title: Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms.
abstract: Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age.
  
  
  
  This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner's Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities.
  
  
  
  Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient β = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (β = -0.18, -0.36-0.00) in females, and CAST scores in males (β = 1.91, 0.44-3.38).
  
  
  
  Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.
authors.affiliation: Center for Research in Environmental Epidemiology (CREAL).|Unitat Docent de Medicina Preventiva i Salut Publica H. Mar-UPF-ASPB.|IMIM (Hospital del Mar Medical Research Institute).|Universitat Pompeu Fabra (UPF).|Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Claudia B
authors.initials: CB
authors.lastname: Avella-Garcia
authors.affiliation: Center for Research in Environmental Epidemiology (CREAL).|IMIM (Hospital del Mar Medical Research Institute).|CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Julvez
authors.affiliation: RTI Health Solutions, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Fortuny
authors.affiliation: RTI Health Solutions, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rebordosa
authors.affiliation: Center for Research in Environmental Epidemiology (CREAL).|IMIM (Hospital del Mar Medical Research Institute).|CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: García-Esteban
authors.affiliation: Servicio de Pediatria, Hospital San Agustin, Aviles Asturias, Spain.
authors.forename: Isolina Riaño
authors.initials: IR
authors.lastname: Galán
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Public Health Department, University of Oviedo, Oviedo, Spain.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.affiliation: Environment and Health Area, CSISP-FISABIO-REDISSEC, Valencia, Spain.
authors.forename: Clara L
authors.initials: CL
authors.lastname: Rodríguez-Bernal
authors.affiliation: Environment and Health Area, CSISP-FISABIO-REDISSEC, Valencia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Iñiguez
authors.affiliation: Basic Psychological Processes and Development Department, Faculty of Psychology, University of the Basque Country, Gipuzkoa.|Health Research Institute, Biodonostia, San Sebastián, Spain.
authors.forename: Ainara
authors.initials: A
authors.lastname: Andiarena
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Health Research Institute, Biodonostia, San Sebastián, Spain.|Public Health Division of Gipuzkoa, Gipuzkoa, Basque Government, Spain.
authors.forename: Loreto
authors.initials: L
authors.lastname: Santa-Marina
authors.affiliation: Center for Research in Environmental Epidemiology (CREAL).|IMIM (Hospital del Mar Medical Research Institute).|Universitat Pompeu Fabra (UPF).|Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D001288:Attention; D000067877:Autism Spectrum Disorder / Q000139:chemically induced* / Q000453:epidemiology; D002657:Child Development; D002675:Child, Preschool; D015331:Cohort Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D015999:Multivariate Analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000453:epidemiology; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D012737:Sex Factors; D013030:Spain
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen
keywords: Acetaminophen; attention function; autism spectrum symptoms; neurodevelopment; paracetamol; pregnancy