Association between topiramate and zonisamide use during pregnancy and low birth weight.
OBJECTIVE
To assess the possible effects of topiramate and zonisamide use during pregnancy on fetal growth.


METHODS
The study population was the singleton liveborns born to women who enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2012. Data were collected through telephone interviews at enrollment, 7 months of gestation, and postpartum. The prevalence of small for gestational age at birth among neonates exposed to topiramate and to zonisamide when either was used as monotherapy during pregnancy was compared with that among neonates exposed to lamotrigine monotherapy, a weight-neutral therapy, and the most common antiepileptic drug in the Registry. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated with multivariable log-binomial regression to control for potential confounders.


RESULTS
Data were available for 347 topiramate, 98 zonisamide, and 1,581 lamotrigine-exposed neonates. The mean gestational length was 39 weeks for all comparison groups. Prenatal exposure to topiramate or zonisamide was associated with a mean lower birth weight of 221 and 202 g, respectively, and a mean lesser neonatal length of 1 cm as compared with lamotrigine exposure (p<.01). The prevalence of small for gestational age was 6.8% for lamotrigine, 17.9% for topiramate (RR 2.4, 95% CI 1.8-3.3) and 12.2% for zonisamide (RR 1.6, 0.9-2.8). Similar results were found when a group of 457 unexposed neonates was used as the reference.


CONCLUSIONS
Topiramate and zonisamide have been shown to reduce weight in adults. Our finding of a decrease in mean birth weight and length among neonates exposed in utero raises concern.


METHODS
II.
Department of Epidemiology, Harvard School of Public Health, and North American Antiepileptic Drug Pregnancy Registry, Massachusetts General Hospital for Children, Boston, Massachusetts; Loyola University Health System, Chicago, Illinois; the College of Physicians and Surgeons and Mailman School of Public Health, Columbia University, New York, New York; and Oregon Health and Science University, Portland, Oregon.
Sonia
S
Hernández-Díaz
Robert
R
Mittendorf
Caitlin R
CR
Smith
W Allen
WA
Hauser
Mark
M
Yerby
Lewis B
LB
Holmes
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D001724:Birth Weight / Q000187:drug effects*; D015331:Cohort Studies; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects*; D011247:Pregnancy; D012042:Registries; D000077236:Topiramate; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000077236:Topiramate; D005632:Fructose; D000078305:Zonisamide