title: Fetal effects of anticonvulsant polytherapies: different risks from different drug combinations.
abstract: OBJECTIVE
  To determine the frequency of malformations among infants born to women who had taken lamotrigine or carbamazepine as part of polytherapy during the first trimester of pregnancy.
  
  
  METHODS
  A cohort of women enrolled during pregnancy in the North American AED (Antiepileptic Drug) Pregnancy Registry between February 1, 1997, and June 1, 2010. Information on AED use and demographic characteristics was collected in 3 telephone interviews.
  
  
  METHODS
  United States and Canada.
  
  
  METHODS
  A total of 6857 pregnant women taking an AED for any reason.
  
  
  METHODS
  Major congenital malformations were identified at birth and through the first 12 weeks after delivery. Diagnoses were based on the mother's report and confirmed by medical records. The risks of malformations were compared between polytherapy and monotherapy groups, using exact odds ratios (ORs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  The risk of malformations was 1.9% among infants exposed to lamotrigine as monotherapy (n = 1441). Among the infants exposed to lamotrigine as polytherapy (n = 505), the risks were 9.1% for lamotrigine plus valproate sodium (OR, 5.0; 95% CI, 1.5-14.0) and 2.9% for lamotrigine plus any other AEDs (1.5; 0.7-3.0). The risk of malformations was 2.9% for the infants exposed to carbamazepine monotherapy (n = 1012). For the infants exposed to carbamazepine as polytherapy (n = 365), the risks were 15.4% for carbamazepine plus valproate (OR, 6.2; 95% CI, 2.0-16.5) and 2.5% for carbamazepine plus any other AEDs (0.8; 0.3-1.9). Confounding by factors such as periconceptional vitamin use, cigarette smoking, alcohol use, and chronic maternal diseases did not explain the results.
  
  
  CONCLUSIONS
  The risk of malformations among infants exposed to lamotrigine and carbamazepine as polytherapy was higher than the corresponding monotherapies only when the polytherapy includes valproate. These findings suggest that counseling for fetal risks from AED polytherapy should be based on the specific drugs included.
authors.affiliation: North American AED Pregnancy Registry, Genetics Unit, MassGeneral Hospital for Children, Boston, MA 02114, USA. holmes.lewis@mgh.harvard.edu
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Holmes
authors.forename: Robert
authors.initials: R
authors.lastname: Mittendorf
authors.forename: Aileen
authors.initials: A
authors.lastname: Shen
authors.forename: Caitlin R
authors.initials: CR
authors.lastname: Smith
authors.forename: Sonia
authors.initials: S
authors.lastname: Hernandez-Diaz
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology* / Q000209:etiology*; D000927:Anticonvulsants / Q000009:adverse effects*; D002170:Canada / Q000453:epidemiology; D002220:Carbamazepine / Q000009:adverse effects; D015331:Cohort Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007391:International Cooperation; D000077213:Lamotrigine; D011247:Pregnancy; D011248:Pregnancy Complications; D011261:Pregnancy Trimester, First / Q000187:drug effects; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000453:epidemiology*; D011446:Prospective Studies; D012016:Reference Values; D012189:Retrospective Studies; D014227:Triazines / Q000009:adverse effects; D014481:United States / Q000453:epidemiology
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D000077213:Lamotrigine