title: Topiramate use in pregnancy and the birth prevalence of oral clefts.
abstract: OBJECTIVE
  First marketed in the USA in 1996, topiramate (TPM) is an antiepileptic drug later approved for migraine prophylaxis, and in 2012 for weight loss in combination with phentermine. Some studies indicate an elevated prevalence of oral cleft (OC) in infants exposed to TPM in utero. We evaluated the association between TPM use in early pregnancy and the risk of OC.
  
  
  METHODS
  This retrospective cohort study used 1997-2011 automated data from four sources: HealthCore and OptumInsight (commercial insurance claims), Truven Health (Medicaid claims), and Kaiser Permanente Northern California Region (electronic medical records). We compared the prevalence of OCs in infants of women exposed to TPM in the first trimester (TPM cohort) with the prevalence in infants of women formerly exposed to TPM or other antiepileptic drugs (formerly exposed [FE] cohort) and infants of women with similar medical profiles (SMPs) to the TPM cohort that were not exposed to TPM (SMP cohort). To control for confounding, we used stratification and standardization for individual variables and propensity score deciles.
  
  
  RESULTS
  The birth prevalence of OCs was 0.36% (7/1945) in the TPM cohort, 0.14% (20/13 512) in the FE cohort, and 0.07% (9/13 614) in the SMP cohort. Standardized by site, the prevalence ratio (PR) for TPM versus FE was 2.5 (95% CI: 1.0-6.0) and for TPM versus SMP was 5.4 (95% CI: 2.0-14.6). Adjustment for covariates one at a time or by propensity score yielded similar results.
  
  
  CONCLUSIONS
  Consistent with other recent epidemiologic research, first-trimester TPM exposure was associated with an elevated birth prevalence of OC.
authors.affiliation: HealthCore, Inc., Wilmington, DE, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mines
authors.forename: Patricia
authors.initials: P
authors.lastname: Tennis
authors.forename: Suellen M
authors.initials: SM
authors.lastname: Curkendall
authors.forename: De-Kun
authors.initials: DK
authors.lastname: Li
authors.forename: Craig
authors.initials: C
authors.lastname: Peterson
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Andrews
authors.forename: Brian
authors.initials: B
authors.lastname: Calingaert
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Gaurav
authors.initials: G
authors.lastname: Deshpande
authors.forename: Daina B
authors.initials: DB
authors.lastname: Esposito
authors.forename: Nicholas
authors.initials: N
authors.lastname: Everage
authors.forename: Crystal N
authors.initials: CN
authors.lastname: Holick
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Meyer
authors.forename: Ella T
authors.initials: ET
authors.lastname: Nkhoma
authors.forename: Sherry
authors.initials: S
authors.lastname: Quinn
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rothman
authors.forename: K Arnold
authors.initials: KA
authors.lastname: Chan
mesh_terms: D002140:California / Q000453:epidemiology; D002971:Cleft Lip / Q000139:chemically induced / Q000453:epidemiology*; D002972:Cleft Palate / Q000139:chemically induced / Q000453:epidemiology*; D015331:Cohort Studies; D016208:Databases, Factual; D057286:Electronic Health Records; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology*; D015995:Prevalence; D012189:Retrospective Studies; D000077236:Topiramate
chemical_list: D000077236:Topiramate; D005632:Fructose
keywords: abnormalities; cleft lip; cleft palate; delayed effects; drug induced; oral cleft; pharmacoepidemiology; prenatal exposure; topiramate