Cardiac Malformations Are Increased in Infants of Mothers with Epilepsy

Abstract

We aimed to ascertain the prevalence of cardiac malformation (CM) and its association with antenatal exposure to an antiepileptic drug (AED) in infants of mothers with epilepsy (IMEs). Women with epilepsy (WWE) are enrolled in Kerala Registry of Epilepsy and Pregnancy (KREP) in the prepregnancy or early pregnancy period and are followed up with a standard protocol until the IMEs are 6 years old. At 3 months postpartum, a cardiologist, blinded to the AED exposure, carried out a clinical examination and echocardiography on all live-born babies. Patent foramen ovale (PFO) and interatrial septal defects of < 5 mm in size were excluded from CM. Details of maternal epilepsy, folate usage, AED exposure in the first trimester, and newborn characteristics were abstracted from the records of the KREP. We examined 462 babies. Maternal epilepsy was generalized in 201 (43.50%) or localization related in 241 (52.2%). The AED exposure was monotherapy in 262 (56.7%)--carbamazepine (112), valproate (71), phenobarbitone (43), phenytoin (31), and clonazepam (2)--and polytherapy in 126 (27.3%). Seventy-four infants (16.01%) had no AED exposure. There were 36 infants with CM (7.8%; 95% confidence interval: 5.5-10.6). CMs included atrial septal defect (26; 72.2%), tetrology of Fallot (3; 8.3%), patent ductus arteriosus and pulmonic stenosis (2 each; 5.6%), and ventricular septal defect, tricuspid regurgitation, transposition of great arteries (1 each; 2.8%). CMs were significantly more for IMEs with premature birth (p < .003). There was no association between CM and maternal age, epilepsy syndrome, seizure frequency during pregnancy, and folate use. CMs were more frequent with polytherapy (13; 10.3%) compared to monotherapy (17; 6.5%). Those with valproate exposure had a trend (not statistically significant) toward higher frequency of CM compared to IMEs on other AEDs as monotherapy.

Critical Evaluation of Antiepileptic Drugs in Epileptic Pregnant Women - Hungarian Experiences

“…Thus carbamazepine belongs to the group of AED with low teratogenic risk: 2.2 (1.1-4.6) [49] and 1.8 (0.8-3.7) [50]. Carbamazepine occurred twice as monotherapy and once as polytherapy (with valproate) in the origin of neural-tube defects in our material, however, 4 cases with cardiovascular CA after monotherapy of carbamazepine are worth noting, because similar finding was published in another study [51].…”

Association of certain chronic maternal diseases with the risk of specific congenital heart defects: a population-based study

“…Of 14 epileptic pregnant women, four were treated with carbamazepine alone, and two epileptic pregnant women received carbamazepine as part of polytherapy. These findings are in agreement with two previous reports which indicated the role of carbamazepine in the origin of CHDs [18,19].…”

Pregnancy outcome of 149 pregnancies in women with epilepsy: Experience from a tertiary care hospital

“…Recent evidence suggests that untreated epilepsy does not lead to increased malformations in the fetus [11]. However, the fetus of an epileptic mother taking anticonvulsant medication has an indisputably increased risk of congenital malformations.…”