title: Topiramate monotherapy use in women with and without epilepsy: pregnancy and neonatal outcomes.
abstract: OBJECTIVE
  To evaluate fetal or neonatal outcomes (with a focus on major congenital anomalies) with use of topiramate monotherapy and to examine whether differences occurred in the reporting and patterns of these outcomes for pregnant women with and without epilepsy.
  
  
  METHODS
  Spontaneous, postmarketing reports involving women who used topiramate monotherapy during pregnancy from 18 July 1995 (International Birth Date of topiramate) through 30 April 2011 were retrieved from the sponsor's (Janssen Research & Development, LLC) Global Medical Safety database. All formulations for topiramate, used as monotherapy, were selected for the analysis. Monotherapy was defined as any situation where no other AED was listed in the pregnancy case report, either as a suspect or concomitant medication, regardless of indication. Results were summarized descriptively.
  
  
  RESULTS
  A total of 1163 cases of women who used topiramate monotherapy during pregnancy (for any indication) were retrieved from the Global Medical Safety database. Since some women used topiramate for more than one indication, there were a total of 1199 reported indications for topiramate monotherapy, which were primarily for treatment of epilepsy (n=599), accounting for half of the indications, and migraine prophylaxis (n=240, 20.0%). Out of 1163 cases, pregnancy outcome was reported in 50.6% (n=589). Live birth was the most frequently reported outcome, regardless of indication (epilepsy, 78.8% [312/396]; prophylaxis of migraine, 59. 3% [48/81]; other indication, 64.4% [85/132]). Cleft lip or palate anomalies (epilepsy, n=15; migraine, n=2; other indication, n=4; and indication not reported, n=2), limb, hand, or other skeletal anomalies (epilepsy, n=13; migraine, n=2; other indication, n=0; and indication not reported, n=1), and respiratory or cardiovascular anomalies (epilepsy, n=12; migraine, n=1; other indication, n=1; and indication not reported, n=2) were the most often reported major fetal or neonatal anomalies. More reported major fetal or neonatal anomalies occurred in patients being treated for epilepsy (53/79 anomaly-indication pairs) compared with patients being treated for migraine prophylaxis (10/79 anomaly-indication pairs).
  
  
  CONCLUSIONS
  Although incidence rates cannot be calculated based on spontaneous adverse event reporting, this summary of reported pregnancy and neonatal outcomes with use of topiramate monotherapy suggests that the risk for major fetal or neonatal anomalies may differ based on the indication for topiramate.
authors.affiliation: Janssen Research & Development, LLC, NJ, USA. Electronic address: rcastil4@its.jnj.com.
authors.forename: Ruby
authors.initials: R
authors.lastname: Castilla-Puentes
authors.affiliation: Janssen Research & Development, LLC, NJ, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ford
authors.affiliation: Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
authors.forename: Lewis
authors.initials: L
authors.lastname: Manera
authors.affiliation: Janssen Research & Development, LLC, NJ, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kwarta
authors.affiliation: Janssen Research & Development, LLC, NJ, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Ascher
authors.affiliation: Janssen Research & Development, LLC, NJ, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000175:diagnosis*; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D008881:Migraine Disorders / Q000188:drug therapy / Q000517:prevention & control*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose
keywords: Congenital anomalies; Postmarketing data; Pregnancy outcome; Topiramate