{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T05:36:12Z","timestamp":1772516172171,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001825","name":"Danish Agency for Science and Higher Education","doi-asserted-by":"publisher","award":["0603-00453B"],"award-info":[{"award-number":["0603-00453B"]}],"id":[{"id":"10.13039\/501100001825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>This register-based national cohort study of 206,900 individuals investigated whether prenatal exposure to small extra doses of vitamin D from fortified margarine prevented inflammatory bowel disease (IBD) later in life; whether the risk of IBD varied according to month or season of birth; and finally, whether there was an interaction between exposure to extra D vitamin and month or season of birth. Fortification of margarine with vitamin D was mandatory in Denmark from the mid-1930s until 1st June 1985, when it was abolished. Two entire birth cohorts, each including two years, were defined: one exposed and one unexposed to the fortification policy for the entire gestation. All individuals were followed for 30 years from the day of birth for an IBD diagnosis in Danish hospital registers. Logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Odds for IBD was lower among those exposed to extra D vitamin compared to those unexposed, OR = 0.87 (95% CI: 0.79; 0.95). No association with month or season of birth was found. However, estimates suggested that particularly children born during autumn may have benefitted from the effect of small extra doses of vitamin D. This is, to our knowledge, the first study to explore if prenatal exposure to vitamin D from fortification influenced the risk of IBD. Our results suggest that prenatal exposure to small amounts of extra vitamin D from food fortification may protect against the development of IBD before 30 years of age.<\/jats:p>","DOI":"10.3390\/nu13041367","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:21:38Z","timestamp":1618831298000},"page":"1367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prenatal and Early Life Exposure to the Danish Mandatory Vitamin D Fortification Policy Might Prevent Inflammatory Bowel Disease Later in Life: A Societal Experiment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1630-3132","authenticated-orcid":false,"given":"Katrine S.","family":"Duus","sequence":"first","affiliation":[{"name":"Research Unit for Dietary Studies at The Parker Institute, Bispebjerg and Frederiksberg Hospital, Part of the Copenhagen University Hospital, 2000 Frederiksberg, Denmark"},{"name":"Focused Research Unit for Molecular Diagnostic and Clinical Research, Institute of Regional Health Research, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Moos","sequence":"additional","affiliation":[{"name":"Research Unit for Dietary Studies at The Parker Institute, Bispebjerg and Frederiksberg Hospital, Part of the Copenhagen University Hospital, 2000 Frederiksberg, Denmark"},{"name":"Focused Research Unit for Molecular Diagnostic and Clinical Research, Institute of Regional Health Research, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peder","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Research Unit for Dietary Studies at The Parker Institute, Bispebjerg and Frederiksberg Hospital, Part of the Copenhagen University Hospital, 2000 Frederiksberg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-2863","authenticated-orcid":false,"given":"Vibeke","family":"Andersen","sequence":"additional","affiliation":[{"name":"Focused Research Unit for Molecular Diagnostic and Clinical Research, Institute of Regional Health Research, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark"},{"name":"Institute of Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-4504","authenticated-orcid":false,"given":"Berit L.","family":"Heitmann","sequence":"additional","affiliation":[{"name":"Research Unit for Dietary Studies at The Parker Institute, Bispebjerg and Frederiksberg Hospital, Part of the Copenhagen University Hospital, 2000 Frederiksberg, Denmark"},{"name":"The Department of Public Health, Section for General Practice, University of Copenhagen, 1017 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kobayashi, T., Siegmund, B., Le Berre, C., Wei, S.C., Ferrante, M., Shen, B., Bernstein, C.N., Danese, S., Peyrin-Biroulet, L., and Hibi, T. (2020). Ulcerative colitis. Nat. Rev. Dis. Prim., 6.","DOI":"10.1038\/s41572-020-0205-x"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Roda, G., Chien Ng, S., Kotze, P.G., Argollo, M., Penaccione, R., Spinelli, A., Kaser, A., Peyrin-Biroulet, L., and Denese, S. (2020). Crohn\u2019s disease. Nat. Rev. Dis. Primers, 6.","DOI":"10.1038\/s41572-020-0156-2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrgastro.2015.150","article-title":"The global burden of IBD: From 2015 to 2025","volume":"12","author":"Kaplan","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/apt.13971","article-title":"The incidence of inflammatory bowel disease in Denmark 1980\u20132013: A nationwide cohort study","volume":"45","author":"Lophaven","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/nur.21813","article-title":"Symptom clusters in adults with inflammatory bowel disease","volume":"40","author":"Conley","year":"2017","journal-title":"Res. Nurs. