Differential impact of antenatal exposure to antiseizure medications on motor and mental development in infants of women with epilepsy.

OBJECTIVE: We aimed to determine a possible association between motor and mental development in infants of women with epilepsy and antenatal exposure to antiseizure medication (ASM).

METHODS: Developmental paediatricians who were blinded to antenatal ASM exposure evaluated motor and mental development of infants (>12 months) using the Developmental Assessment Scale for Indian Infants (an Indian adaptation of the Bayley Scale of Infant Development). Motor (MODQ) and mental development quotients (MEDQ) were computed as ratios of respective developmental age to the chronological age of the child. We employed linear mixed models to study the relationship between antenatal exposure to ASM and the development quotients after adjustment for malformation status and age of the baby, maternal education and seizure type.

RESULTS: We studied 1,357 infants with mean age of 15.3±4.0 months (71.2% of all eligible infants). Infants were classified as having monotherapy or polytherapy, or unexposed in 840, 407 and 110 participants, respectively. The MEDQ of the polytherapy (92.9±14.9) and monotherapy (96.9±13.9) groups was lower than that of unexposed infants (99.8 12.5). Similarly, the MODQ of polytherapy (91.1±19.3) and monotherapy (96.6±17.5) groups was lower than that of unexposed infants (97.6 16.6). The differences in adjusted mean MEDQ were -7.4 (-11.4 to -4.3, p=0.001), -9.6 (-11.3 to -6.0, p=0.001) and -6.4 (-9.2 to -3.7, p=0.001) for valproate monotherapy, polytherapy with valproate and polytherapy without valproate, respectively. The adjusted mean MODQ also showed a similar trend. Those exposed to levetiracetam (n=62) had higher or similar adjusted MODQ (110.4±14.3; p=0.001) and MEDQ (104.3±9.1; p=0.09), compared to unexposed infants. A dose-dependent decrease in developmental indicators was observed for valproate and phenobarbitone.

SIGNIFICANCE: Antenatal exposure to ASM, especially valproate and phenobarbitone, adversely affects motor and mental development of exposed infants. Early developmental screening of high-risk infants is desirable.