Association of High-Dose Vitamin D Supplementation During Pregnancy With the Risk of Enamel Defects in Offspring: A 6-Year Follow-up of a Randomized Clinical Trial

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  • Pia Elisabeth Nørrisgaard, University of Copenhagen, Denmark
  • ,
  • Dorte Haubek
  • Jan Kuhnisch, Ludwig-Maximilians-Universität München, Tyskland
  • Bo L Chawes, University of Copenhagen, Denmark
  • ,
  • Jakob Stokholm, University of Copenhagen, Denmark
  • ,
  • Klaus Bønnelykke, University of Copenhagen, Denmark
  • ,
  • Hans Bisgaard, University of Copenhagen, Denmark, Danmark

Importance: Enamel defects of developmental origin affect up to 38% of schoolchildren and is recognized as a global public health challenge. The impaired enamel formation results in pain owing to hypersensitivity, posteruptive breakdowns, rapid caries progression, and extractions in some cases. The etiology is unknown; therefore, prevention is currently not possible. Objective: To assess the association of a high-dose vitamin D supplementation in pregnant women with enamel defects and caries in their offspring. Design, Setting, and Participants: Post hoc analysis of a double-blind, single-center, randomized clinical trial, the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort (COPSAC 2010). Enrollment began March 2009 and included 623 women recruited at 24 weeks of pregnancy and 588 of their children. A dental examination was completed at age 6 years in 496 of 588 children (84%). Data were analyzed in 2018. Intervention: High-dose vitamin D 3 (2400 IU/d; N = 315) or matching placebo tablets (N = 308) from pregnancy week 24 to 1 week post partum. In addition, all women received 400 IU/d of vitamin D 3 as part of standard care. Main Outcomes and Measures: Enamel defect was defined as having at least 1 molar affected by demarcated opacity, enamel breakdown, and/or atypical restoration. Caries was defined as decayed, missing, or filled surfaces in both the deciduous and permanent dentitions (World Health Organization standard). Results: The risk of enamel defects in the permanent dentition was lower in the offspring of mothers who received high-dose vitamin D supplementation during pregnancy compared with standard dose (15.1% [n = 26 of 172] vs 27.5% [n = 44 of 160]; odds ratio, 0.47; 95% CI, 0.27-0.81). A similar association was observed for the deciduous dentition (8.6% [n = 21 of 244] vs 15.9% [n = 40 of 252]; odds ratio, 0.50; 95% CI, 0.28-0.87). There was no association between supplementation and caries. Conclusions and Relevance: High-dose vitamin D supplementation during pregnancy was associated with approximately 50% reduced odds of enamel defects in the offspring. This suggests prenatal vitamin D supplementation as a preventive intervention for enamel defects, with a clinically important association with dental health. Trial Registration: identifier: NCT00856947.

TidsskriftJAMA Pediatrics
Sider (fra-til)924-930
Antal sider7
StatusUdgivet - okt. 2019


  • Enamel defects, molar-incisor-hypomineralization, demarcated 27 hypomineralized lesions, enamel hypomineralization, developmental defects, 28 vitamin D supplementation, randomized clinical trial, interventional study

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