Do antibiotics in pregnancy cause cerebral palsy and epilepsy?

“Antibiotic used in pregnancy linked to risk of epilepsy and cerebral palsy,” The Guardian reports.

The results of a new study suggest women who take macrolide antibiotics were slightly more likely to give birth to a child with one (or both) of these conditions, compared with women who take penicillin.

But no association was found between taking antibiotics in general during pregnancy and cerebral palsy (a condition that causes movement disorders) or epilepsy (a condition that causes seizures).

However, a direct comparison between these groups of women is not entirely reliable. There could be other confounding factors that could account for the difference seen, such as the type and severity of infection.

The study does not prove that macrolides cause either cerebral palsy or epilepsy. It is possible an underlying infection in pregnancy increased the risk of these conditions, rather than the treatment itself.

There is no such thing as an entirely 100% risk-free medical intervention. This means we need to use the best evidence available to make an informed decision about the trade-off between the benefits and risks of various choices.

Most experts would agree that the benefits of treating bacterial infections in pregnancy far outweigh the potential risks of antibiotics – if infections are left untreated, it could result in the infection being passed on to the baby, or most seriously, miscarriage or stillbirth.

Where did the story come from?

The study was carried out by researchers from University College London and the Farr Institute of Health Informatics Research, London, and was funded by the Medical Research Council.

It was published in the peer-reviewed journal PLOS One on an open-access basis, so it is free to read online.

The Guardian, The Daily Telegraph and the Mail Online’s reporting was accurate and responsible. All three papers pointed out that the increased risk from macrolides found in the study was small and could be explained by other factors (confounders).

The papers also included advice from experts that women should continue to take antibiotics prescribed for infection.

It is a shame, then, that all three papers chose to run with alarmist headlines that failed to put the increase in risk into any useful context.

The papers also singled out a common antibiotic called erythromycin. This belongs to the group called macrolides, but it was not focused on by the study.

What kind of research was this?

This was a retrospective cohort study involving 195,909 women. It looked at whether antibiotics prescribed during pregnancy were linked to a higher risk of cerebral palsy or epilepsy in their children.

Cohort studies are often used to look at whether particular events are linked to certain health outcomes. The advantage with this type of study is that it can follow large groups of people over long periods of time, but they cannot prove cause and effect.

Retrospective cohort studies, which look back over time, may also be less reliable than those that follow people in time, called prospective cohort studies.

The authors say antibiotics are one of the most frequently prescribed drugs during pregnancy.

However, they say one large randomised controlled trial (RCT) found certain antibiotics given to women who had gone into premature labour were associated with an increased risk of cerebral palsy or epilepsy in their children at seven years of age.

The two antibiotics used in this previous trial were erythromycin, a macrolide, and co-amoxiclav, which is a type of penicillin.

What did the research involve?

The researchers used data on 195,909 women who had registered at their GP surgeries before pregnancy and had a baby born at or after term (37 weeks).

For women with multiple pregnancies (about one-quarter of the cohort), one pregnancy was selected randomly for analysis. Women whose children were born preterm were excluded because premature babies already have an increased risk of cerebral palsy and epilepsy.

They looked at whether the women had been treated with any oral antibiotics during pregnancy, and, if so, which class of antibiotics, the number of courses they had, and the timing of treatment during pregnancy.

The women’s children were followed until seven years of age for any diagnosis of cerebral palsy or epilepsy, as recorded in the children’s primary care records.

The researchers analysed the data using standard statistical methods. They adjusted their results for a wide range of maternal risk factors.

These included maternal age at delivery; pregnancy complications; chronic conditions such as obesity; treatment for chronic medical conditions during pregnancy; tobacco and alcohol use; social deprivation; and maternal infections that could potentially cause damage to the foetal brain.

What were the basic results?

A total of 64,623 (33.0%) of the women were prescribed antibiotics in pregnancy, and 1,170 (0.60%) children had records indicating they had cerebral palsy or epilepsy, or both.

Once the researchers adjusted their results for confounders, they found:

• no association between antibiotics and cerebral palsy or epilepsy (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.91-1.19)
• compared with penicillins, macrolide antibiotics were associated with a 78% increased risk of cerebral palsy or epilepsy (HR 1.78, 95% CI 1.18-2.69; number needed to harm 153, 95% CI 71-671)
• children whose mothers received more than three antibiotic prescriptions during pregnancy had a 40% increased risk (HR 1.40; 95% CI 1.07-1.83) compared with those with no prescriptions

How did the researchers interpret the results?

The researchers say that their findings indicate the prescribing of macrolides in pregnancy is linked to an increased risk of cerebral palsy or epilepsy in childhood.

They speculated about why macrolides might be associated with harm – arguing, for example, that if women stopped taking the drugs because of side effects, the partially treated infection might prolong the foetal brain’s exposure to inflammation.

However, they add that there is growing evidence that taking macrolides during pregnancy is associated with harm, and these drugs may have specific adverse effects on the foetus.

Conclusion

The findings from this large study indicate that antibiotic use in pregnancy was not associated with an increased risk of cerebral palsy or epilepsy. The apparent increased risk of macrolides compared with penicillin is not reliable.

A direct comparison between the women taking each type of antibiotic is inaccurate, as it does not take into account potential confounding factors. These include:

• the type and severity of the infections, which could have affected the baby, rather than the antibiotic
• whether the women took all of the course of antibiotic or not as a result of side effects; if stopped early, the infection may not have been fully cleared and could have then harmed the baby
• other unmeasured maternal factors that influenced the type of antibiotic the women were given, such as other medications or health conditions

Additionally, the analysis for macrolides was based on small numbers of women, so the results could also have occurred by chance. It is important to stress that the risk to individual pregnancies is small.

Doctors will only prescribe antibiotics in pregnancy if they think there is a clear clinical need, where mother and baby are potentially at threat. Any risk to your pregnancy posed by antibiotics will probably be far outweighed by the benefits of treatment.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.