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/php.13007","article-title":"Low Sun Exposure and Vitamin D Deficiency as Risk Factors for Inflammatory Bowel Disease, with a Focus on Childhood Onset","volume":"95","author":"Holmes","year":"2018","journal-title":"Photochem. Photobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1097\/MOG.0000000000000449","article-title":"Vitamin D in inflammatory bowel disease: More than just a supplement","volume":"34","author":"Gubatan","year":"2018","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3748\/wjg.v22.i3.933","article-title":"Protective links between vitamin D, inflammatory bowel disease and colon cancer","volume":"22","author":"Meeker","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1080\/10408398.2012.688897","article-title":"Vitamin D Bioavailability: State of the Art","volume":"55","author":"Borel","year":"2013","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.2147\/JIR.S63898","article-title":"Vitamin D and inflammatory diseases","volume":"7","author":"Agrawal","year":"2014","journal-title":"J. Inflamm. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6296","DOI":"10.3748\/wjg.v22.i27.6296","article-title":"Environmental risk factors for inflammatory bowel diseases: Evidence based literature review","volume":"22","author":"Abegunde","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4292\/wjgpt.v7.i1.112","article-title":"Influence of environmental factors in the development of inflammatory bowel diseases","volume":"7","author":"Legaki","year":"2016","journal-title":"World J. Gastrointest. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1053\/j.gastro.2019.04.016","article-title":"Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses","volume":"157","author":"Piovani","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1097\/MIB.0000000000000546","article-title":"Association Between Inflammatory Bowel Disease and Vitamin D Deficiency","volume":"21","author":"Pietropaoli","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/ibd\/izx050","article-title":"Prediagnostic Serum Vitamin D Levels and the Risk of Crohn\u2019s Disease and Ulcerative Colitis in European Populations: A Nested Case-Control Study","volume":"24","author":"Opstelten","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12020-015-0547-4","article-title":"Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease","volume":"50","author":"Skaaby","year":"2015","journal-title":"Endocrine"},{"key":"ref_17","unstructured":"Medical Research Council (Great Britain) and Environmental Epidemiology Unit (1993). Fetal and Infant Origins of Adult Disease: Papers written by the Medical Research Council Environmental Epidemiology Unit, University of Southampton, British Medical Journal."},{"key":"ref_18","unstructured":"Bhatia, A., and Bordoni, B. (2018). Embryology, Gastrointestinal. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_19","unstructured":"VanPutte, C., Regan, J., Russo, A., Tate, P., Stephens, T., and Seeley, R. (2013). Anatomy & Physiology, McGraw-Hill Science Engineering."},{"key":"ref_20","first-page":"774","article-title":"Early nutrition and immunity-progress and perspectives","volume":"96","author":"Calder","year":"2006","journal-title":"Br. J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3390\/nu4040259","article-title":"Sources and Determinants of Vitamin D Intake in Danish Pregnant Women","volume":"4","author":"Jensen","year":"2012","journal-title":"Nutrients"},{"key":"ref_22","unstructured":"Haraldsd\u00f3ttir, J., and Thaarup, S. (1989). Pohjoismaiden ministerineuvosto; Elintarvikevaliokunta. Tils\u00e6tning af Vitaminer og Mineraler til Levnedsmidler, Nordisk Ministerr\u00e5d."},{"key":"ref_23","unstructured":"Haraldsd\u00f3ttir, J., Holm, L., Jensen, J.H., and M\u00f8ller, A. (1986). Danskernes Kostvaner 1985, Ern\u00e6ringsenheden Levnedsmiddelstyrelsen."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1097\/MPG.0000000000002032","article-title":"Academic Stress May Contribute to the Onset of Pediatric Inflammatory Bowel Diseases","volume":"67","author":"Krishna","year":"2018","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1111\/j.1572-0241.2004.40058.x","article-title":"The Month of Birth is Linked to the Risk of Crohn\u2019s Disease in the Israeli Population","volume":"99","author":"Chowers","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1007\/s10620-008-0453-1","article-title":"Seasonality in Flares and Months of Births of Patients with Ulcerative Colitis in a Chinese Population","volume":"54","author":"Bai","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"661","DOI":"10.5009\/gnl.2013.7.6.661","article-title":"Seasonal Variation in Months of Birth and Symptom Flares in Korean Patients with Inflammatory Bowel Disease","volume":"7","author":"Jung","year":"2013","journal-title":"Gut Liver"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/1047-2797(93)90066-D","article-title":"Breast-feeding and maternal smoking in the etiology of Crohn\u2019s disease and ulcerative colitis in childhood","volume":"3","author":"Rigas","year":"1993","journal-title":"Ann. