{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:26:11Z","timestamp":1774452371995,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2017,1,28]],"date-time":"2017-01-28T00:00:00Z","timestamp":1485561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Observational studies suggest an adverse effect of maternal hypovitaminosis D during pregnancy. However, intervention studies failed to show convincing benefit from vitamin D supplementation during pregnancy. With analytical advances, vitamin D can now be measured in ten forms\u2014including as epimers\u2014which were thought to be biologically inactive, but can critically impair immunoassays. The aim of this commentary is to highlight the potential clinical and analytical significance of vitamin D epimers in the interpretation of vitamin D roles in pregnancy. Epimers may contribute a considerable proportion of total vitamin D\u2014especially in the neonate\u2014which renders the majority of common assays questionable. Furthermore, epimers have been suggested to have activity in laboratory studies, and evidence suggests that the fetus contributes significantly to epimer production. Maternal epimer levels contribute significantly to predict neonate circulating 25-hydroxyvitamin D concentrations. In conclusion, the existence of various vitamin D forms (such as epimers) has been established, and their clinical significance remains obscure. These results underscore the need for accurate measurements to appraise vitamin D status, in order to understand the current gap between observational and supplementation studies on the field.<\/jats:p>","DOI":"10.3390\/nu9020090","type":"journal-article","created":{"date-parts":[[2017,1,30]],"date-time":"2017-01-30T11:36:30Z","timestamp":1485776190000},"page":"90","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Road Not So Travelled: Should Measurement of Vitamin D Epimers during Pregnancy Affect Our Clinical Decisions?"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4225-2746","authenticated-orcid":false,"given":"Spyridon","family":"Karras","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 55535 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalliopi","family":"Kotsa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 55535 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Angeloudi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 55535 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pantelis","family":"Zebekakis","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 55535 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Declan","family":"Naughton","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00204-016-1804-x","article-title":"Vitamin D and chronic diseases: The current state of the art","volume":"91","author":"Muscogiuri","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1056\/NEJMp1608005","article-title":"Vitamin D Deficiency\u2014Is There Really a Pandemic?","volume":"375","author":"Manson","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.3945\/jn.116.231480","article-title":"Daily Cholecalciferol Supplementation during Pregnancy Alters Markers of Regulatory Immunity, Inflammation, and Clinical Outcomes in a Randomized Controlled Trial","volume":"146","author":"Zerofsky","year":"2016","journal-title":"J. Nutr."},{"key":"ref_4","first-page":"1","article-title":"Maternal vitamin D supplementation in pregnancy and offspring outcomes: A double-blind randomized placebo-controlled trial","volume":"14","author":"Sahoo","year":"2016","journal-title":"J. Bone Miner. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.earlhumdev.2016.07.011","article-title":"Vitamin D supplementation during pregnancy on infant anthropometric measurements and bone mass of mother-infant pairs: A randomized placebo clinical trial","volume":"103","author":"Vaziri","year":"2016","journal-title":"Early Hum. Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1177\/1759720X16656810","article-title":"Maternal vitamin D levels during pregnancy and neonatal health: Evidence to date and clinical implications","volume":"8","author":"Karras","year":"2016","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/all.12909","article-title":"Vitamin D supplementation during pregnancy and infancy reduces aeroallergen sensitization: A randomized controlled trial","volume":"71","author":"Grant","year":"2016","journal-title":"Allergy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1007\/s40618-015-0363-y","article-title":"Vitamin D during pregnancy: Why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review","volume":"38","author":"Karras","year":"2015","journal-title":"J. Endocrinol. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s00198-013-2468-5","article-title":"Maternal vitamin D status in pregnancy and offspring bone development: The unmet needs of vitamin D era","volume":"25","author":"Karras","year":"2004","journal-title":"Osteoporos. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"520S","DOI":"10.1093\/ajcn\/88.2.520S","article-title":"Vitamin D in pregnancy and lactation: Maternal, fetal, and neonatal outcomes from human and animal studies","volume":"88","author":"Kovacs","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1475-2891-12-77","article-title":"An observational study reveals that neonatal vitamin D is primarily determined by maternal contributions: Implications of a new assay on the roles of vitamin D forms","volume":"12","author":"Karras","year":"2013","journal-title":"Nutr. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.3945\/jn.116.229971","article-title":"Vitamin D Metabolism Varies among Women in Different Reproductive States Consuming the Same Intakes of Vitamin D and Related Nutrients","volume":"146","author":"Park","year":"2016","journal-title":"J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3945\/jn.115.220095","article-title":"APrON Study Team. Plasma 3-Epi-25-Hydroxycholecalciferol Can Alter the Assessment of Vitamin D Status Using the Current Reference Ranges for Pregnant Women and Their Newborns","volume":"146","author":"Aghajafari","year":"2016","journal-title":"J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Moln\u00e1r, F., Sig\u00fceiro, R., Sato, Y., Araujo, C., Schuster, I., Antony, P., Peluso, J., Muller, C., Mouri\u00f1o, A., and Moras, D. (2011). 