title: Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years.
abstract: OBJECTIVE
  Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapy may be harmful. We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities.
  
  
  OBJECTIVE
  To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years.
  
  
  METHODS
  Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery.
  
  
  METHODS
  Differential Ability Scales IQ was the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures.
  
  
  RESULTS
  In total, 42.9% of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, -0.1; 95% CI, -0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95% CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95% CI, 2-10] points higher for folate, P = .005), and breastfeeding (adjusted IQ 4 [95% CI, 0-8] points higher for breastfeeding, P = .045). For the other cognitive domains, only verbal abilities differed between the breastfed and nonbreastfed groups (adjusted verbal index 4 [95% CI, 0-7] points higher for breastfed children, P = .03).
  
  
  CONCLUSIONS
  No adverse effects of AED exposure via breast milk were observed at age 6 years, consistent with another recent study at age 3 years. In our study, breastfed children exhibited higher IQ and enhanced verbal abilities. Additional studies are needed to fully delineate the effects of all AEDs.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00021866.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, California.
authors.forename: Kimford J
authors.initials: KJ
authors.lastname: Meador
authors.affiliation: Walton Centre for Neurology and Neurosurgery, University of Liverpool, Merseyside, England.
authors.forename: Gus A
authors.initials: GA
authors.lastname: Baker
authors.affiliation: The EMMES Corporation, Rockville, Maryland.
authors.forename: Nancy
authors.initials: N
authors.lastname: Browning
authors.affiliation: Departments of Neurology, Pediatrics, and Psychiatry, Georgia Regents University, Augusta.
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Cohen
authors.affiliation: Institute of Human Development, University of Manchester, and Central Manchester University Hospitals National Health Service Foundation Trust, Manchester, England.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Bromley
authors.affiliation: Institute of Human Development, University of Manchester, and Central Manchester University Hospitals National Health Service Foundation Trust, Manchester, England.
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.affiliation: Department of Neurology, University of Southern California, Los Angeles.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Kalayjian
authors.affiliation: Department of Neurology, University of Miami, Miami, Florida.
authors.forename: Andres
authors.initials: A
authors.lastname: Kanner
authors.affiliation: Department of Neurology, Riddle Health Care, Media, Pennsylvania.
authors.forename: Joyce D
authors.initials: JD
authors.lastname: Liporace
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Page B
authors.initials: PB
authors.lastname: Pennell
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Michael
authors.initials: M
authors.lastname: Privitera
authors.affiliation: Departments of Neurology and Pediatrics, Emory University, Atlanta, Georgia.
authors.forename: David W
authors.initials: DW
authors.lastname: Loring
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D001942:Breast Feeding; D002648:Child; D003072:Cognition Disorders / Q000139:chemically induced*; D002658:Developmental Disabilities / Q000139:chemically induced*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007360:Intelligence / Q000187:drug effects*; D007361:Intelligence Tests; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D011446:Prospective Studies; D006113:United Kingdom; D014481:United States
chemical_list: D000927:Anticonvulsants