Maternal red blood cell folate and periconceptional folic acid supplementation are associated with neonatal brain maturation: a retrospective EEG-MRI study with term-equivalent imaging.

Maternal RBC folate sufficiency was associated with higher MRI myelination scores in neonates at term-equivalent age.

• Myelination score difference of Δ = 0.6 points (95% CI 0.3–0.9)
• Effect size η²p = 0.08, FDR-corrected q = 0.012
• MRI scored using a modified Kidokoro system at term-equivalent age (TEA) of 40 ± 1 weeks postmenstrual age (PMA)
• Inter-rater reliability for MRI scoring was ICC = 0.86
• RBC folate sufficiency defined as ≥ 906 nmol/L; deficiency as < 906 nmol/L

Maternal RBC folate sufficiency was associated with greater EEG maturation, including higher delta-brush frequency and greater aEEG continuity.

• Effect sizes η²p = 0.07–0.10 for EEG maturation measures
• FDR-corrected q ≤ 0.02 for both delta-brush frequency and aEEG continuity
• EEG metrics included Burdjalov aEEG background continuity and cycling, and conventional EEG delta-brush frequency
• Inter-rater reliability for EEG scoring was ICC = 0.83
• All EEG assessments were performed at TEA 40 ± 1 weeks PMA with readers blinded to group

Maternal RBC folate concentration was positively correlated with both MRI myelination scores and delta-brush frequency.

• Correlation with MRI myelination: r = 0.42 (95% CI 0.27–0.55), q < 0.01
• Correlation with delta-brush frequency: r = 0.37 (95% CI 0.21–0.51), q < 0.01
• Both correlations survived FDR correction using Benjamini-Hochberg procedure
• Study included 144 mother-infant pairs analyzed retrospectively from March 2022 to March 2024

Term infants demonstrated more advanced brain maturation than preterm infants on MRI and EEG measures at term-equivalent age.

• Main gestational age (GA) effect was statistically significant at q < 0.01
• Gestational age groups were defined as Preterm (< 37 weeks) and Term (≥ 37 weeks)
• Analyses used a two-factor design (GA × Folate) with two-way ANOVA and ANCOVA adjusting for sex and birthweight
• No GA × Folate interaction survived FDR correction

Documented periconceptional folic acid supplementation was more common among mothers with RBC folate sufficiency.

• Periconceptional folic acid supplementation (FAS) was a documented variable included in the two-factor study design
• The association suggests supplementation may contribute to achieving adequate folate status (RBC folate ≥ 906 nmol/L)
• The study was retrospective, analyzing 144 mother-infant pairs over a two-year period
• No GA × Folate interaction survived FDR correction, suggesting folate effects were present across both gestational age groups

The study used a retrospective two-factor design combining gestational age group and RBC folate status with standardized MRI and EEG scoring and multiple testing correction.

• 144 mother-infant pairs were analyzed retrospectively from March 2022 to March 2024
• Two-way ANOVA (GA × Folate) was used with Benjamini-Hochberg FDR control and effect sizes reported as η²p
• ANCOVA was additionally performed adjusting for sex and birthweight
• MRI readers and EEG scorers were blinded to group assignment
• MRI ICC = 0.86 and EEG ICC = 0.83 indicated good inter-rater reliability