By Lisa Rapaport

(Reuters Health) – Pregnant women have another reason to avoid taking a class of antibiotics that includes erythromycin, clarithromycin and azithromycin: it may increase their baby’s risk of birth defects, a UK study suggests.

Compared to women prescribed penicillin during their first trimester, mothers given antibiotics in the macrolide class – which has already been tied to miscarriages – were 55% more likely to have a baby with major birth defects, the study found.

“Macrolides are frequently prescribed in pregnancy, and our findings suggest it would be better to avoid macrolides during pregnancy if alternative antibiotics can be used,” said study leader Heng Fan of University College London.

Many pregnant women who are allergic to penicillin are prescribed macrolides for bacterial infections, researchers note in The BMJ.

Fan’s team examined data on 104,605 children born from 1990 to 2016 whose mothers were prescribed penicillin or macrolides during pregnancy.

Overall, 186 children born to mothers prescribed macrolides at any point in pregnancy had major birth defects, including malformations of the brain and nervous system, heart and lungs, digestive tract, genitals or urinary tract. That translates into a birth defect rate of 28 out of every 1,000 babies.

Most women in the study were prescribed penicillin. Among these mothers, 1,666 children had major birth defects, or 18 per 1,000 babies.

Macrolides taken during the first trimester were tied to a higher risk of cardiovascular malformations, with a birth defect rate of 11 out of 1,000 babies, compared with 7 in 1,000 babies for penicillin.

Use of erythromycin during the first trimester was linked to a 27 per 1,000 rate of major malformations, versus 18 per 1,000 with penicillin.

Macrolide use during any trimester was also linked to a genital malformations rate of 5 per 1,000 versus 3 per 1,000 with penicillin.

Although the risk of major birth defects is higher with macrolides, the risk is still quite low and should be balanced against the even more serious problems that can develop for babies whose mothers have untreated bacterial infections during pregnancy, Fan said by email.

Uterine infections – one use for antibiotics during pregnancy – can damage the placenta, contribute to premature labor and also lead to birth defects, for example. These infections can also make labor more difficult and dangerous for mothers and babies.

Rather than avoid antibiotics, pregnant women should use penicillin unless they have a confirmed allergy, Fan said. Macrolides should be used with caution, and only when penicillin isn’t an option.

Along with to birth defects, researchers also looked for connections between antibiotics and cerebral palsy, epilepsy, attention deficit hyperactivity disorder (ADHD) and autism but found no links.

The study wasn’t designed to prove whether or how certain antibiotics might directly cause birth defects.

Still, it adds to evidence suggesting that macrolides should be avoided as much as possible during pregnancy, said Anick Berard of CHU Sainte-Justine and the University of Montreal.

“Given that infections need to be treated during pregnancy, I suggest less-problematic antibiotics use like penicillin or amoxicillin,” Berard, who wasn’t involved in the study, said by email. “These molecules are safe.”

This may be easier said than done if more bacteria develop that are resistant to treatment with penicillin, Berard noted.

SOURCE: The BMJ, online February 19, 2020.