Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control studyBMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f2059 (Published 19 April 2013) Cite this as: BMJ 2013;346:f2059
- Dheeraj Rai, clinical lecturer123,
- Brian K Lee, assistant professor4,
- Christina Dalman, associate professor2,
- Jean Golding, professor emeritus5,
- Glyn Lewis, professor1,
- Cecilia Magnusson, professor2
- 1Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK
- 2Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
- 3Avon and Wiltshire Partnership Mental Health NHS Trust, Bristol, UK
- 4Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, PA, USA
- 5Centre for Child and Adolescent Health, School of Social and Community Medicine, University of Bristol, UK
- Correspondence to: D Rai
- Accepted 12 March 2013
Objective To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring.
Design Population based nested case-control study.
Setting Stockholm County, Sweden, 2001-07.
Participants 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years.
Main outcome measure A diagnosis of autism spectrum disorder, with or without intellectual disability.
Exposures Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards.
Results A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.
Conclusions In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.
We thank Henrik Dal and Michael Lundberg, statisticians at the Department of Public Health Sciences, Karolinska Institutet for their contributions to data management and the coding of key variables used in this paper.
Contributors: DR, CM, and BKL had the research idea, and CD, JG, and GL helped with its development. DR conducted the analysis and wrote the first and subsequent drafts of the paper with important intellectual input from all coauthors. All authors had full access to the data, specifically, the statistical reports and tables arising from the data, and take 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 and CM act as guarantors.
Funding: This study was funded by the Swedish Research Council (grant No 2012-3017). The data linkages and staff costs have also been supported by grants from the Stockholm County Council (2007008), Swedish Council for Working Life and Social Research (2007-2064), Swedish Research Council (523-2010-1052), and Swedish Regional agreement on medical training and clinical research (ALF). 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 any of the funders or organisations they represent.
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: 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: This study was approved by the research ethics committee at Karolinska Institutet, Stockholm (DNR 2007/545-31 for main Stockholm youth cohort record linkages, and DNR 2011/1393-32 for additional linkage of maternal antidepressant use data).
Data sharing: No additional data available.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.