1\u03b1,25(OH) 2\u20133-epi-vitamin D3, a natural physiological metabolite of vitamin D3: Its synthesis, biological activity and crystal structure with its receptor. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018124"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/1752-153X-6-112","article-title":"Method for simultaneous analysis of eight analogues of vitamin D using liquid chromatography tandem mass spectrometry","volume":"6","author":"Shah","year":"2012","journal-title":"Chem. Central. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1210\/jc.2013-2872","article-title":"Exploring the role of vitamin D in type 1 diabetes, rheumatoid arthritis, and Alzheimer disease: New insights from accurate analysis of 10 forms","volume":"99","author":"Shah","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1651-2227.1984.tb09933.x","article-title":"Plasma concentrations of vitamin D metabolites before and during treatment of vitamin D deficiency rickets in children","volume":"73","author":"Markestad","year":"1984","journal-title":"Acta Paediatr. Scand."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15897","DOI":"10.1074\/jbc.M311473200","article-title":"C-3 epimerization of vitamin D3 metabolites and further metabolism of C-3 epimers: 25-hydroxyvitamin D3 is metabolized to 3-epi-25-hydroxyvitamin D3 and subsequently metabolized through C-1alpha or C-24 hydroxylation","volume":"279","author":"Kamao","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1210\/jc.2006-0710","article-title":"C-3 epimers can account for a significant proportion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status","volume":"91","author":"Singh","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1475-2891-10-46","article-title":"Misleading measures in vitamin D analysis: A novel LC-MS\/MS assay to account for epimers and isobars","volume":"10","author":"Shah","year":"2011","journal-title":"Nutr. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cca.2014.12.036","article-title":"The 25-hydroxyvitamin D3 C-3 epimer: Distribution, correlates, and reclassification of 25-hydroxyvitamin D status in the population-based Atherosclerosis Risk in Communities Study (ARIC)","volume":"442","author":"Lutsey","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1210\/jc.2011-0584","article-title":"The C-3 epimer of 25-hydroxyvitamin D3 is present in adult serum","volume":"97","author":"Lensmeyer","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1007\/s00198-015-3125-y","article-title":"Serum C3 epimer of 25-hydroxyvitamin D and its determinants in adults: A national health examination survey in Thais","volume":"26","author":"Chailurkit","year":"2015","journal-title":"Osteoporos. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.3945\/jn.114.192419","article-title":"The 3 epimer of 25-hydroxycholecalciferol is present in the circulation of the majority of adults in a nationally representative sample and has endogenous origins","volume":"144","author":"Cashman","year":"2014","journal-title":"J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Djekic-Ivankovic, M., Lavery, P., Agellon, S., and Weiler, H.A. The C-3\u03b1 Epimer of 25-Hydroxycholecalciferol from Endogenous and Exogenous Sources Supports Normal Growth and Bone Mineral Density in Weanling Rats. Available online: http:\/\/jn.nutrition.org\/content\/early\/2016\/11\/23\/jn.116.231753.abstract.","DOI":"10.3945\/jn.116.231753"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R107","DOI":"10.1530\/JOE-14-0642","article-title":"Immunological role of vitamin D at the maternal-fetal interface","volume":"224","author":"Tamblyn","year":"2015","journal-title":"J. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.clinbiochem.2012.11.030","article-title":"Analytical measurement of serum 25-OH-vitamin D3, 25-OH-vitamin D2 and their C3-epimers by LC\u2013MS\/MS in infant and pediatric specimens","volume":"46","author":"Yazdanpanah","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/MPG.0000000000001001","article-title":"Dynamics of Vitamin D Metabolism in Maternal-Fetal Dyads","volume":"62","author":"Hanson","year":"2015","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1373\/clinchem.2011.180562","article-title":"25-hydroxyvitamin D: A difficult analyte","volume":"58","author":"Carter","year":"2012","journal-title":"Clin. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bone.2014.01.012","article-title":"Methodological issues in assessing plasma 25-hydroxyvitamin D concentration in newborn infants","volume":"61","author":"Gallo","year":"2014","journal-title":"Bone"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"136","DOI":"10.14310\/horm.2002.1263","article-title":"The interrelationship of serum 1, 25-dihydroxyvitamin, D.; 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in pregnancy at term: A meta-analysis","volume":"9","author":"Papapetrou","year":"2010","journal-title":"Hormones (Athens)"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.clinbiochem.2014.02.001","article-title":"Assessment of 3-epi-25-OH-D3 in preterm and full term infant samples and its relationship to demographic, anthropometric and biochemical determinants","volume":"47","year":"2014","journal-title":"Clin. Biochem."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/2\/90\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:27:10Z","timestamp":1760207230000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/2\/90"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,28]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,2]]}},"alternative-id":["nu9020090"],"URL":"https:\/\/doi.org\/10.3390\/nu9020090","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,28]]}}}