Use of topiramate in pregnancy and risk of oral clefts.
OBJECTIVE
The objective of this study was to evaluate the association between the use of monotherapy topiramate in pregnancy and cleft lip with or without cleft palate (CL/P) in the offspring.


METHODS
Data from the Slone Epidemiology Center Birth Defects Study (BDS) from 1997 to 2009 and the National Birth Defects Prevention Study (NBDPS) from 1997 to 2007 were analyzed. Conditional logistic regression was used to compare the first-trimester use of topiramate monotherapy to no antiepileptic drug use during the periconceptional period between the mothers of infants with CL/P and the mothers of controls for each study separately and in pooled data.


RESULTS
The BDS contained 785 CL/P cases and 6986 controls; the NBDPS contained 2283 CL/P cases and 8494 controls. The odds ratios (exact 95% confidence intervals) for the association between topiramate use and CL/P were 10.1 (1.1-129.2) in the BDS, 3.6 (0.7-20.0) in the NBDPS, and 5.4 (1.5-20.1) in the pooled data.


CONCLUSIONS
First-trimester use of topiramate may be associated with CL/P.
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. andreamargulis@post.harvard.edu
Andrea V
AV
Margulis
Allen A
AA
Mitchell
Suzanne M
SM
Gilboa
Martha M
MM
Werler
Murray A
MA
Mittleman
Robert J
RJ
Glynn
Sonia
S
Hernandez-Diaz
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D002971:Cleft Lip / Q000139:chemically induced* / Q000453:epidemiology; D002972:Cleft Palate / Q000139:chemically induced* / Q000453:epidemiology; D004827:Epilepsy / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D015994:Incidence; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000187:drug effects; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D015995:Prevalence; D012306:Risk; D000077236:Topiramate; D055815:Young Adult
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose