First trimester exposure to topiramate and the risk of oral clefts in the offspring: A systematic review and meta-analysis

Reprod Toxicol. 2015 Jun:53:45-50. doi: 10.1016/j.reprotox.2015.03.003. Epub 2015 Mar 20.

Abstract

Topiramate (TPM) is an increasingly used drug during childbearing ages for treatment of epilepsy, migraine, and appetite suppression as well as for off-label indications such as sleep and psychiatric disorders. Presently, while some reports suggested an increased risk of oral cleft (OC), these reports are balanced by studies that could not confirm such association. We conducted a meta-analysis of all studies reporting on women exposed to TPM during pregnancy. Of the 2327 publications reviewed, 6 articles met the inclusion criteria including 3420 patients and 1,204,981 controls. The odd ratio (OR) of OC after the first trimester exposure to TPM exposure was 6.26 (95% confidence interval: 3.13-12.51; P = 0.00001). This study provides strong evidence that TPM is associated with an increased risk of OC in infants exposed to TPM during embryogenesis and should lead to a careful review of TPM use in women of reproductive ages.

Keywords: Epilepsy; Infants; Oral cleft; Pregnancy; Teratogenicity; Topamax; Topiramate.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-Obesity Agents / adverse effects*
  • Anticonvulsants / adverse effects*
  • Cleft Palate / chemically induced*
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Humans
  • Pregnancy
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects*
  • Risk
  • Topiramate

Substances

  • Anti-Obesity Agents
  • Anticonvulsants
  • Topiramate
  • Fructose