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
8 affiliations
- 1Laboratory of Pharmacology, Medical School, Aristotle University, 54124 Thessaloniki, Greece
- 2Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Faculty of Health Sciences, Aristotle University, 54124 Thessaloniki, Greece
- 3Department of Biological Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece
- 4Assisting Nature Centre of Reproduction and Genetics, 57001 Thessaloniki, Greece
- 5Medical School, Aristotle University, 54124 Thessaloniki, Greece
- 6Department of Midwifery, Faculty of Health and Caring Sciences, University of West Attica, 12243 Athens, Greece
- 7Second Department of Surgery, Medical School, Aretaieio Athens Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
- 8Thermi Clinic, 57001 Thessaloniki, Greece
Abstract
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.
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BibTeX
@article{karras2026cord,
title = {{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}},
author = {Spyridon N. Karras and Dimitrios G. Goulis and Maria Dalamaga and Maria Kypraiou and Antonios Vlastos and Marios Anemoulis and Vikentia Harizopoulou and Georgios Mastorakos and Dimitrios Skoutas and Stergios A. Polyzos and Antonios Goulas},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18203361},
url = {https://www.mdpi.com/2072-6643/18/20/3361},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Spyridon N. Karras
AU - Dimitrios G. Goulis
AU - Maria Dalamaga
AU - Maria Kypraiou
AU - Antonios Vlastos
AU - Marios Anemoulis
AU - Vikentia Harizopoulou
AU - Georgios Mastorakos
AU - Dimitrios Skoutas
AU - Stergios A. Polyzos
AU - Antonios Goulas
PY - 2026
DA - 2026/10/01
JO - Nutrients
DO - 10.3390/nu18203361
UR - https://www.mdpi.com/2072-6643/18/20/3361
AB - 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.
SN - 2072-6643
ER -