title: Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study.
abstract: BACKGROUND
  Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking. Method Between 1999 and 2008 all pregnant Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy.
  
  
  RESULTS
  The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development [β 0.24, 95% confidence interval (CI) 0.12-0.51], communication (β 0.20, 95% CI 0.01-0.39), externalizing behaviour (β 0.28, 95% CI 0.15-0.42), internalizing behaviour (β 0.14, 95% CI 0.01-0.28), and higher activity levels (β 0.24, 95% CI 0.11-0.38). Children exposed prenatally to short-term use of paracetamol (1-27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02-0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes.
  
  
  CONCLUSIONS
  Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age.
authors.affiliation: School of Pharmacy, University of Oslo, Oslo, Norway, Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway and Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Ragnhild Eek
authors.initials: RE
authors.lastname: Brandlistuen
authors.forename: Eivind
authors.initials: E
authors.lastname: Ystrom
authors.forename: Irena
authors.initials: I
authors.lastname: Nulman
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.forename: Hedvig
authors.initials: H
authors.lastname: Nordeng
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D000374:Aggression; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D001007:Anxiety / Q000453:epidemiology; D016022:Case-Control Studies; D002657:Child Development; D002675:Child, Preschool; D015331:Cohort Studies; D003142:Communication; D003863:Depression / Q000453:epidemiology; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology*; D009048:Motor Skills; D019957:Motor Skills Disorders / Q000453:epidemiology*; D009664:Norway; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D011446:Prospective Studies; D035781:Siblings; D011795:Surveys and Questionnaires; D013694:Temperament
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen
keywords: MoBa; Norwegian Mother and Child Cohort Study; Paracetamol; acetaminophen; ibuprofen; neurodevelopment; sibling design