title: Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study.
abstract: Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50-1.54 for ASD; 0.97, 95% confidence interval 0.53-1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.
authors.affiliation: Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA.|Partners Research Computing, Partners HealthCare System, One Constitution Center, Boston, MA, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Castro
authors.affiliation: Informatics Program, Boston Children's Hospital, Boston, MA, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Kong
authors.affiliation: Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA.|Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Clements
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Brady
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Kaimal
authors.affiliation: Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA.|Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Doyle
authors.affiliation: Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA.|Analytic and Translational Genomics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Robinson
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Churchill
authors.affiliation: Informatics Program, Boston Children's Hospital, Boston, MA, USA.|Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.|Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: I S
authors.initials: IS
authors.lastname: Kohane
authors.affiliation: Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA.|Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Perlis
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology*; D001321:Autistic Disorder / Q000453:epidemiology*; D015984:Causality; D002648:Child; D002675:Child, Preschool; D003866:Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents