Antidepressant use in pregnancy does not in itself increase the risk of neurodevelopmental disorders such as autism in their offspring, a large study has found.

But women using antidepressants during pregnancy did have a higher risk of having a child with a neurodevelopmental disorder than individuals not using antidepressants, suggesting factors other than the medication may be involved.

Previous studies that have looked at this issue, most of which have focused on autism and attention deficit hyperactivity disorder (ADHD) have produced conflicting results and the issue remains controversial, the researchers reported in JAMA Internal Medicine.

A team at Harvard Medical School looked at 3.2 million pregnancies across two large health insurance databases with children followed for up to 14 years.

The crude results from 145,702 pregnancies with antidepressant exposure and more than 3 million unexposed pregnancies showed a doubling in risk of a range of neurodevelopmental outcomes.

But once the team had adjusted the analyses for an ‘extensive list’ of potential confounding factors this association began to drop away, they reported.

Overall individuals exposed to antidepressants were older and had greater medication use during pregnancy than unexposed individuals and in one of the databases, antidepressant- exposed individuals were also more likely to be white.

Careful comparisons with women who had discontinued antidepressants before pregnancy further shifted the risk towards zero and when they looked at exposed and non-exposed siblings there was no increased risk of antidepressant use.

Autism has been the most studied neurodevelopmental disorder related to antidepressants in pregnancy with some reports of 20-80% increased risk.

But after adjusting the findings for a broad range of factors, there was no association in their analysis, the researchers said.

Yet the crude association they found suggests that antidepressant use during pregnancy may be a ‘robust marker’ for neurodevelopmental risk in children and could be useful for early screening and intervention in children.

Professor Carmine Pariante, professor of biological psychiatry at the Institute of Psychiatry, Psychology and Neuroscience, King’s College London, said this was ‘truly an important paper’.

‘Women and health professionals are often concerned about antidepressants in pregnancy, and sometimes decide to suddenly stop these medications as soon as pregnancy becomes known.

‘What this study shows is that, in reality, previous concerns that antidepressant use increases the risk of autism or other neurodevelopmental disorders are due to the effects of depression itself, or to risk factors for depression, and not to antidepressants.

‘Women with clinically significant depression, or other mental disorders where antidepressants are indicated, should be informed that the risk associated with antidepressants use in pregnancy is not as high as previously thought, and should be offered the possibility to discuss this therapeutic option as part of a package of care that should include also psychological and social support.’

This comes after a study in August found that vaccination against Covid-19 in pregnancy is not linked to a higher risk of preterm birth or stillbirth. 

A version of this story was originally published on our sister publication Pulse.