Maternal and neonatal vitamin D metabolite profiling and its long-term impact on childhood growth: findings from the KLOTHO birth cohort.

BACKGROUND

Vitamin D is increasingly recognized as a key modulator of growth, metabolism, and body composition in early life. However, the long-term impact of maternal vitamin D status and its multiple circulating forms on childhood anthropometry remains poorly understood. The KLOTHO cohort provides a unique opportunity to investigate these associations using detailed multi-form vitamin D profiles.

METHODS

Within the prospective KLOTHO cohort, serum concentrations of eight vitamin D metabolites [25(OH)D2, 25(OH)D3, 1α,25(OH)2D2, 1α,25(OH)2D3, 3-epi-25(OH)D2, 3-epi-25(OH)D3, D2, D3] were quantified at birth by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Anthropometric measurements were assessed at 10-11 years of age (height, weight, BMI, waist circumference, and skinfold thickness). Associations between log10-transformed metabolite levels and anthropometric outcomes were evaluated using Spearman's correlation and multivariable linear regression adjusted for available covariates (sex, birth weight, maternal BMI, and season). False discovery rate (FDR) correction was applied (q <0.10).

RESULTS

Among 98 children with available follow-up data, cord-blood vitamin D metabolite profiles showed several exploratory trends of association with anthropometric measures assessed at 10-11 years of age. Directionally consistent associations were observed primarily for D3-related metabolites and linear growth indices, as well as for selected adiposity-related measures. However, none of the observed associations demonstrated robust statistical significance after correction for multiple testing. All findings should therefore be interpreted as hypothesis-generating signals rather than confirmed long-term associations.

CONCLUSIONS

In this exploratory analysis, multidimensional profiling of vitamin D metabolites at birth identified preliminary trends linking D3-related metabolites with later childhood anthropometric measures. These findings are hypothesis-generating and underscore the need for larger, adequately powered longitudinal studies to clarify the role of early-life vitamin D metabolism in childhood growth.