title: Exposure to antiepileptic drugs in utero and child development: a prospective population-based study.
abstract: OBJECTIVE
  Antiepileptic drugs may cause congenital malformations. Less is known about the effect on development in infancy and childhood. The aim of this study was to examine whether exposure to antiepileptic drugs during pregnancy has an effect on early child development.
  
  
  METHODS
  From mid-1999 through December 2008, children of mothers recruited at 13-17 weeks of pregnancy were studied in the ongoing prospective Norwegian Mother and Child Cohort Study. Information on birth outcomes were obtained from the Medical Birth Registry (108,264 children), and mothers reported on their child's motor development, language, social skills, and autistic traits using items from standardized screening tools at 18 months (61,351 children) and 36 months (44,147 children) of age. The relative risk of adverse outcomes in children according to maternal or paternal epilepsy with and without prenatal exposure to antiepileptic drugs was estimated as odds ratios (ORs), using logistic regression with adjustment for maternal age, parity, education, smoking, depression/anxiety, folate supplementation, and child congenital malformation or low birth weight.
  
  
  RESULTS
  A total of 333 children were exposed to antiepileptic drugs in utero. At 18 months, the exposed children had increased risk of abnormal scores for gross motor skills (7.1% vs. 2.9%; OR 2.0, 95% confidence interval [CI] 1.1-3.7) and autistic traits (3.5% vs. 0.9%; OR 2.7, CI 1.1-6.7) compared to children of parents without epilepsy. At 36 months, the exposed children had increased risk of abnormal score for gross motor skills (7.5% vs. 3.3%; OR 2.2, CI 1.1-4.2), sentence skills (11.2% vs. 4.8%; OR 2.1, CI 1.2-3.6), and autistic traits (6.0% vs. 1.5%; OR 3.4, CI 1.6-7.0). The drug-exposed children also had increased risk of congenital malformations (6.1% vs. 2.9%; OR 2.1, CI 1.4-3.4), but exclusion of congenital malformations did not affect the risk of adverse development. Children born to women with epilepsy who did not use antiepileptic drugs had no increased risks. Children of fathers with epilepsy generally scored within the normal range.
  
  
  CONCLUSIONS
  Exposure to antiepileptic drugs during pregnancy is associated with adverse development at 18 and 36 months of age, measured as low scores within key developmental domains rated by mothers. Exposures to valproate, lamotrigine, carbamazepine, or multiple antiepileptic drugs were associated with adverse outcome within different developmental domains.
authors.affiliation: Department of Clinical Medicine, Section for Neurology, University of Bergen, Bergen, Norway. gyri.veiby@hotmail.com
authors.forename: Gyri
authors.initials: G
authors.lastname: Veiby
authors.forename: Anne K
authors.initials: AK
authors.lastname: Daltveit
authors.forename: Synnve
authors.initials: S
authors.lastname: Schjølberg
authors.forename: Camilla
authors.initials: C
authors.lastname: Stoltenberg
authors.forename: Anne-Siri
authors.initials: AS
authors.lastname: Øyen
authors.forename: Stein E
authors.initials: SE
authors.lastname: Vollset
authors.forename: Bernt A
authors.initials: BA
authors.lastname: Engelsen
authors.forename: Nils E
authors.initials: NE
authors.lastname: Gilhus
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D002675:Child, Preschool; D015331:Cohort Studies; D018672:Community Health Planning; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000453:epidemiology*; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D016017:Odds Ratio; D010287:Parent-Child Relations; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000453:epidemiology*; D012042:Registries / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D012189:Retrospective Studies; D057566:Self Report; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires
chemical_list: D000927:Anticonvulsants
keywords: Epilepsy; MoBa study; Pregnancy; Teratogenicity