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

Educational Objective
To assess the association of a high-dose vitamin D supplementation in pregnant women with enamel defects and caries in their offspring.
1 Credit CME
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.

Abstract

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

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Article Information

Corresponding Author: Hans Bisgaard, MD, DMSc, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Alle 34, DK-2820 Gentofte, Denmark (bisgaard@copsac.com).

Accepted for Publication: April 24, 2019.

Published Online: August 5, 2019. doi:10.1001/jamapediatrics.2019.2545

Author Contributions: Dr Bisgaard had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Kühnisch scored the reliability of the dental registrations and the validation was performed at the Department of Conservative Dentistry and Periodontology, School of Dentistry, University of Munich. Drs Bisgaard and Bønnelykke contributed equally to the work.

Concept and design: Nørrisgaard, Kühnisch, Chawes, Stokholm, Bønnelykke, Bisgaard.

Acquisition, analysis, or interpretation of data: Nørrisgaard, Haubek, Chawes, Stokholm, Bønnelykke.

Drafting of the manuscript: Nørrisgaard, Kühnisch, Bønnelykke.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Nørrisgaard.

Obtained funding: Chawes, Bønnelykke.

Administrative, technical, or material support: Nørrisgaard, Haubek.

Supervision: Haubek, Kühnisch, Chawes, Stokholm, Bønnelykke, Bisgaard.

Conflict of Interest Disclosures: None reported.

Funding/Support: The Copenhagen Prospective Study on Asthma in Childhood (COPSAC) is funded by private and public research funds that are all listed on http://www.copsac.com. The Lundbeck Foundation, Danish State Budget, Danish Council for Strategic Research, Danish Council for Independent Research, and the Capital Region Research Foundation have provided core support for COPSAC.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: We are aware of and comply with recognized codes of good research practice, including the Danish Code of Conduct for Research Integrity. We comply with national and international rules on the safety and rights of patients and healthy individuals, including Good Clinical Practice as defined in the European Union's Directive on Good Clinical Practice, the International Conference on Harmonisation’s good clinical practice guidelines, and the Helsinki Declaration. We follow national and international rules on the processing of personal data, including the Danish Act on Processing of Personal Data and the practice of the Danish Data Inspectorate.

Additional Contributions: We thank the children and families of the Copenhagen Prospective Study on Asthma in Childhood 2010 cohort study for all their support and commitment. We acknowledge the unique efforts of the Copenhagen Prospective Study on Asthma in Childhood research team.

