Risk of Major Malformations Increased Among Pregnant Women Prescribed Macrolide Antibiotics

Pregnant women who are prescribed macrolide antibiotics during the first trimester are at an increased risk of any major malformations, specifically cardiovascular malformations, according to new study findings. Notably, women receiving macrolides in any trimester were at an increased risk of genital malformations. Researchers published their findings online in The BMJ.

“Macrolide antibiotics (including erythromycin, clarithromycin, and azithromycin) are among the most frequently prescribed antibiotics during pregnancy in Western countries,” study authors wrote. “Policy advice about macrolide use in pregnancy varies.” 

In order to assess the association between macrolide prescribing during pregnancy and major malformation risk in children, a team of researchers conducted a population-based cohort study. The researchers compared macrolide prescribing with penicillin prescribing. They hoped to better understand the risk of any major malformations and system specific major malformations, including nervous, cardiovascular, gastrointestinal, genital, and urinary, after macrolide or penicillin prescribing during the first trimester, second to third trimester, or any trimester of pregnancy. Further, they wanted to better understand the risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder.

The study authors observed 104,605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy—erythromycin, clarithromycin, or azithromycin—or one penicillin monotherapy from the fourth gestational week to delivery. In addition, they observed two negative control cohorts. These cohorts were comprised of 82 ,314 children whose mothers were prescribed macrolides or penicillin before conception, and 53, 735 children who were siblings of the children in the study cohort. 

“Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95,973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy,” study authors explained.  

Study findings showed that during the first trimester, macrolide prescribing increased the risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03). The findings also showed that among these major malformations, cardiovascular malformations were specifically identified (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51).

For mothers taking macrolides during any trimester, the researchers noted that their children were at an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias).  

“Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99),” they highlighted.  

The study authors noted that there were no associations found for other system specific malformations or for neurodevelopmental disorders that were statistically significant.  

“Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics,” the research team concluded. “Macrolide prescribing in any trimester was associated with an increased risk of genital malformations.”  

“These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available.” 

—Julie Gould  

Reference:

Fan H, Gilbert R, O’Callaghan F, Li L. Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study