Cord Blood 3-Epi-25-Hydroxyvitamin D3 and Autism-Related Cognitive Traits at Age 10 Years: An Exploratory Secondary Analysis of the KLOTHO Birth Cohort

Background: The C3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] can be measured in maternal and umbilical cord circulation, but whether it is related to later neurodevelopment is unknown. Objective: To explore associations between cord 3-epi-25(OH)D3 and parent-reported autism-related trait domains at 10 years in the KLOTHO birth cohort. Methods: This secondary analysis used prospectively collected perinatal samples and 10-year questionnaire data. Vitamin D metabolites were quantified by liquid chromatography–tandem mass spectrometry with epimer separation. The Australian Scale for Asperger’s Syndrome was used dimensionally, not diagnostically. Spearman correlations, false-discovery-rate (FDR) correction across 13 unique bivariate comparisons, supportive linear regressions, sex-stratified analyses, and a stricter record-linkage sensitivity analysis were conducted. Results: Data were available for 87 offspring (41 boys and 46 girls). Cord 3-epi-25(OH)D3 was inversely associated with cognitive-domain score (Spearman ρ = −0.412; p < 0.001; Benjamini–Hochberg q = 0.001). The crude regression estimate was also inverse (B = −0.285; 95% CI, −0.458 to −0.112; p = 0.002), but the association attenuated after covariate adjustment and all adjusted confidence intervals included the null. A stricter linkage analysis remained significant (n = 84; ρ = −0.350; p = 0.001). The correlation was numerically stronger in boys than girls, but the between-sex comparison was not significant (p = 0.075). A positive correlation was also observed for social and emotional traits (ρ = 0.302; q = 0.023), indicating inconsistent directions across domains; the tertile analysis was non-significant. Conclusions: Cord 3-epi-25(OH)D3 was associated with lower cognitive-domain scores in unadjusted rank analyses, but the lack of stable adjusted linear evidence, inconsistent domain pattern, and small sample restrict interpretation. These findings are hypothesis-generating and do not imply causality, sex-specific effects, or clinical utility.