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Research

Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study

BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3668 (Published 06 September 2017) Cite this as: BMJ 2017;358:j3668
  1. Xiaoqin Liu, postdoc1,
  2. Esben Agerbo, professor1 2 3,
  3. Katja G Ingstrup, postdoc1,
  4. Katherine Musliner, postdoc1 3,
  5. Samantha Meltzer-Brody, professor4,
  6. Veerle Bergink, associate professor1 5,
  7. Trine Munk-Olsen, associate professor1
  1. 1National Center for Register-based Research, Aarhus University, Aarhus, Denmark
  2. 2CIRRAU-Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark
  3. 3Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
  4. 4Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
  5. 5Department of Psychiatry, Erasmus Medical Centre, Rotterdam, Netherlands
  1. Correspondence to: X Liu lxq{at}econ.au.dk
  • Accepted 19 July 2017

Abstract

Objective To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders.

Design Population based cohort study.

Setting Danish national registers.

Participants 905 383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×106 person years at risk.

Exposures for observational studies Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy).

Main outcome measure First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models.

Results Overall, psychiatric disorders were diagnosed in 32 400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group.

Conclusions In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive.

Footnotes

  • Contributors: XL, EA, VB, and TMO conceived and designed the study. XL analysed the data. XL, VB, and TMO drafted the manuscript. XL, EA, KGI, KM, SMM, VB, and TMO interpreted the data and revised the manuscript critically. VB and TMO are joint last authors on this manuscript. XL is the guarantor.

  • Funding: XL, SM, and TMO are supported by the National Institute of Mental Health (NIMH) (R01MH104468). XL is also supported by the Danish Council for Independent Research (DFF-5053-00156B). SMM has received research grant support from Sage Therapeutics and Janssen to the University of North Carolina. EA, KGI, KM, and TMO are supported by iPSYCH, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (R155-2014-1724). EA is also supported by a Niels Bohr professorship grant from the Danish National Research Foundation and the Stanley Medical Research Institute. VB has received funding from the Netherlands Organization for Scientific Research (clinical fellow and VENI incentive). The investigators conducted the research independently. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support for the submitted work as described above; 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 Danish Data Protection Agency. By Danish law, no informed consent is required for a register based study using anonymised data.

  • Transparency: The lead author (the manuscript’s guarantor) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Data sharing: No additional data available.

This is an Open Access article distributed under the terms of the Creative Commons Attribution IGO License (https://creativecommons.org/licenses/by-nc/3.0/igo/), which permits use, distribution, and reproduction for non-commercial purposes in any medium, provided the original work is properly cited.

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