Cerebral palsy  Antibiotics in Pregnancy  Epilepsy

Antibiotic used in pregnancy linked to risk of epilepsy and cerebral palsy

Children of mothers prescribed macrolide antibiotics may be more likely to be affected by the conditions

One-third of pregnant woman in the UK are prescribed antibiotics in order to treat bacterial infections Photograph: Andrew Matthews/PA

Hannah Devlin, science correspondent

Wednesday 25 March 2015 


Scientists have raised the alert about an antibiotic routinely prescribed for chest infections, after linking it to an increased risk of epilepsy and cerebral palsy in children whose mothers took the drug during pregnancy.

Children of mothers who had taken macrolide antibiotics were found to be almost twice as likely to be affected by the conditions, prompting scientists to call for a review of their use during pregnancy. The study authors urged pregnant women not to stop taking prescribed antibiotics, however. The potential adverse effects are rare and, as yet, unproven, while infections during pregnancy are a well-established cause of health problems in babies.

Professor Ruth Gilbert, a clinical epidemiologist who led the research at Great Ormond Street Hospital in London, said: “The main message is for medicines regulators and whether they need to issue a warning about these drugs. For women, if you’ve got a bacterial infection, it’s more important to get on and treat it.”

The study tracked the children of nearly 65,000 women who had been prescribed a variety of antibiotics for illnesses during pregnancy, including chest and throat infections and cystitis. There was no evidence that most antibiotics (including penicillin, which made up 67% of prescriptions), led to an increased risk of the baby developing cerebral palsy or epilepsy.

However, when the antibiotics were compared head-to-head, the potential adverse effect of macrolide drugs emerged. Around 10 in 1,000 children whose mothers were given the drug had developed the conditions by the age of seven, compared to 6 in 1,000 children, for those who had other types of antibiotic.

The scientists could not establish whether the drugs were the cause of the increased risk, or whether there might be an alternative explanation. Macrolides can have unpleasant side-effects, including nausea, which might have made it less likely that women completed the course of drugs, meaning they were ill for longer. It is also possible that the type of infections for which macrolides are prescribed tend to be more severe of have a worse impact on the developing foetus.

Macrolides are mostly prescribed for people who are allergic to penicillin, but are also sometimes the preferred drug for respiratory infections, because they target a wider range of these infections than penicillin.

Whatever the cause, the increased risk was relatively small, according to the researchers, who estimated that for every 153 women treated with a macrolide instead of a penicillin antibiotic there would be one additional case of cerebral palsy or epilepsy.

Dr Christoph Lees, a clinical reader in obstetrics at Imperial College London, said the study raises important questions about drug safety, but added: “One thing is for sure, pregnant women should definitely take antibiotics if prescribed them as the risk of an untreated infection to the pregnancy can be catastrophic, and to put things in context the extra risk to their baby of being prescribed macrolides - if indeed there is a risk - is very tiny.”

Gilbert acknowledged that the evidence is incomplete, but urged the Medicines and Products Healthcare Regulatory Agency (MHRA) to consider issuing advice on the use of macrolides during pregnancy.

Dr June Raine, MHRA Director of Vigilance and Risk Management of Medicines, said there were no plans to review the drug, however. “The conclusion is based on small numbers and incomplete data such as information on the type and seriousness of the infection,” she said. “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.”

One-third of pregnant woman in the UK are prescribed antibiotics in order to treat bacterial infections and since infections can cross the placenta, it is important that they are treated quickly. “This is a really important message,” said Gilbert. “You’re treating two people and foetuses are much more susceptible to damage due to infection.”

The latest findings, published today in the journal PLOS One, build on a previous major trial in which around 9,000 women who had gone into labour prematurely were given macrolide antibiotics because doctors thought the drugs might help to delay childbirth. The trial found that the drug was ineffective at prolonging pregnancy, and also, unexpectedly, that children of women given the drug had higher than average rates of cerebral palsy.

Andrew Whitelaw, emeritus professor of neonatal medicine at the University of Bristol, said there was also evidence that macrolides could sometimes interfere with heart rhythms. “Were this to happen to a vulnerable foetus, it is possible that the supply of oxygen to the foetal brain could be interrupted enough to cause cerebral palsy,” he added.

“We’re seeing an accumulation of signals that together make a case for regulators to look at this issue,” said Gilbert.