Work

Pregnancy-associated alterations in circulating vitamin D metabolites: higher total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D without increased free 25-hydroxyvitamin D

Year: 2026

Type: article

Abstract: Background Interpretation of vitamin D biomarkers during pregnancy remains challenging because physiological adaptations alter total and free vitamin D metabolites differently, while evidence comparing multiple circulating vitamin D metabolites within the same clinical setting remains limited. Methods We conducted a large real-world laboratory-based cross-sectional study using routine clinical data from women aged 18–45 years tested at a German diagnostic center between 2014 and 2020. Total 25-hydroxyvitamin D [25(OH)D], free 25-hydroxyvitamin D, and total 1,25-dihydroxyvitamin D [1,25(OH) 2 D] concentrations were compared between pregnant and nonpregnant women and across gestation using age-adjusted regression models. Complementary random-effects meta-analyses were performed for free 25-hydroxyvitamin D and total 1,25-dihydroxyvitamin D. Results After exclusions, 101,454 nonpregnant and 16,017 pregnant women comprised the overall study population, with analyte-specific sample sizes reflecting availability in routine clinical practice. In age-adjusted analyses, pregnancy was associated with higher total 25(OH)D concentrations (adjusted difference 22.07 nmol/L; 95% CI, 21.50–22.63; P<0.001) and markedly higher total 1,25(OH) 2 D concentrations (adjusted difference 125.20 pmol/L; 95% CI, 115.39–135.02; P<0.001). Both metabolites were higher at later gestational stages in cross-sectional analyses. In contrast, directly measured free 25(OH)D did not differ significantly between pregnant and nonpregnant women (adjusted difference, -2.63 pmol/L; 95% CI, -8.99 to 3.74; P = 0.417). Complementary meta-analyses showed higher total 1,25(OH) 2 D and modestly lower free 25(OH)D concentrations during pregnancy; sensitivity analyses excluding the current cohort yielded similar overall patterns. Conclusions Pregnancy was associated with higher total 25(OH)D and markedly higher total 1,25(OH) 2 D. No statistically significant difference in free 25(OH)D was detected in the much smaller available subgroup; this finding should be considered exploratory and requires confirmation in larger studies. These results highlight the importance of analyte-specific interpretation of vitamin D biomarkers during pregnancy.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1957418