be susceptible to late pregnancy exposures.”

Wen told MedPage Today that she was “surprised” by the study’s findings, particularly given azithromycin prescription trends in pregnancy. “We’ve seen that azithromycin has been going down in use,” she noted, driven in part by fears of antibiotic resistance.

Among the study’s population, only 4.8% of mother-infant pairs were exposed to azithromycin, while 19.8% were exposed to other antibiotics and 75.4% had no antibiotic exposure.

However, “we don’t need to totally give up on this drug,” Wen said. Prescribed with caution, especially in the later stages of pregnancy, “clinicians could think about using azithromycin.”

Dani Dumitriu, MD, PhD, of Columbia University in New York City, told MedPage Today that there’s been mounting evidence that maternal inflammation during illness affects the fetus through the placenta. That makes it “incredibly important to build an empirical basis for what medications we prescribe to pregnant women,” she said.

This study’s most important finding is the lack of risk to the fetus, Dumitriu noted. Azithromycin and other antibiotics may dampen maternal inflammation and confer protection to the growing fetus. “Further strengthening this hypothesis is the fact that this protection is most observable with antibiotic use late in pregnancy, when brain development is most rapid,” she added.

For this study, the researchers used claims data from commercially insured U.S. women in the Northeast, and included 15,527 mother-infant pairs with a live birth between December 2012 and December 2023. Mothers were dispensed at least one prescription for any antibiotic or had no antibiotic exposure during pregnancy. Mean maternal age was 32.4 years.

The primary outcome was incidence of a composite of neurodevelopmental disorders, including attention deficit-hyperactivity disorder, autism spectrum disorder, speech and language disorder, developmental coordination disorder, and behavioral disorder.

Azithromycin use at any point during pregnancy was also associated with a lower risk of autism spectrum disorder compared with no antibiotic exposure (aHR 0.37, 95% CI 0.14-0.96), but Wen cautioned that the low number of autism cases meant the effect may be attributable to chance.

Study limitations included the potential for unmeasured factors to confound the results, including familial or genetic confounding. The study’s commercially insured population may affect generalizability to uninsured or publicly insured populations. In addition, the inclusion of only live births may have led to selection bias.