title: Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system.
abstract: Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hyperactivity disorder (ADHD) delivered in a large New England health-care system were identified from electronic health records (EHR), and each diagnostic group was matched 1:3 with children without ASD or ADHD. All children were linked with maternal health data using birth certificates and EHRs to determine prenatal medication exposures. Multiple logistic regression was used to examine association between prenatal antidepressant exposures and ASD or ADHD risk. A total of 1377 children diagnosed with ASD and 2243 with ADHD were matched with healthy controls. In models adjusted for sociodemographic features, antidepressant exposure prior to and during pregnancy was associated with ASD risk, but risk associated with exposure during pregnancy was no longer significant after controlling for maternal major depression (odds ratio (OR) 1.10 (0.70-1.70)). Conversely, antidepressant exposure during but not prior to pregnancy was associated with ADHD risk, even after adjustment for maternal depression (OR 1.81 (1.22-2.70)). These results suggest that the risk of autism observed with prenatal antidepressant exposure is likely confounded by severity of maternal illness, but further indicate that such exposure may still be associated with ADHD risk. This risk, modest in absolute terms, may still be a result of residual confounding and must be balanced against the substantial consequences of untreated maternal depression.
authors.affiliation: 1] Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Clements
authors.affiliation: 1] Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA [2] Partners Research Computing, Partners HealthCare System, One Constitution Center, Boston, MA, USA [3] Laboratory of Computer Science and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Castro
authors.affiliation: 1] Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Blumenthal
authors.affiliation: 1] Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA.
authors.forename: H R
authors.initials: HR
authors.lastname: Rosenfield
authors.affiliation: 1] Partners Research Computing, Partners HealthCare System, One Constitution Center, Boston, MA, USA [2] Laboratory of Computer Science and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Murphy
authors.affiliation: Depression Clinic and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Fava
authors.affiliation: Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Erb
authors.affiliation: Information Systems, Partners HealthCare System, New Research Building, Boston, MA, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Churchill
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: 1] Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Doyle
authors.affiliation: 1] Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA [2] Analytic and Translational Genomics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Robinson
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Smoller
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, New Research Building, Boston, MA, USA.
authors.forename: I S
authors.initials: IS
authors.lastname: Kohane
authors.affiliation: 1] Center for Experimental Drugs and Diagnostics, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA [2] Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, Boston, MA, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Perlis
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology*; D000067877:Autism Spectrum Disorder / Q000453:epidemiology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004739:England; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D009034:Mother-Child Relations; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000209:etiology*; D012307:Risk Factors
chemical_list: D000928:Antidepressive Agents