The teratogenic risk after first trimester exposure to carbamazepine was determined from 210 pregnancies followed prospectively at the Israeli Teratogen Information Service, and Laboratory of Teratology, Hebrew University, Hadassah Medical School, and Ministry of Health, Jerusalem, Israel. Indications for treatment with carbamazepine included epilepsy (80%), trigeminal neuralgia or psychiatric disorder (13%), and were unspecified in 7% of women. Carbamazepine was the only AED in 68%, and the mean daily dose was 645 +/- 339 mg. Pregnancy outcome was compared with two controls, matched and general, unexposed to teratogenic agents. Mean maternal age was 29.6 years.

A twofold increase in the rate of major congenital anomalies occurred in the carbamazepine compared to the general control group (12/160 vs 18/560; relative risk 2.24). A similar trend occurred comparing the carbamazepine and matched control groups (12/160 vs 6/179; RR 2.37). Birth weight was reduced by approximately 250 g in carbamazepine-exposed compared to control infants. Elective terminations of pregnancy were more frequent in the carbamazepine group. The rate of major congenital anomalies was not significantly different in epileptic and nonepileptic or mono- and polytherapy groups. The congenital anomalies among carbamazepine-exposed infants showed no specific pattern. The rate of congenital heart defects in exposed infants was 2.9% compared to 1.6% in matched controls and 0.7% in the general control group. No cases of neural tube defect were recorded, an omission thought to reflect a sample size limitation. [1]

COMMENT. In this Israeli study, one of the largest series reported, first trimester carbamazepine (CBZ) exposure was associated with a twofold increase in the rate of major congenital anomalies and a reduced infant birth weight compared to controls. Neural tube defect, the most commonly reported teratogenic effect of CBZ, was surprisingly absent. (See Progress in Pediatric Neurology I and II, PNB Publishers, 1991(pp112-113) and 1994 (ppl09-112), for previous reports of AED teratogenicity, including spina bifida and CBZ). The 10,11-epoxide intermediate metabolite of CBZ has been implicated as the teratogenic agent. Oxcarbazepine (Trileptal®), the recently introduced congener of CBZ, has no epoxide metabolite, but undergoes reduction to form 10-monohydroxy derivative (MHD). Trileptal is reported to have no serious side effects and hopefully, this will include no teratogenicity.