Serum NGF levels may be associated with intrauterine antiepileptic exposure-related developmental problems

It has been shown that maternal epilepsy and antiepileptic drug use during pregnancy have adverse developmental outcomes in children. The aim of this study was to investigate the developmental outcomes of maternal epilepsy and prenatal antiepileptic exposure. We also looked for the associations between serum levels of glial cell-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) and developmental outcomes.

This is a retrospective, nonrandomized, case-controlled study. Fifty-three children aged two to six years old with maternal epilepsy were included in the case group. Fifty-three age- and gender-matched children without maternal epilepsy were included in the control group. Developmental assessment was conducted using the Denver II Developmental Screening Test (DDST-II). Serum levels of NGF and GDNF were measured using an enzyme-linked immunosorbent assay (ELISA) kit.

Multiple regression analysis revealed that prenatal antiepileptic exposure was significantly associated with lower global developmental scores (B = -7.5, confidence interval (CI): -13.1; -1.9, p = 0.009) while periconceptional folate use was associated with a reduced risk for adverse developmental outcomes (B = 6.6, CI: 0.91; 12.3, p = 0.024). Children with prenatal antiepileptic exposure are at increased risk for global developmental delay (GDD) particularly for language domain (p = 0.018). We found a statistically significant positive correlation between NGF levels and global developmental scores (r = 0.302, p = 0.009). Serum levels of GDNF in children with maternal epilepsy were significantly lower than the children without maternal epilepsy (p = 0.025).

Prenatal antiepileptic exposure was related with the increased risk of GDD while periconceptional folate use was related with lower risk. Clinicians should inform all women in reproductive age with epilepsy about the possible benefits and risks of antiepileptic drug use during a possible pregnancy. Periconceptional folate use has protective effect on child development, and all women on antiepileptic drugs should be encouraged for periconceptional folate use. Serum NGF levels may be a promising biomarker for monitoring global development delay in at-risk population.