A 2008 review concluded that CBZ monotherapy has one of the lowest risks of teratogenicity among antiepileptic treatments.2
The review summarized 9 studies that included women taking CBZ monotherapy as the exposed group. Six studies used epilepsy controls (n = 1613 for children born to epilepsy controls, n = 2533 for children exposed to CBZ monotherapy) and 3 used healthy controls (n = 2308 for children born to healthy controls, n = 542 for children exposed to CBZ monotherapy). Only 1 of the 9 studies had a relative risk ratio significantly greater than 1.0 for malformations when taking CBZ monotherapy compared with controls, and that was in one of the studies using healthy controls.5
Exposure to CBZ during pregnancy has been associated with an increased risk of neural tube defects (NTDs) (0.2% to 1% vs 0.1% in the general population),6–8
and its association with other major malformations has been clarified in a recent systematic review of 8 studies.9
The overall risk of all major congenital malformations was 3.3% with first-trimester CBZ monotherapy exposure (89 of 2680 exposed pregnancies, 95% CI 2.7% to 4.2%). The authors also conducted a case-controlled study using the EUROCAT database of 3 881 592 births and 98 075 major congenital malformations in Europe from 1995 to 2005. Within the database, spina bifida was significantly associated with exposure to CBZ monotherapy compared with no AED exposure (odds ratio [OR] 2.6, 95% CI 1.2 to 5.3), but the risk was significantly lower when CBZ was compared with valproic acid exposure (OR 0.2, 95% CI 0.1 to 0.6). Compared with no AED exposure, there was no significant association between exposure to CBZ monotherapy and total anomalous pulmonary venous return, cleft lip with or without cleft palate, diaphragmatic hernia, or hypospadias. Additionally, compared with other AED monotherapies (excluding valproic acid), there was no significant association between CBZ exposure and either spina bifida or hypospadias, and the risk was actually lower for cleft lip with or without cleft palate (OR 0.1, 95% CI 0.0 to 0.6).