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BMC Pediatrics
Published in: BMC Pediatrics 1/2017

Open Access 01-12-2017 | Study protocol

Towards evidence-based vitamin D supplementation in infants: vitamin D intervention in infants (VIDI) — study design and methods of a randomised controlled double-blinded intervention study

Authors: Otto Helve, Heli Viljakainen, Elisa Holmlund-Suila, Jenni Rosendahl, Helena Hauta-alus, Maria Enlund-Cerullo, Saara Valkama, Kati Heinonen, Katri Räikkönen, Timo Hytinantti, Outi Mäkitie, Sture Andersson

Published in: BMC Pediatrics | Issue 1/2017

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Abstract

Background

Vitamin D is important for bone mass accrual during growth. Additionally, it is considered a requirement for a multitude of processes associated with, for example, the development of immunity. Many countries apply vitamin D supplementation strategies in infants, but the guidelines are not based on scientific evidence and aim at prevention of rickets. It remains unclear whether the recommended doses are sufficient for the wide array of other effects of vitamin D. The VIDI trial performed in Finland is the first large randomised controlled study for evaluation of the effects of different vitamin D supplemental doses in infancy on:
1.
bone strength
 
2.
infections and immunity
 
3.
allergy, atopy and asthma
 
4.
cognitive development
 
5.
genetic regulation of mineral homeostasis
 

Methods/Design

VIDI, a randomised controlled double-blinded single-centre intervention study is conducted in infants from the age of 2 weeks to 24 months. Participants, recruited at Helsinki Maternity Hospital, are randomised to receive daily either 10 μg (400 IU) or 30 μg (1 200 IU) of vitamin D3 supplementation. Both groups are assessed at 6 months of age for calcium homeostasis, and at 12 and 24 months of age for parameters associated with bone strength, growth, developmental milestones, infections, immunity, atopy-related diseases, and genetic factors involved in these functions.

Discussion

The study enables evaluation of short and long term effects of supplemental vitamin D on growth, immune functions and skeletal and developmental parameters in infants, and the effects of genetic factors therein. The results enable institution of evidence-based guidelines for vitamin D supplementation in infancy.

