What are the teratogenic risks of carbamazepine?

January 01, 0001

What are the teratogenic risks of carbamazepine?

Pregnancy and risk of birth defects can complicate treatment of many condition. Antiepileptic medications are known for their risk of teratogenicity. These Dutch, Danish, and UK researchers sought to characterize the risk of specific major congenital malformations with first trimester carbamazepine exposure. They performed a systematic review utilizing PubMed, Web of Science, and Embase for cohorts and case-control trials looking at this topic, along with EUROCAT Antiepileptic Study Database. This yielded eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98,075 registrations of malformations covering over 3.8 million births.

The researchers found: "The literature review yielded an overall prevalence for a major congenital malformation of 3.3% after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2), diaphragmatic hernia (0.9), or hypospadias (0.7) compared with no exposure to antiepileptic drugs. Further exploratory analysis suggested a higher risk of single ventricle and atrioventricular septal defect."

The researchers concluded: "Carbamazepine teratogenicity is relatively specific to spina bifida, though the risk is less than with valproic acid. Despite the large dataset, there was not enough power to detect moderate risks for some rare major congenital malformations."

This study characterizes the risk of specific congenital malformations with first trimester carbamazepine exposure, with the only statistically significant increased risk being for spina bifida.

For the full abstract, click here.

BMJ 341:c6581, 2 December 2010
© 2010 BMJ Publishing Group Ltd.
Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study. Janneke Jentink, Helen Dolk, Maria A Loane, et al. Correspondence to L de Jong-van den Berg: [email protected]

Category: N. Neurological, W. Pregnancy, Family Planning. Keywords: carbamazepine, first trimester, congenital malformations, spina bifida, anti-seizure medications, systematic review and case control study, journal watch.
Synopsis edited by Dr Paul Schaefer, Toledo, Ohio. Posted on Global Family Doctor 11 February 2011

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