title: First trimester exposure to topiramate and the risk of oral clefts in the offspring: A systematic review and meta-analysis.
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.
authors: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, 555 University Ave, Toronto, ON M5G 1X8, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON M5S 3M2, Canada; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors: Abdulaziz M S
authors: AM
authors: Alsaad
authors: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, 555 University Ave, Toronto, ON M5G 1X8, Canada.
authors: Shahnaz Akthar
authors: SA
authors: Chaudhry
authors: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, 555 University Ave, Toronto, ON M5G 1X8, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON M5S 3M2, Canada. Electronic address: gkoren@sickkids.ca.
authors: Gideon
authors: G
authors: Koren
mesh_terms: D019440:Anti-Obesity Agents / Q000009:adverse effects*; D000927:Anticonvulsants / Q000009:adverse effects*; D002972:Cleft Palate / Q000139:chemically induced*; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects; D012306:Risk; D000077236:Topiramate
chemical_list: D019440:Anti-Obesity Agents; D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose
keywords: Epilepsy; Infants; Oral cleft; Pregnancy; Teratogenicity; Topamax; Topiramate