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Original Investigation
August 5, 2019

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

Author Affiliations
  • 1Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark
  • 2Department of Dentistry and Oral Health, Aarhus University, Aarhus, Denmark
  • 3Department of Operative Dentistry and Periodontology, University Hospital, Ludwig-Maximilians-Universität München, München, Germany
  • 4Department of Pediatrics, Naestved Hospital, Naestved, Denmark
JAMA Pediatr. 2019;173(10):924-930. doi:10.1001/jamapediatrics.2019.2545
Key Points

Question  Is high-dose vitamin D supplementation during the third trimester of pregnancy associated with long-term dental health during childhood?

Findings  In a 6-year follow-up of a double-blind randomized clinical trial that included 623 pregnant women, high-dose vitamin D supplementation during third trimester was associated with reduced odds of enamel defects in the offspring by approximately 50%. No associations with caries were observed.

Meaning  Prenatal high-dose vitamin D supplementation may be a clinically relevant preventive intervention for enamel defects.


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 (COPSAC2010). 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 D3 (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 D3 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  ClinicalTrials.gov identifier: NCT00856947