Trial registration

ClinicalTrials.gov, NCT01723852, registration date 6.11.2012.
Appendix
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Literature
1.
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96(1):365–408.CrossRefPubMed
2.
3.
Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008;88(2):491S–9.PubMed
4.
Bouillon R, Bischoff-Ferrari H, Willett W. Vitamin D and health: perspectives from mice and man. J Bone Miner Res. 2008;23(7):974–9.CrossRefPubMed
5.
Hewison M. An update on vitamin D and human immunity. Clin Endocrinol. 2012;76(3):315–25.CrossRef
6.
Ross AC. The 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutr. 2011;14(5):938–9.CrossRefPubMed
7.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012;97(4):1153–8.CrossRefPubMed
8.
Viljakainen HT, Korhonen T, Hytinantti T, Laitinen EK, Andersson S, Makitie O, Lamberg-Allardt C. Maternal vitamin D status affects bone growth in early childhood--a prospective cohort study. Osteoporosis Int. 2011;22(3):883–91.CrossRef
9.
Pekkinen M, Viljakainen H, Saarnio E, Lamberg-Allardt C, Makitie O. Vitamin D is a major determinant of bone mineral density at school age. PloS one. 2012;7(7):e40090.CrossRefPubMedPubMedCentral
10.
Soininen S, Eloranta AM, Lindi V, Venalainen T, Zaproudina N, Mahonen A, Lakka TA: Determinants of serum 25-hydroxyvitamin D concentration in Finnish children: the Physical Activity and Nutrition in Children (PANIC) study. Br J Nutr. 2016;115(6):1080–91.
11.
12.
Viljakainen HT, Saarnio E, Hytinantti T, Miettinen M, Surcel H, Makitie O, Andersson S, Laitinen K, Lamberg-Allardt C. Maternal vitamin D status determines bone variables in the newborn. J Clin Endocrinol Metab. 2010;95(4):1749–57.CrossRefPubMed
13.
Mayranpaa MK, Tamminen IS, Kroger H, Makitie O. Bone biopsy findings and correlation with clinical, radiological, and biochemical parameters in children with fractures. J Bone Miner Res. 2011;26(8):1748–58.CrossRefPubMed
14.
Winzenberg T, Powell S, Shaw KA, Jones G. Effects of vitamin D supplementation on bone density in healthy children: systematic review and meta-analysis. BMJ. 2011;342:c7254.CrossRefPubMedPubMedCentral
15.
Cranney A, Weiler HA, O'Donnell S, Puil L. Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Am J Clin Nutr. 2008;88(2):513S–9.PubMed
16.
Pettifor JM, Prentice A. The role of vitamin D in paediatric bone health. Best Pract Res Clin Endocrinol Metab. 2011;25(4):573–84.CrossRefPubMed
17.
Soliman A, Salama H, Alomar S, Shatla E, Ellithy K, Bedair E. Clinical, biochemical, and radiological manifestations of vitamin D deficiency in newborns presented with hypocalcemia. Indian J Endocrinol Metab. 2013;17(4):697–703.CrossRefPubMedPubMedCentral
18.
Soliman AT, El-Dabbagh M, Adel A, Al Ali M, Aziz Bedair EM, Elalaily RK. Clinical responses to a mega-dose of vitamin D3 in infants and toddlers with vitamin D deficiency rickets. J Trop Pediatr. 2010;56(1):19–26.CrossRefPubMed
19.
Kumar GT, Sachdev HS, Chellani H, Rehman AM, Singh V, Arora H, Filteau S. Effect of weekly vitamin D supplements on mortality, morbidity, and growth of low birthweight term infants in India up to age 6 months: randomised controlled trial. BMJ. 2011;342:d2975.CrossRefPubMedPubMedCentral
20.
Wayse V, Yousafzai A, Mogale K, Filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr. 2004;58(4):563–7.CrossRefPubMed
21.
Karatekin G, Kaya A, Salihoglu O, Balci H, Nuhoglu A. Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers. Eur J Clin Nutr. 2009;63(4):473–7.CrossRefPubMed
22.
23.
24.
Khoo AL, Chai L, Koenen H, Joosten I, Netea M, van der Ven A. Translating the role of vitamin D(3) in infectious diseases. Crit Rev Microbiol. 2012;38(2):122–35.CrossRefPubMed
25.
Reinholz M, Ruzicka T, Schauber J. Vitamin D and its role in allergic disease. Clin Exp Allergy. 2012;42(6):817–26.PubMed
26.
Tiosano D, Wildbaum G, Gepstein V, Verbitsky O, Weisman Y, Karin N, Eztioni A. The role of vitamin D receptor in innate and adaptive immunity: a study in hereditary vitamin D-resistant rickets patients. J Clin Endocrinol Metab. 2013;98(4):1685–93.CrossRefPubMed
