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Antidepressants during pregnancy and autism in offspring: population based cohort study

BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j2811 (Published 19 July 2017) Cite this as: BMJ 2017;358:j2811
  1. Dheeraj Rai, consultant senior lecturer in psychiatry1 2 3 4,
  2. Brian K Lee, associate professor of epidemiology and biostatistics3 5 6,
  3. Christina Dalman, professor of psychiatric epidemiology3 7,
  4. Craig Newschaffer, professor of epidemiology5 6,
  5. Glyn Lewis, professor of psychiatric epidemiology8,
  6. Cecilia Magnusson, professor of epidemiology3 7
  1. 1Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK
  2. 2Avon and Wiltshire Partnership NHS Mental Health Trust, Bristol, UK
  3. 3Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
  4. 4NIHR Biomedical Research Centre, University of Bristol, Bristol, UK
  5. 5Drexel University School of Public Health, Philadelphia, PA, USA
  6. 6AJ Drexel Autism Institute, Philadelphia, PA, USA
  7. 7Centre for Epidemiology and Community Medicine, Stockholm Health Care Services, Stockholm, Sweden
  8. 8Division of Psychiatry, University College London, London, UK
  1. Correspondence to: D Rai, Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK Dheeraj.rai{at}bristol.ac.uk
  • Accepted 31 May 2017

Abstract

Objectives To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring.

Design Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison.

Setting Stockholm County, Sweden.

Participants 254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records.

Main outcome measure Offspring diagnosis of autism spectrum disorder, with and without intellectual disability.

Results Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers’ pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability.

Conclusions The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the aetiology of autism. Importantly, the absolute risk of autism was small, and, hypothetically, if no pregnant women took antidepressants, the number of cases that could potentially be prevented would be small.

Footnotes

  • We thank Michael Lundberg, data manager at Karolinska Institutet for help with data extraction.

  • Contributors: DR and BKL are joint first authors. DR, BKL, and CM had the research idea, and CD, CN, and GL helped with its development. DR wrote the first and subsequent drafts of the paper with important intellectual input from all coauthors. BKL conducted the statistical analysis. All authors had full access to the data, specifically, the statistical reports and tables arising from the data. BKL takes responsibility of the integrity of the data and accuracy of the data analysis. All authors have approved the final version of the manuscript submitted for publication. DR, BKL, and CM are guarantors.

  • Funding: This research was funded by the Swedish Research Council (grant No 2012-3017). This research was also supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. No funder had any role in the study design; data collection, analysis, or interpretation; in the writing of the report; or in the decision to submit the article for publication. The views expressed are those of the authors and not necessarily those of the funders, the organisations they represent, the NHS, the National Institute for Health Research or the Department of Health.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form atwww.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study was approved by the research ethics committee at Karolinska Institutet, Stockholm (2013/1118-32). No individual level consent was required, and all data were anonymised before being received by the research team.

  • Data sharing: No further data available.

  • Transparency statement: The authors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; no important aspects of the study have been omitted; and any discrepancies from the study as planned have been explained.

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