{
  "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.\n\nMethods: 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.\n\nResults: 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.\n\nConclusions: 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.",
  "abstract_shown": true,
  "affiliations": [
    "Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology/Pneumology), University Medical Centre Mannheim, University of Heidelberg",
    "Institute for Clinical Research and Systems Medicine, Health and Medical University",
    "Department of Nephrology and Endocrinology, Klinikum Ernst von Bergmann",
    "Institute of Medical Diagnostics (IMD)",
    "Reproductive and Genetic Hospital of CITIC-Xiangya",
    "Institute 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"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hui-fang Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xin Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia-yi Xiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ze-yu Zhang"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yvonne Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Katrin Huesker"
    },
    {
      "affs": [
        3
      ],
      "name": "Volker von Baehr"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Saban Elitok"
    },
    {
      "affs": [
        0
      ],
      "name": "Bernhard Karl Krämer"
    },
    {
      "affs": [
        1
      ],
      "name": "Christoph Reichetzeder"
    },
    {
      "affs": [
        0,
        3,
        4,
        5
      ],
      "name": "Berthold Hocher"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ek9wvxzz8846b.bib",
  "cited_by": 0,
  "doi": "10.3389/fendo.2026.1957418",
  "fulltext_url": null,
  "id": "ek9wvxzz8846b",
  "issns": [
    "1664-2392"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1957418/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2734|Vitamin D Research Studies"
    ]
  ],
  "openalex": "W7223180943",
  "pdf_url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1957418/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ek9wvxzz8846b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:20Z",
      "native_id": "10.3389/fendo.2026.1957418",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1957418/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1664-2392",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "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",
  "title_text": "Pregnancy-associated alterations in circulating vitamin D metabolites: higher total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D without increased free 25-hydroxyvitamin D",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:20Z",
  "url": "https://research.draconitic.com/paper/ek9wvxzz8846b",
  "venue": "Frontiers in Endocrinology",
  "versions": []
}