Conflict of Interest: Mark W. Green, MD, is on the speakers' bureau for Zogenix; John D. Seeger, PharmD, DrPH, is a consultant for Optum Insight and WHISCON, LLC; Craig Peterson, MS, is employed by Vivus, Inc.; and Arun Bhattacharyya, PhD, is employed by Wolters Kluwer Pharma Solutions.
Utilization of Topiramate During Pregnancy and Risk of Birth Defects
Article first published online: 22 JUN 2012
© 2012 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 52, Issue 7, pages 1070–1084, July/August 2012
How to Cite
Green, M. W., Seeger, J. D., Peterson, C. and Bhattacharyya, A. (2012), Utilization of Topiramate During Pregnancy and Risk of Birth Defects. Headache: The Journal of Head and Face Pain, 52: 1070–1084. doi: 10.1111/j.1526-4610.2012.02190.x
Financial Support: This study was sponsored by Vivus, Inc.
- Issue published online: 3 JUL 2012
- Article first published online: 22 JUN 2012
- Accepted for publication May 2, 2012.
- major congenital malformations;
- oral cleft;
Objective.— To evaluate the risk of oral cleft and major congenital malformation occurrence in infants born to women exposed to topiramate in their first trimester of pregnancy compared with women who used other anti-epileptic drugs or those with disease states in which topiramate may have been used.
Methods.— Sourced from patients' pharmacy and medical claims from 2002 through 2010, this study identified infants born from mothers exposed to topiramate (n = 870) and other anti-epileptic drugs (n = 3615) in the first trimester of pregnancy. First trimester exposure was based on prescription dispensing dates and days supplied relative to infant birth date, accounting for premature delivery. Infants born to women with migraine without epilepsy (n = 26,865), women with epilepsy (n = 2607), and women with diabetes mellitus (n = 13,062), as well as randomly sampled women (n = 99,761), were used for comparison. Topiramate use was excluded from all groups with the exception of the topiramate and random sample cohorts. Non-anti-epileptic drug teratogens were excluded from each cohort (except random sample). Unadjusted relative risks and 95% confidence intervals for topiramate vs each comparator were calculated. Risks >1 indicate a higher risk with topiramate vs comparator, whereas risks <1 indicate a lower risk with topiramate vs comparator.
Results.— The frequency of oral clefts was 0.23% for topiramate use, 0.17% for other anti-epileptic drug use (topiramate vs comparator relative risk = 1.39 [95% confidence interval: 0.28-6.85]), 0.16% for migraineurs (1.47 [0.36-6.06]), 0.31% for epileptics (0.75 [0.16-3.52]), 0.26% for diabetics (0.88 [0.21-3.67]), and 0.16% for the random sample (1.44 [0.36-5.81]). The frequency of major congenital malformations was 4.33% for topiramate use, 3.21% for other anti-epileptic drugs (1.33 [0.92-1.90]), 3.79% for migraineurs (1.12 [0.81-1.55]), 4.33% for epileptics (0.98 [0.68-1.41]), 6.58% for diabetics (0.65 [0.47-0.89]), and 3.77% for the random sample (1.13 [0.82-1.55]).
Conclusions.— This retrospective study quantified the association between topiramate exposure during pregnancy and the risk of oral cleft or major congenital malformations, and suggested little or no increase in risk in comparison with exposure to other anti-epileptic drugs or to disease states, such as migraine, epilepsy, or diabetes. However, small numbers of events limit the strength of inferences.