Pregnancy-associated alterations in circulating vitamin D metabolites: higher total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D without increased free 25-hydroxyvitamin D
In brief
Pregnancy raises total vitamin D by 22 nmol/L, while free levels stay similar
In a laboratory study of more than 117,000 women, pregnancy was associated with higher total 25-hydroxyvitamin D and markedly higher total 1,25-dihydroxyvitamin D, especially later in gestation. Directly measured free 25-hydroxyvitamin D did not differ significantly, but it was available for far fewer women, so that finding needs confirmation before guiding interpretation in pregnancy.
- Journal
- Frontiers in endocrinology (Q1)
- Published
- 22 October 2026
- Study design
- Cross-sectional study
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Hui-Fang Zhang, Xin Chen, Jia-Yi Xiang, Ze-Yu Zhang, Yvonne Liu, Katrin Huesker, et al.
- PMID
- 42990895
- DOI
- 10.3389/fendo.2026.1957418
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 8 November 2026): Large laboratory study clarifies vitamin D metabolite interpretation in pregnancy
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)2D] 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)2D 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)2D 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)2D. 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.
Abstract as published, via PubMed.
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