Prenatal Antidepressant Exposure Is Associated with Risk for Autism and Attention Deficit-Hyperactivity Disorder in an Analysis of Electronic Health Records

Thursday, May 15, 2014
Atrium Ballroom (Marriott Marquis Atlanta)
C. C. Clements1,2,3, V. M. Castro2,4, S. R. Blumenthal2,3, H. R. Rosenfield2,3, S. N. Murphy5, M. Fava6, J. L. Erb7, S. E. Churchill8, A. J. Kaimal9, A. E. Doyle2,3, E. Robinson2,10, J. W. Smoller3, I. S. Kohane11 and R. H. Perlis2,3, (1)Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA, (2)Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, (3)Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, (4)Partners Research Computing, Partners HealthCare System, Boston, MA, (5)Laboratory of Computer Science and Department of Neurology, Massachusetts General Hospital, Boston, MA, (6)Depression Clinic and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, (7)Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, (8)Information Systems, Partners HealthCare System, Boston, MA, (9)Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, (10)Analytic and Translational Genomics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, (11)Department of Medicine, Brigham and Women’s Hospital, Boston, MA

The etiology of Autism Spectrum Disorders (ASD) is complex, with both environmental and genetic factors contributing to risk. Building on rodent data suggesting behavioral abnormalities in offspring with prenatal exposure to serotonergic interventions, two observational studies have suggested association between ASD and prenatal antidepressant exposure. However, questions remain about the ASD risk of maternal psychiatric morbidity, rather than antidepressant treatment per se. Given that discontinuation of antidepressant treatment during or prior to pregnancy may also be associated with substantial health risks to both the mother and child, understanding the risks of treatments is of particular significance. We hypothesized that integrating electronic health records and birth certificates would allow detailed assessment of early environmental risks for ASD.


To assess 1) the association between prenatal antidepressant exposure and ASD, 2) the influence of maternal depression, and 3) whether the risk extends to other neurodevelopmental disorders, specifically ADHD.


In the electronic health record of a large healthcare system, children who were delivered in the health system and later received a diagnosis of ASD (ICD-9 codes 299.0 Autistic Disorder, 299.8 Asperger’s Syndrome, or 299.9 PDD-NOS) were selected for inclusion. A matched healthy control cohort and a comparison cohort with a diagnosis of ADHD (ICD-9 code 314.0) were also included. Parental demographic and maternal health data were linked to child data using birth certificates and electronic health records. Data on maternal psychiatric treatment and comorbidity were included.  The association between prenatal antidepressant exposure and risk for ASD or ADHD was analyzed using logistic regression.    


Maternal and child data records were successfully linked for 775 children with ASD, 2,724 matched controls and 1,578 comparison children with ADHD.  Concordance between ICD-9 codes and diagnosis of ASD based on neuropsychological testing including ADOS administration was confirmed by manual chart review by an experienced pediatric neuropsychologist (PPV=0.73 for ASD group). Antidepressant exposure during pregnancy was associated with elevated risk for ASD (OR 1.92 [95% CI 1.31-2.78]) and for ADHD (OR 1.99 [95% CI 1.35-2.91]) in models adjusted for sociodemographic characteristics. When maternal psychiatric treatment and comorbidity and features of delivery were included in the models, the association with ASD remained significant.


Consistent with other studies, our results show that prenatal antidepressant exposure is associated with ASD risk, but suggest that this risk may not be specific to ASD. The association does not appear to be confounded by maternal treatment for depression or other psychiatric disorders and comorbidities, nor by other pre- and peri-natal variables.  However, the absolute risks are modest and should be weighed against the risks of discontinuing antidepressants. Findings also support electronic health record methodology as an efficient means of assessing pre- and peri-natal risks for ASD.

See more of: Epidemiology
See more of: Epidemiology