References
1.
Kassebaum  NJ, Bernabé  E, Dahiya  M, Bhandari  B, Murray  CJL, Marcenes  W.  Global burden of untreated caries: a systematic review and metaregression.  J Dent Res. 2015;94(5):650-658. doi:10.1177/0022034515573272PubMedGoogle ScholarCrossref
2.
Pitts  NB, Zero  DT, Marsh  PD,  et al.  Dental caries.  Nat Rev Dis Primers. 2017;3:17030. doi:10.1038/nrdp.2017.30PubMedGoogle ScholarCrossref
3.
Jälevik  B.  Prevalence and diagnosis of molar-incisor-hypomineralisation (MIH): a systematic review.  Eur Arch Paediatr Dent. 2010;11(2):59-64. doi:10.1007/BF03262714PubMedGoogle ScholarCrossref
4.
Kühnisch  J, Heitmüller  D, Thiering  E,  et al.  Proportion and extent of manifestation of molar-incisor-hypomineralizations according to different phenotypes.  J Public Health Dent. 2014;74(1):42-49. doi:10.1111/j.1752-7325.2012.00365.xPubMedGoogle ScholarCrossref
5.
Wogelius  P, Haubek  D, Poulsen  S.  Prevalence and distribution of demarcated opacities in permanent 1st molars and incisors in 6 to 8-year-old Danish children.  Acta Odontol Scand. 2008;66(1):58-64. doi:10.1080/00016350801926941PubMedGoogle ScholarCrossref
6.
Elfrink  MEC, Ghanim  A, Manton  DJ, Weerheijm  KL.  Standardised studies on molar incisor hypomineralisation (MIH) and hypomineralised second primary molars (HSPM): a need.  Eur Arch Paediatr Dent. 2015;16(3):247-255. doi:10.1007/s40368-015-0179-7PubMedGoogle ScholarCrossref
7.
Kühnisch  J, Kabary  L, Malyk  Y,  et al.  Relationship between caries experience and demarcated hypomineralised lesions (including MIH) in the permanent dentition of 15-year-olds.  Clin Oral Investig. 2018;22(5):2013-2019. doi:10.1007/s00784-017-2299-4PubMedGoogle ScholarCrossref
8.
Schwendicke  F, Elhennawy  K, Reda  S, Bekes  K, Manton  DJ, Krois  J.  Global burden of molar incisor hypomineralization.  J Dent. 2018;68:10-18. doi:10.1016/j.jdent.2017.12.002PubMedGoogle ScholarCrossref
9.
Elhennawy  K, Jost-Brinkmann  P-G, Manton  DJ, Paris  S, Schwendicke  F.  Managing molars with severe molar-incisor hypomineralization: a cost-effectiveness analysis within German healthcare.  J Dent. 2017;63:65-71. doi:10.1016/j.jdent.2017.05.020PubMedGoogle ScholarCrossref
10.
Alaluusua  S.  Aetiology of molar-incisor hypomineralisation: a systematic review.  Eur Arch Paediatr Dent. 2010;11(2):53-58. doi:10.1007/BF03262713PubMedGoogle ScholarCrossref
11.
Silva  MJ, Scurrah  KJ, Craig  JM, Manton  DJ, Kilpatrick  N.  Etiology of molar incisor hypomineralization: a systematic review.  Community Dent Oral Epidemiol. 2016;44(4):342-353. doi:10.1111/cdoe.12229PubMedGoogle ScholarCrossref
12.
Berdal  A, Papagerakis  P, Hotton  D, Bailleul-Forestier  I, Davideau  JL.  Ameloblasts and odontoblasts, target-cells for 1,25-dihydroxyvitamin D3: a review.  Int J Dev Biol. 1995;39(1):257-262.PubMedGoogle Scholar
13.
Mesbah  M, Nemere  I, Papagerakis  P,  et al.  Expression of a 1,25-dihydroxyvitamin D3 membrane-associated rapid-response steroid binding protein during human tooth and bone development and biomineralization.  J Bone Miner Res. 2002;17(9):1588-1596. doi:10.1359/jbmr.2002.17.9.1588PubMedGoogle ScholarCrossref
14.
Palacios  C, Gonzalez  L.  Is vitamin D deficiency a major global public health problem?  J Steroid Biochem Mol Biol. 2014;144(pt A):138-145. doi:10.1016/j.jsbmb.2013.11.003PubMedGoogle ScholarCrossref
15.
Hollis  BW, Wagner  CL.  Assessment of dietary vitamin D requirements during pregnancy and lactation.  Am J Clin Nutr. 2004;79(5):717-726. doi:10.1093/ajcn/79.5.717PubMedGoogle Scholar
16.
Kühnisch  J, Thiering  E, Kratzsch  J, Heinrich-Weltzien  R, Hickel  R, Heinrich  J; GINIplus study group; LISAplus study group.  Elevated serum 25(OH)-vitamin D levels are negatively correlated with molar-incisor hypomineralization.  J Dent Res. 2015;94(2):381-387. doi:10.1177/0022034514561657PubMedGoogle ScholarCrossref
17.
Schroth  RJ, Lavelle  C, Tate  R, Bruce  S, Billings  RJ, Moffatt  MEK.  Prenatal vitamin D and dental caries in infants.  Pediatrics. 2014;133(5):e1277-e1284. doi:10.1542/peds.2013-2215PubMedGoogle ScholarCrossref
18.
Kühnisch  J, Thiering  E, Heinrich-Weltzien  R, Hellwig  E, Hickel  R, Heinrich  J.  Fluoride/vitamin D tablet supplementation in infants-effects on dental health after 10 years.  Clin Oral Investig. 2017;21(7):2283-2290. doi:10.1007/s00784-016-2021-yPubMedGoogle ScholarCrossref
19.
Schroth  RJ, Rabbani  R, Loewen  G, Moffatt  ME.  Vitamin D and dental caries in children.  J Dent Res. 2016;95(2):173-179. doi:10.1177/0022034515616335PubMedGoogle ScholarCrossref
20.
Schroth  RJ, Levi  JA, Sellers  EA, Friel  J, Kliewer  E, Moffatt  MEK.  Vitamin D status of children with severe early childhood caries: a case-control study.  BMC Pediatr. 2013;13:174. doi:10.1186/1471-2431-13-174PubMedGoogle ScholarCrossref
21.
