Researchers are warning doctors to be cautious about prescribing some antibiotics to women who are in the early stage of their pregnancy due to a possible link between the drugs and birth defects.
A study* published by The BMJ today says that children of mothers prescribed macrolide antibiotics during early pregnancy are at an increased risk of major birth defects –particularly heart defects – compared with children of mothers prescribed penicillin.
Macrolide antibiotics (including erythromycin, clarithromycin, and azithromycin) are widely used to treat common bacterial infections and are often used as alternatives for patients with penicillin allergy.
Previous studies have suggested evidence of rare but serious adverse outcomes of macrolide use, especially for unborn babies. The adverse outcomes might be associated with the pro-arrhythmic potential of macrolides and current policy advice about macrolide use in pregnancy varies.
To address these uncertainties, a team of researchers based at University College London’s Great Ormond Street Institute of Child Health set out to assess the association between macrolide antibiotics prescribed during pregnancy and major malformations as well as four neurodevelopmental disorders (cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder) in children.
The researchers analysed data from 104,605 children born in the UK from 1990 to 2016 with an average follow up of 5.8 years after birth.
Major malformations were recorded in 186 of 8,632 children whose mothers were prescribed macrolides at any point during pregnancy and 1,666 of 95,973 children whose mothers were prescribed penicillins during pregnancy.
After taking into account potentially influential factors, the researchers found macrolide prescribing during the first trimester of pregnancy meant women had a 55% higher risk of their children having a birth defect compared to women who took penicillin.
The increased risks were not observed in children of mothers whose macrolides were prescribed in later pregnancy (during the second to third trimester).
Macrolide prescribing during the first trimester was also associated with an 62% higher risk of cardiovascular malformations.
In addition, macrolide prescribing in any trimester was also associated with a 58% higher risk of genital malformations but no statistically significant associations were found for other system specific malformations or for any of the four neurodevelopmental disorders.
Given that this was an observational study, it could not establish cause and the researchers acknowledged some limitations, such as being unable to examine treatment exposure during known critical periods for specific malformations and neurodevelopmental disorders.
Nevertheless, they said that the results were largely unchanged after further analyses, suggesting that the findings withstand scrutiny.
If the associations were shown to be causal, the researchers estimated that an additional four children with cardiovascular malformations would occur for every 1,000 children exposed to macrolides instead of penicillins in the first trimester.
They concluded: “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.”
*Fan H, Gilbert R, O’Callaghan F, et al. Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study. BMJ 2020;368:m331. DOI:10.1136/bmj.m331