title: Behavioural effects of fetal antidepressant exposure in a Norwegian cohort of discordant siblings.
abstract: OBJECTIVE
  Potential adverse effects of prenatal antidepressant exposure on child development are still debated. The possibility that associations are due to genetic or familial environmental risk factors rather than antidepressant use per se cannot easily be ruled out in conventional studies. Our objective was therefore to evaluate the association between prenatal antidepressant exposure and behavioural problems in a sibling controlled study.
  
  
  METHODS
  This study used data on 20 180 siblings identified from the population-based Norwegian Mother and Child Cohort Study recruited between 1999 and 2008. The mothers were asked to report antidepressant use at gestational weeks 17 and 30 and 6 months post-partum. Child Behavioral Checklist syndrome scales were used to assess externalizing and internalizing behavioural problems by questionnaires sent to mothers at 18 and 36 months postpartum. We performed unmatched and matched sibling analyses using both random- and fixed-effects linear models, respectively, to determine potential behavioural effects of antidepressant exposure.
  
  
  RESULTS
  Prenatal exposure to antidepressants was associated with increased levels of anxiety symptoms in 3 year old children after adjusting for maternal familial effects and confounding by indication (i.e. maternal depression). Effect of prenatal exposure to antidepressants was specific to anxiety, and not associated with emotional reactivity, somatic complaints, sleep problems, attention problems or aggression.
  
  
  CONCLUSIONS
  Using a sibling design, we showed that prenatal antidepressant use was specifically associated with increased anxiety symptoms after adjusting for maternal familial factors and confounding by indication.
authors: Pharmacoepidemiology and Drug Safety Research Group, School of Pharmacy, University of Oslo, Oslo, Norway, Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway, r.e.brandlistuen@farmasi.uio.no.
authors: Ragnhild Eek
authors: RE
authors: Brandlistuen
authors: Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway, Department of Psychology, Faculty of Social Sciences, University of Oslo, Oslo, Norway and.
authors: Eivind
authors: E
authors: Ystrom
authors: Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors: Malin
authors: M
authors: Eberhard-Gran
authors: Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors: Irena
authors: I
authors: Nulman
authors: Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors: Gideon
authors: G
authors: Koren
authors: Pharmacoepidemiology and Drug Safety Research Group, School of Pharmacy, University of Oslo, Oslo, Norway, Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors: Hedvig
authors: H
authors: Nordeng
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D002653:Child Behavior Disorders / Q000209:etiology*; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D015331:Cohort Studies; D003863:Depression / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D009035:Mothers / Q000523:psychology; D009664:Norway; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D012307:Risk Factors; D035781:Siblings / Q000523:psychology; D011795:Surveys and Questionnaires
chemical_list: D000928:Antidepressive Agents
keywords: Antidepressants; Norwegian Mother and Child Cohort Study (MoBa); child behaviour; depression; pregnancy; sibling design