Avoid prescribing macrolides to pregnant women, say UK researchers after they found the antibiotics were associated with an increased risk of significant birth defects, particularly cardiac defects.
The study is certainly going to cause some concern as to date macrolides such as erythromycin, clarithromycin and azithromycin are commonly prescribed here in Australia especially to patients who are allergic to penicillin. And given their category A pregnancy safety rating in this country, many GPs would not have thought twice about writing a script for any of these antibiotics for women who were or potentially were pregnant.
To be fair, there had been some suggestion in past that macrolides may have an effect on a baby in utero but this was generally in the realm of possible dysrhythmias and this was far from certain.
In this latest study, just published in the BMJ, researchers analysed data from those excellent UK databases. They looked at records from over 100,000 children born in the UK between 1990 and 2016, and compared outcomes of those whose mothers had been prescribed macrolides during pregnancy, those whose mothers had been prescribed penicillin during pregnancy and those prescribed neither.
The results, while not dramatic, were certainly significant.
“Macrolide prescribing during the first trimester was associated with an increased 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) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51)”, the study authors wrote.
The increased cardiovascular risks were not observed in children of mothers whose macrolides were prescribed in later pregnancy (during the second to third trimester), but this makes sense given that the first trimester corresponds to the most critical period of organogenesis.
A major concern raised by the researchers was the fact that more than one third of women who took the macrolides in pregnancy (36%), took them very early in the pregnancy – the first four weeks, often a time when they might have been unaware they were even pregnant. This suggests GPs need to exercise caution when considering giving a script for a macrolide to any woman of child-bearing age.
Interestingly, the study also found macrolide prescribing at any stage throughout the pregnancy was associated with a slightly increased risk of genital malformations (5 v 3 per 1000). But that was it as far as increased risks were concerned, despite previous suggestions that the antibiotics might have some effect on neurodevelopment.
In the end the researchers are calling for an international consensus on who should be warned and how. Currently different countries are saying different things, and even though these findings are the result of an observational study and need confirmation, they are significant enough to warrant being acted upon.
“Drug safety leaflets should report that there is uncertainty about the safety of macrolides, including erythromycin, and recommend use of alternative antibiotics when feasible until further research is available,” they concluded.
BMJ 2020;368:m331 http://dxdoi.org/10.1136/bmj.m331
This story first appeared on www.healthed.com.au