Macrolide antibiotics are widely used to treat common bacterial infections – often for those with an allergy to penicillin – but experts have urged caution for their use during early pregnancy.
Nearly a third of women are prescribed antibiotics at some point in their pregnancy, with around one in 10 antibiotic prescriptions being for macrolides.
A study of 104, 605 children from University College London, which looked at data from 1990 to 2016, assessed a potential link between macrolide antibiotics and malformations at birth.
They found that, of the 8,632 children born to women who had taken macrolides during the first three months of their pregnancy, 186 had major malformations – mainly in the heart.
For women who had been given penicillin there were 1,666 out of 95,973 cases where children were born with major defects.
After accounting for other factors, the study found that there were 28 cases in 1,000 of children being born with defects to macrolide-taking mothers, compared to 18 cases per 1,000 for those who had taken penicillin.
For women who took macrolides later on in pregnancy there was no such link.
The study also looked at whether there was a link to neurodevelopmental disorders including cerebral palsy, epilepsy, ADHD and autism but they observed no such link.
Professor Ruth Gilbert, of UCL Great Ormond Street Institute of Child Health, an author on the study, said: “Our findings suggest it would be better to avoid macrolides during pregnancy if alternative antibiotics can be used.”
But she warned that women should not stop taking antibiotics when needed as “untreated infections are a greater risk to the unborn baby” and the actual risk remains low.
Andrew Shennan, Professor of Obstetrics at King’s College London, said: “These antibiotics may still be necessary to prevent serious infections, they should only be avoided if there are suitable alternatives.”
Shennan said women who want to take penicillin during pregnancy should do so as it is safe.
Professor Stephen Evans, Professor of Pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said the findings of this study should be more a message for “prescribers rather than patients”.
“It is already well-known that the prescribing of drugs, including antibiotics, should be done with caution in pregnancy,” he says. “Even if the evidence for harm of macrolides in general is not as strong as these authors suggest, there is no real evidence of absence of harm. Caution is certainly reasonable.”
Dr Sarah Stock, senior clinical lecturer in maternal and fetal medicine at the University of Edinburgh Usher Institute, said: “A study of this type can never definitively prove a drug causes birth defects, but real care is taken with the methods to ensure the findings are robust.
“The study is large and the link between macrolides and birth defects is consistent, making the finding of a small increased risk of some birth defects pretty convincing.
“Using an alternative antibiotic wherever possible in early pregnancy seems sensible. However, if macrolides are the only treatment option, women can be reassured that the absolute risk of a problem is low.”
Dr Pat O’Brien, consultant obstetrician and Vice President of the Royal College of Obstetricians and Gynaecologists agreed that although the study shows a risk, the chance overall is still very unlikely.
“It is important to realise that untreated infections during pregnancy, such as urine and chest infections, can cause harm to both mother and baby, so it’s important that they are treated appropriately,” he says.