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1038\/ajg.2009.107","article-title":"Monthly and Seasonal Birth Patterns and the Occurrence of Crohn\u2019s Disease","volume":"104","author":"Angelucci","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/s00508-005-0391-2","article-title":"Seasonality of births and childhood inflammatory bowel disease","volume":"117","author":"Mikulecky","year":"2005","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1097\/01.MIB.0000163697.34592.d4","article-title":"Crohn\u2019s disease and month of birth","volume":"11","author":"Joossens","year":"2005","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/ibd.20730","article-title":"Date of birth in the occurrence of inflammatory bowel disease","volume":"15","author":"Sonnenberg","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1136\/gut.51.6.814","article-title":"No seasonality in month of birth of inflammatory bowel disease cases: A prospective population based study of British under 20 year olds","volume":"51","author":"Card","year":"2002","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1136\/gut.47.6.801","article-title":"Measles, month of birth, and Crohn\u2019s disease","volume":"47","author":"Haslam","year":"2000","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Disanto, G., Chaplin, G., Morahan, J.M., Giovannoni, G., Hypp\u00f6nen, E., Ebers, G.C., and Ramagopalan, S.V. (2012). Month of birth, vitamin D and risk of immune-mediated disease: A case control study. BMC Med., 10.","DOI":"10.1186\/1741-7015-10-69"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1136\/bmj.323.7318.907","article-title":"Does month of birth affect risk of Crohn\u2019s disease in childhood and adolescence?","volume":"323","author":"Pedersen","year":"2001","journal-title":"BMJ"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/0016-5085(91)90202-V","article-title":"The epidemiology of inflammatory bowel disease: A large, population-based study in Sweden","volume":"100","author":"Ekbom","year":"1991","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dharmaraj, R., Jaber, A., Arora, R., Hagglund, K., and Lyons, H. (2015). Seasonal variations in onset and exacerbation of inflammatory bowel diseases in children. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1702-y"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.cgh.2013.07.028","article-title":"Association Between Spring Season of Birth and Crohn\u2019s Disease","volume":"12","author":"Shaw","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1093\/oxfordjournals.aje.a116162","article-title":"Is There Clustering of Inflammatory Bowel Disease at Birth?","volume":"134","author":"Ekbom","year":"1991","journal-title":"Am. J. Epidemiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.mam.2008.08.005","article-title":"Geographic location and vitamin D synthesis","volume":"29","author":"Kimlin","year":"2008","journal-title":"Mol. Asp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"374","DOI":"10.3945\/ajcn.113.059469","article-title":"Randomized controlled trial of the effects of vitamin D\u2013fortified milk and bread on serum 25-hydroxyvitamin D concentrations in families in Denmark during winter: The VitmaD study","volume":"98","author":"Madsen","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jacobsen, R., Abrahamsen, B., Bauerek, M., Holst, C., Jensen, C.B., Knop, J., Raymond, K., Rasmussen, L.B., Stougaard, M., and I A S\u00f8rensen, T. (2013). The influence of early exposure to vitamin D for development of diseases later in life. BMC Public Health, 13.","DOI":"10.1186\/1471-2458-13-515"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1210\/en.2010-0089","article-title":"Vitamin D Deficiency in Mice Impairs Colonic Antibacterial Activity and Predisposes to Colitis","volume":"151","author":"Lagishetty","year":"2010","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s10620-015-3710-0","article-title":"Does Vitamin D Protect the Gut Mucosal Barrier? Mechanistic Insights from Experimental Colitis","volume":"60","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jsbmb.2010.03.050","article-title":"Developmental vitamin D3 deficiency induces alterations in immune organ morphology and function in adult offspring","volume":"121","author":"Harvey","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"927","DOI":"10.3109\/00365521.2016.1144218","article-title":"Perinatal vitamin D levels are not associated with later risk of developing pediatric-onset inflammatory bowel disease: A Danish case-cohort study","volume":"51","author":"Thorsen","year":"2016","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_48","unstructured":"Stougaard, M. (2017). Vitamin D from Food Fortification and Preeclampsia. [Ph.D. Thesis, Faculty of Health Sciences, University of Southern Denmark]."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3109\/00365529609031980","article-title":"Assessment of the diagnoses of Crohn\u2019s disease and ulcerative colitis in a Danish hospital information system","volume":"31","author":"Fonager","year":"1996","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_50","unstructured":"Nadelmann Pedersen, A. (2015). Danskernes Kostvaner 2011\u20132013: Hovedresultater, DTU F\u00f8devareinstituttet, Afdeling for Ern\u00e6ring. Available online: www.schultzboghandel.dk."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/4\/1367\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:53Z","timestamp":1760161793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/4\/1367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["nu13041367"],"URL":"https:\/\/doi.org\/10.3390\/nu13041367","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]}}}