title: Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: A Danish national birth cohort study.
abstract: Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy. Previously, a positive ecological correlation between acetaminophen use and autism spectrum disorders (ASD) has been reported but evidence from larger studies based on prospective data is lacking. We followed 64,322 children and mothers enrolled in the Danish National Birth Cohort (DNBC; 1996-2002) for average 12.7 years to investigate whether acetaminophen use in pregnancy is associated with increased risk of ASD in the offspring. Information on acetaminophen use was collected prospectively from three computer-assisted telephone interviews. We used records from the Danish hospital and psychiatric registries to identify diagnoses of ASD. At the end of follow up, 1,027 (1.6%) children were diagnosed with ASD, 345 (0.5%) with infantile autism. We found that 31% of ASD (26% of infantile autism) have also been diagnosed with hyperkinetic disorders. More than 50% women reported ever using acetaminophen in pregnancy. We used Cox proportional hazards model to estimate hazard ratio (HR) and 95% confident interval (CI). Prenatal use of acetaminophen was associated with an increased risk of ASD accompanied by hyperkinetic symptoms (HR = 1.51 95% CI 1.19-1.92), but not with other ASD cases (HR = 1.06 95% CI 0.92-1.24). Longer duration of use (i.e., use for >20 weeks in gestation) increased the risk of ASD or infantile autism with hyperkinetic symptoms almost twofold. Maternal use of acetaminophen in pregnancy was associated with ASD with hyperkinetic symptoms only, suggesting acetaminophen exposure early in fetal life may specifically impact this hyperactive behavioral phenotype. Autism Res 2016, 9: 951-958. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), California. zeyanliew@ucla.edu.
authors.forename: Zeyan
authors.initials: Z
authors.lastname: Liew
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), California.|Department of Neurology, School of Medicine, UCLA, California.
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), California.
authors.forename: Jasveer
authors.initials: J
authors.lastname: Virk
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), California.|Section of Epidemiology, The Institute of Public Health, University of Aarhus, Aarhus, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity; D000067877:Autism Spectrum Disorder / Q000139:chemically induced* / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D003718:Denmark; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D013223:Statistics as Topic
chemical_list: D000082:Acetaminophen
keywords: acetaminophen; autism spectrum disorders; childhood behavior; infantile autism; pregnancy cohort; prenatal exposure