Folate transfer across the placenta during late pregnancy in women with epilepsy: A cross-sectional, two-center study

In women with epilepsy who are treated with antiseizure medications (ASMs), folate concentrations in maternal serum may not be a good indicator of fetal folate supply, because ASMs can interfere with folate handling by the placenta. We aimed to assess the transplacental folate transfer at birth in persons with epilepsy in comparison to controls with no known epilepsy and identify factors affecting it.

This was a cross-sectional, two-center study, involving 22 pregnant women with epilepsy treated with ASMs, 10 nontreated pregnant women with epilepsy, and 19 control pregnant individuals with no known epilepsy. Maternal venous blood and umbilical cord blood samples were collected at delivery. Folate concentrations were measured using a validated chemiluminescence assay. ASM concentrations were analyzed in serum and umbilical cord blood.

Maternal and neonatal characteristics were generally comparable across the study groups, but cesarian sections were more frequent among controls (p < .001). Folate concentrations in maternal serum were lower than recommended levels in nine of 26 (35%) of women with epilepsy and eight of 19 (42%) controls. Median cord/maternal serum folate ratios were 1.51 (95% confidence interval [CI] = .92-6.35; n = 17) in women with epilepsy treated with ASMs and 2.02 (95% CI = 1.69-3.71; n = 19) in controls. In women with epilepsy, placental folate transfer was saturable (Cmax = 131.1 ng/mL, 95% CI = 96.4-190.5 ng/mL; Michaelis-Menten constant, Km = 32.6 ng/mL, 95% CI = 12.5-76.9 ng/mL; adjusted R² = .70). Predictability of cord values improved upon exclusion of preterm births (Cmax = 125.2 ng/mL, 95% CI = 97.4-164.7 ng/mL; Km =41.1 ng/mL, 95% CI = 22.4-71.1 ng/mL; adjusted R² = .78).

Folate delivery to the fetus during late pregnancy is primarily explained by its concentrations in maternal circulation. In persons with epilepsy, it may be saturable. The frequent apparent folate deficiency observed in our cohort highlights the importance of folate supplementation and monitoring of its levels in maternal circulation throughout pregnancy.