Pregnancy-associated alterations in circulating vitamin D metabolites: higher total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D without increased free 25-hydroxyvitamin D
6 affiliations
- 1Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology/Pneumology), University Medical Centre Mannheim, University of Heidelberg
- 2Institute for Clinical Research and Systems Medicine, Health and Medical University
- 3Department of Nephrology and Endocrinology, Klinikum Ernst von Bergmann
- 4Institute of Medical Diagnostics (IMD)
- 5Reproductive and Genetic Hospital of CITIC-Xiangya
- 6Institute of Reproductive and Stem Cell Engineering, National Health Commission (NHC) Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University
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.
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BibTeX
@article{zhang2026pregnancyassociated,
title = {{Pregnancy-associated alterations in circulating vitamin D metabolites: higher total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D without increased free 25-hydroxyvitamin D}},
author = {Hui-fang Zhang and Xin Chen and Jia-yi Xiang and Ze-yu Zhang and Yvonne Liu and Katrin Huesker and Volker von Baehr and Saban Elitok and Bernhard Karl Krämer and Christoph Reichetzeder and Berthold Hocher},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1957418},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1957418/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pregnancy-associated alterations in circulating vitamin D metabolites: higher total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D without increased free 25-hydroxyvitamin D
AU - Hui-fang Zhang
AU - Xin Chen
AU - Jia-yi Xiang
AU - Ze-yu Zhang
AU - Yvonne Liu
AU - Katrin Huesker
AU - Volker von Baehr
AU - Saban Elitok
AU - Bernhard Karl Krämer
AU - Christoph Reichetzeder
AU - Berthold Hocher
PY - 2026
DA - 2026/10/22
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1957418
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1957418/full
AB - 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.
SN - 1664-2392
ER -