TABLE 1.

Rates for Major Congenital Malformations across Recent Studies

Australian Registry (Monotherapy)

Valproate = 16.8%, Carbamazepine = 3.8%, Lamotrigine = 0%, Phenytoin = 5.9%

RR = 5.6 (2.42–12.92) for valproate vs other AEDs

Reference: Vajda et al. (11)

Finnish Birth Registry (Monotherapy)

Valproate = 10.7%; OR = 4.18 (2.31–7.57) vs controls

Carbamazepine = 3.5%

Reference: Artama et al. (12)

European Surveillance of Congenital Anomalies (EUROCAT) (Monotherapy)

No evidence of increased isolated orofacial clefts relative to other malformations for lamotrigine monotherapy.

Reference: Dolk et al. (22)

International Lamotrigine Registry (Polytherapy)

12.5% with valproate vs 2.7% no valproate

RR = 4.55 (1.63–12.69)

Reference: Cunnington et al. (13)

Neurodevelopmental Effects of Antiepileptic Drugs (NEAD Study) (Monotherapy: major malformations and fetal deaths)

Valproate = 20.3%, Carbamazepine = 8.2%, Lamotrigine = 1.0%, Phenytoin = 10.7%

RR = 4.59 (2.07–10.18) for valproate vs other AEDs

Reference: Meador et al. (14)

North America Registry (Monotherapy)

Phenobarbital = 6.5%; RR = 2 (0.9–4.5) vs other AEDs

Valproate = 10.7%, OR = 4.0 (2.1–7.4) vs other AEDs

Other AEDs = 2.9%

General population = 1.62%

Lamotrigine 2.7% (cleft lip/palate 0.73%)

Carbamazepine 2.6% (cleft lip/palate 0.023%; neural tube 0.014%)

Reference: Wyszynski et al., Holmes et al., Holmes et al., Hernandez-Diaz et al. (15,19,22,23)

Swedish Birth Registry (Monotherapy)

Valproate = 9.7%, Carbamazepine = 4.0%

OR = 2.51 (1.43–4.86) for valproate vs carbamazepine

Reference: Wide et al. (16)

UK Registry (Monotherapy)

Valproate = 6.2%, Carbamazepine = 2.2%, Lamotrigine = 3.2%

OR = 2.97 (1.65–5.35) for valproate vs carbamazepine

Reference: Morrow et al. (17)