Neonatal vitamin D status and risk of childhood epilepsy

Epilepsy is a nervous system abnormality that may be caused by unknown exposures during fetal development. Studies have shown neuroprotective effects of early exposure to vitamin D in other neurological disorders, and seasonal variation in birth of children with epilepsy. We aimed to investigate if neonatal 25(OH)D₃ was associated with risk of childhood epilepsy.

This case-cohort study compared neonatal 25(OH)D₃ levels from children with epilepsy (n = 403) and a random selected cohort of controls (n = 1163), assessing the hazard of first epilepsy diagnosis between 1 and 4 years of age from a weighted Cox proportional hazard model. Analyses were adjusted for parental education, maternal age, maternal epilepsy, maternal ethnicity, and gestational age, and additionally for season of birth and smoking during pregnancy.

The mean (standard deviation [SD]) of neonatal 25(OH)D₃ levels were 30.8(19.6) nmol/L among cases and 28.5(19.4) nmol/L among the cohort. The hazard ratio (HR) of epilepsy was in a dose-response pattern higher among children from the highest neonatal 25(OH)D₃ quintiles (P-trend = .004). Results were unchanged after including season of birth in the analysis, where a significantly higher HR of epilepsy was observed among children in the two highest quintiles compared to children in the lowest quintile (Q4: HR_adj  1.62, 95% CI 1.07-2.47 and Q5: HR_adj  1.86, 95% CI 1.21-2.86).

In this study, the risk of childhood epilepsy increased with neonatal 25(OH)D₃ categories in a dose-response pattern, suggesting an association between a high neonatal 25(OH)D₃ and the risk of childhood epilepsy. Considering that adjusting for season of birth strengthened the results, we conclude that maternal intake of vitamin D, and not vitamin D from sun exposure, was the vitamin D source associated with epilepsy. Although we cannot, in the present study, control for compounds in the diet like pollutants or heavy metals, which may correlate with dietary vitamin D, future studies investigating fetal origin of epilepsy should focus on compounds correlating with vitamin D.