Birth defects linked to macrolide use during pregnancy
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The use of macrolide antibiotics during pregnancy was associated with an increased risk for major malformations — particularly cardiovascular malformations — in children, according to research published in BMJ.
“Although macrolides are frequently prescribed and erythromycin specifically has been generally considered safe in pregnancy, the increased risks of major malformations found in this study suggest that there is no real evidence of an absence of harm, and macrolide prescribing during pregnancy warrants caution, including erythromycin,” Heng Fan, a PhD candidate in the population, policy and practice program in the Great Ormond Street Institute of Child Health at University College London, told Healio Primary Care.
Fan and colleagues used data from a large primary care database that represents 6.9% of the population in the United Kingdom to evaluate the association between macrolide use during pregnancy and adverse child outcomes from January 1990 to June 2016. Children included in the study were followed up to 14 years of age, death or the end of the study period. Researchers excluded children with chromosomal abnormalities as well as those born to mothers who received teratogenic drugs during pregnancy.
Fan and colleagues compared the prevalence of major malformations and neurodevelopmental disorders among children whose mothers were prescribed macrolide antibiotics — including erythromycin, clarithromycin and azithromycin — with children whose mothers were prescribed penicillin.
A total of 104,605 children who were exposed to a macrolide antibiotic or penicillin during pregnancy were included in the study.
Researchers identified major malformations in 186 of 8,632 (21.55 per 1,000) children born to mothers who took macrolides and in 1,666 of 95,973 (17.36 per 1,000) children born to mothers who took penicillin during pregnancy.
Compared with penicillin, macrolide use during the first trimester was associated with an increased risk for any major malformation (27.65 vs. 17.65 per 1,000; adjusted RR = 1.55; 95% CI, 1.19-2.03), particularly cardiovascular malformations (10.6 vs. 6.61 per 1,000; adjusted RR = 1.62; 1.05-2.51), according to Fan and colleagues.
They also identified an increased risk for genital malformations — mainly hypospadias — with macrolide use compared to penicillin use in any trimester (4.75 vs. 3.07 per 1,000; adjusted RR = 1.58; 95% CI, 1.14-2.19).
Results further showed that erythromycin use during the first trimester was associated with an increased risk for any major malformation (27.39 vs. 17.65 per 1,000; adjusted RR = 1.5; 95% CI, 1.13-1.99).
Researchers did not identify an association between macrolide use during pregnancy and neurodevelopmental disorders in children.
Because the study is observational, it cannot establish a causal relationship between macrolide antibiotic use during pregnancy and birth defects, Fan said. However, if the associations are causal, researchers estimate that for every 1,000 women who are given macrolide antibiotics instead of penicillin during the first trimester, there would be an additional 4.1 (95% CI, 0.4-9.4) children with cardiovascular malformations. They also estimate that for every 1,000 women who receive a macrolide instead of a penicillin during any trimester of pregnancy, there would be an additional 1.7 (95% CI, 0.4-3.5) children with genital malformations.
Still, Fan said that women should continue to use macrolides when there is a clinical need because the “risk of major malformations is low, and untreated bacterial infections during pregnancy are far more damaging to the unborn baby.”
“Women should not stop taking antibiotics when needed,” he continued. “But, alternatives for macrolides are recommended when feasible.” – by Erin Michael
Disclosures: The authors report no relevant financial disclosures.
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