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Macrolide antibiotics linked with 'small risk' of foetal neuro damage

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Macrolides antibiotics, currently considered safe during pregnancy, may carry a small risk of neurological damage and so should be reviewed by regulators, according to UK researchers. 

A third of pregnant woman in the UK are prescribed antibiotics in order to treat bacterial infections, such as cystitis and some respiratory tract infections.

“We recommend that the use of macrolides such as erythromycin during pregnancy should be reviewed”

Ruth Gilbert

The macrolide erythromycin is used to treat chlamydia and syphilis. It is also the preferred antibiotic to use in women with preterm premature rupture of membranes who are allergic to penicillin.

The researchers studied nearly 196,000 mothers who gave birth to single children born at term between 1990 and 2010, and who were prescribed antibiotics during pregnancy.

Two-thirds of the mothers prescribed antibiotics were given a type of penicillin, while 7% were prescribed macrolides.

While most recommended antibiotics were found not to harm foetuses, the researchers found an increase in the number of children who went on to develop cerebral palsy or epilepsy when mothers were prescribed macrolides instead of penicillin antibiotics. 

They highlighted that the increased risk was “still relatively small”, they noted. For every 153 women treated with a macrolide instead of a penicillin antibiotic, there would be one additional case of cerebral palsy and/or epilepsy, they said.

Writing in the online journal PLOS ONE, the researchers said: “We found no overall association between prescribing of any antibiotics during pregnancy and cerebral palsy or epilepsy in childhood.

“However, we found that prenatal prescribing of macrolides versus penicillins was associated with an increase in the relative risk of cerebral palsy or epilepsy in childhood, though the absolute risk remained low,” they added.

The authors highlighted that the finding of harm associated with macrolide use in pregnancy was consistent with findings from an earlier UK trial called Oracle Childrens Study II.

“The study is insufficient to suggest that use of macrolides in pregnancy is associated with a particular risk”

June Raine

Study co-author Professor Ruth Gilbert, from University College London’s Institute of Child Health, said: “Our study adds to evidence from several studies over the last 10 years, which have reported rare but harmful effects associated with macrolide antibiotics.

“We recommend that the use of macrolides such as erythromycin during pregnancy should be reviewed by the medicines regulator and reconsidered in national guidelines,” she said.

But Dr June Raine, MHRA director of vigilance and risk management of medicines, suggested that the regulator was unlikely to heed the researcher’s advice.

“The suggestion of a risk with the use of macrolide antibiotics during pregnancy should be treated with great caution,” she said. “The conclusion is based on small numbers and incomplete data such as information on the type and seriousness of the infection.

“[The] MHRA has sought independent expert advice, which confirms that the study is insufficient to suggest that use of macrolides in pregnancy is associated with a particular risk,” she added.

“This level of evidence does not warrant a change in current clinical guidelines”

Alan Cameron

The Royal College of Obstetricians and Gynaecologists emphasised that overall the research demonstrated no association between antibiotic prescribing to treat maternal infection with a risk of the child developing cerebral palsy or epilepsy. 

Professor Alan Cameron, the RCOG’s vice president for clinical quality, said: “The secondary analysis in this paper has shown a small increase in cerebral palsy and/or epilepsy with prenatal use of macrolides, but it does not consider the severity of the maternal infection which, in turn, has an effect on the outcome.

“This level of evidence does not warrant a change in current clinical guidelines,” he added.

The college noted that current guidelines from the National Institute for Health and Care Excellence stated that the use of prescription medicines in pregnancy should be limited and used when medically-indicated.

As reported earlier this month, US researchers have advised caution when prescribing antibiotics to women with asthma during pregnancy, as it may increase the risk of their child going on to develop the condition too.

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