Bisgaard  H, Vissing  NH, Carson  CG,  et al.  Deep phenotyping of the unselected COPSAC2010 birth cohort study.  Clin Exp Allergy. 2013;43(12):1384-1394. doi:10.1111/cea.12213PubMedGoogle ScholarCrossref
22.
Bisgaard  H, Stokholm  J, Chawes  BL,  et al.  Fish oil-derived fatty acids in pregnancy and wheeze and asthma in offspring.  N Engl J Med. 2016;375(26):2530-2539. doi:10.1056/NEJMoa1503734PubMedGoogle ScholarCrossref
23.
Chawes  BL, Bønnelykke  K, Stokholm  J,  et al.  Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomized clinical trial.  JAMA. 2016;315(4):353-361. doi:10.1001/jama.2015.18318PubMedGoogle ScholarCrossref
24.
Wolsk  HM, Chawes  BL, Litonjua  AA,  et al.  Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: a combined analysis of two randomized controlled trials.  PLoS One. 2017;12(10):e0186657. doi:10.1371/journal.pone.0186657PubMedGoogle ScholarCrossref
25.
Lygidakis  NA, Wong  F, Jälevik  B, Vierrou  A-M, Alaluusua  S, Espelid  I.  Best clinical practice guidance for clinicians dealing with children presenting with molar-incisor-hypomineralisation (MIH): an EAPD policy document.  Eur Arch Paediatr Dent. 2010;11(2):75-81. doi:10.1007/BF03262716PubMedGoogle ScholarCrossref
26.
Sundhedsstyrelsen. Danish Health Authority; Central Odontologic Register (SCOR). https://www.sst.dk/da/Udgivelser/1999/Indberetning-paa-boerne--og-ungdomstandplejeomraadet---redegoerelse-vedroerende-revision-af-indberet. Accessed July 1, 2019.
27.
Litonjua  AA, Carey  VJ, Laranjo  N,  et al.  Effect of prenatal supplementation with vitamin d on asthma or recurrent wheezing in offspring by age 3 years: the VDAART randomized clinical trial.  JAMA. 2016;315(4):362-370. doi:10.1001/jama.2015.18589PubMedGoogle ScholarCrossref
28.
Bi  WG, Nuyt  AM, Weiler  H, Leduc  L, Santamaria  C, Wei  SQ.  Association between vitamin D supplementation during pregnancy and offspring growth, morbidity, and mortality: a systematic review and meta-analysis.  JAMA Pediatr. 2018;172(7):635-645. doi:10.1001/jamapediatrics.2018.0302PubMedGoogle ScholarCrossref
29.
Berdal  A, Hotton  D, Pike  JW, Mathieu  H, Dupret  JM.  Cell- and stage-specific expression of vitamin D receptor and calbindin genes in rat incisor: regulation by 1,25-dihydroxyvitamin D3.  Dev Biol. 1993;155(1):172-179. doi:10.1006/dbio.1993.1016PubMedGoogle ScholarCrossref
30.
Celio  MR, Norman  AW, Heizmann  CW.  Vitamin-D-dependent calcium-binding-protein and parvalbumin occur in bones and teeth.  Calcif Tissue Int. 1984;36(1):129-130. doi:10.1007/BF02405306PubMedGoogle ScholarCrossref
31.
Jones  KS, Assar  S, Harnpanich  D,  et al.  25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype.  J Clin Endocrinol Metab. 2014;99(9):3373-3381. doi:10.1210/jc.2014-1714PubMedGoogle ScholarCrossref
32.
van der Tas  JT, Elfrink  MEC, Heijboer  AC,  et al.  Foetal, neonatal and child vitamin D status and enamel hypomineralization.  Community Dent Oral Epidemiol. 2018;46(4):343-351. doi:10.1111/cdoe.12372PubMedGoogle ScholarCrossref
33.
Holick  MF.  Vitamin D deficiency.  N Engl J Med. 2007;357(3):266-281. doi:10.1056/NEJMra070553PubMedGoogle ScholarCrossref
34.
Jones  AP, Palmer  D, Zhang  G, Prescott  SL.  Cord blood 25-hydroxyvitamin D3 and allergic disease during infancy.  Pediatrics. 2012;130(5):e1128-e1135. doi:10.1542/peds.2012-1172PubMedGoogle ScholarCrossref
35.
Camargo  CA  Jr, Rifas-Shiman  SL, Litonjua  AA,  et al.  Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age.  Am J Clin Nutr. 2007;85(3):788-795. doi:10.1093/ajcn/85.3.788PubMedGoogle ScholarCrossref
36.
Devereux  G, Litonjua  AA, Turner  SW,  et al.  Maternal vitamin D intake during pregnancy and early childhood wheezing.  Am J Clin Nutr. 2007;85(3):853-859. doi:10.1093/ajcn/85.3.853PubMedGoogle ScholarCrossref
37.
Grossi  JA, Cabral  RN, Leal  SC.  Caries experience in children with and without molar-incisor hypomineralisation: a case-control study.  Caries Res. 2017;51(4):419-424. doi:10.1159/000477099PubMedGoogle ScholarCrossref
38.
Americano  GCA, Jacobsen  PE, Soviero  VM, Haubek  D.  A systematic review on the association between molar incisor hypomineralization and dental caries.  Int J Paediatr Dent. 2017;27(1):11-21. doi:10.1111/ipd.12233PubMedGoogle ScholarCrossref
39.
Crombie  FA, Manton  DJ, Weerheijm  KL, Kilpatrick  NM.  Molar incisor hypomineralization: a survey of members of the Australian and New Zealand Society of Paediatric Dentistry.  Aust Dent J. 2008;53(2):160-166. doi:10.1111/j.1834-7819.2008.00026.xPubMedGoogle ScholarCrossref
40.
Weerheijm  KL, Mejàre  I.  Molar incisor hypomineralization: a questionnaire inventory of its occurrence in member countries of the European Academy of Paediatric Dentistry (EAPD).  Int J Paediatr Dent. 2003;13(6):411-416. doi:10.1046/j.1365-263X.2003.00498.xPubMedGoogle ScholarCrossref
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