title: Neurodevelopment of children prenatally exposed to selective reuptake inhibitor antidepressants: Toronto sibling study.
abstract: BACKGROUND
  The reproductive safety of selective reuptake inhibitor (SRI) antidepressants needs to be established to provide optimal control of maternal depression while protecting the fetus.
  
  
  OBJECTIVE
  To define a child's neurodevelopment following prenatal exposure to SRIs and to account for genetic and environmental confounders in a sibling design using the Toronto Motherisk prospective database.
  
  
  METHODS
  Intelligence and behavior of siblings prenatally exposed and unexposed to SRIs were assessed by using the Wechsler Preschool and Primary Scale of Intelligence-Third Edition, Child Behavior Checklist, and Conners Parent Rating Scale-Revised and subsequently compared. Mothers, diagnosed with depression using DSM-IV, were assessed for intelligence quotient (IQ) and for severity of depressive symptoms with the Center for Epidemiologic Studies Depression scale. Prenatal drug doses and durations of exposure, child's age, child's sex, birth order, severity of maternal depression symptoms, and Full Scale IQ, the primary outcome measure, of both the mother and the child were considered in the analyses.
  
  
  RESULTS
  Forty-five sibling pairs (ages 3 years to 6 years 11 months, prenatally exposed and unexposed to SRIs) did not differ in their mean ± SD Full Scale IQs (103 ± 13 vs 106 ± 12; P = .30; 95% CI, -7.06 to 2.21) or rates of problematic behaviors. Significant predictor of children's intelligence was maternal IQ (P = .043, β = 0.306). Severity of maternal depression was a significant predictor of Child Behavior Checklist Internalizing (P = .019, β = 0.366), Externalizing (P = .003, β = 0.457), and Total scores (P = .001, β = 0.494). Drug doses and durations of exposure during pregnancy did not predict any outcomes of interest in the exposed siblings.
  
  
  CONCLUSIONS
  SRI antidepressants were not found to be neurotoxic. Maternal depression may risk the child's future psychopathology. The sibling design in behavioral teratology aids in separating the effects of maternal depression from those of SRIs, providing stronger evidence in clinical decision-making.
authors.affiliation: Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada Irena.nulman@sickkids.ca.
authors.forename: Irena
authors.initials: I
authors.lastname: Nulman
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.forename: Joanne
authors.initials: J
authors.lastname: Rovet
authors.forename: Maru
authors.initials: M
authors.lastname: Barrera
authors.forename: David L
authors.initials: DL
authors.lastname: Streiner
authors.forename: Brian M
authors.initials: BM
authors.lastname: Feldman
mesh_terms: D002648:Child; D002653:Child Behavior Disorders / Q000139:chemically induced* / Q000453:epidemiology; D002675:Child, Preschool; D003863:Depression / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007360:Intelligence / Q000187:drug effects*; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000009:adverse effects*; D009864:Ontario; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000453:epidemiology; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000453:epidemiology; D012042:Registries / Q000706:statistics & numerical data*; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: D014179:Neurotransmitter Uptake Inhibitors