27.
28.
Ginde AA, Camargo Jr CA, Shapiro NI. Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection. Acad Emerg Med. 2011;18(5):551–4.CrossRefPubMed
29.
Gradel L, Merker M, Mueller B, Schuetz P. Screening and treatment of vitamin D deficiency in the emergency department - is there a benefit for medical inpatients? Am J Med. 2015;129(1):116e1–34.CrossRef
30.
McNally JD, Leis K, Matheson LA, Karuananyake C, Sankaran K, Rosenberg AM. Vitamin D deficiency in young children with severe acute lower respiratory infection. Ped Pulm. 2009;44(10):981–8.CrossRef
31.
Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010;91(5):1255–60.CrossRefPubMed
32.
Science M, Maguire JL, Russell ML, Smieja M, Walter SD, Loeb M. Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis. 2013;57(3):392–7.CrossRefPubMedPubMedCentral
33.
Thornton KA, Marin C, Mora-Plazas M, Villamor E. Vitamin D deficiency associated with increased incidence of gastrointestinal and ear infections in school-age children. Pediatr Infect Dis J. 2013;32(6):585–93.CrossRefPubMed
34.
Hugg T, Ruotsalainen R, Jaakkola MS, Pushkarev V, Jaakkola JJ. Comparison of allergic diseases, symptoms and respiratory infections between Finnish and Russian school children. Eur J Epidemiol. 2008;23(2):123–33.CrossRefPubMed
35.
Erkkola M, Kaila M, Nwaru BI, Kronberg-Kippila C, Ahonen S, Nevalainen J, Veijola R, Pekkanen J, Ilonen J, Simell O, et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp Allergy. 2009;39(6):875–82.CrossRefPubMed
36.
Liu X, Arguelles L, Zhou Y, Wang G, Chen Q, Tsai HJ, Hong X, Liu R, Price HE, Pearson C, et al. Longitudinal trajectory of vitamin D status from birth to early childhood in the development of food sensitization. Pediatr Res. 2013;74(3):321–6.CrossRefPubMedPubMedCentral
37.
Baiz N, Dargent-Molina P, Wark JD, Souberbielle JC, Annesi-Maesano I, EM-CCS Group. Cord serum 25-hydroxyvitamin D and risk of early childhood transient wheezing and atopic dermatitis. J Allergy Clin Immunol. 2014;133(1):147–53.CrossRefPubMed
38.
Chiu CY, Yao TC, Chen SH, Tsai MH, Tu YL, Hua MC, Yeh KW, Huang JL. Low cord blood vitamin D levels are associated with increased milk sensitization in early childhood. Pediatr Allergy Immunol. 2014;25(8):767–72.CrossRefPubMed
39.
Jones AP, Palmer D, Zhang G, Prescott SL. Cord blood 25-hydroxyvitamin D3 and allergic disease during infancy. Pediatrics. 2012;130(5):e1128–35.CrossRefPubMed
40.
Chawes BL, Bonnelykke K, Stokholm J, Vissing NH, Bjarnadottir E, Schoos AM, Wolsk HM, Pedersen TM, Vinding RK, Thorsteinsdottir S, 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):353–61.CrossRefPubMed
41.
Litonjua AA, Carey VJ, Laranjo N, Harshfield BJ, McElrath TF, O'Connor GT, Sandel M, Iverson Jr RE, Lee-Paritz A, Strunk RC, 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):362–70.CrossRefPubMed
42.
43.
Hypponen E, Berry DJ, Wjst M, Power C. Serum 25-hydroxyvitamin D and IgE - a significant but nonlinear relationship. Allergy. 2009;64(4):613–20.CrossRefPubMed
44.
Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology. 2012;79(13):1397–405.CrossRefPubMedPubMedCentral
45.
Etgen T, Sander D, Bickel H, Sander K, Forstl H. Vitamin D deficiency, cognitive impairment and dementia: a systematic review and meta-analysis. Dement Geriatr Cogn Disord. 2012;33(5):297–305.CrossRefPubMed
46.
Annweiler C, Montero-Odasso M, Llewellyn DJ, Richard-Devantoy S, Duque G, Beauchet O. Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis. 2013;37(1):147–71.PubMed
47.
Dean AJ, Bellgrove MA, Hall T, Phan WM, Eyles DW, Kvaskoff D, McGrath JJ. Effects of vitamin D supplementation on cognitive and emotional functioning in young adults--a randomised controlled trial. PloS one. 2011;6(11):e25966.CrossRefPubMedPubMedCentral
48.
Rossom RC, Espeland MA, Manson JE, Dysken MW, Johnson KC, Lane DS, LeBlanc ES, Lederle FA, Masaki KH, Margolis KL. Calcium and vitamin D supplementation and cognitive impairment in the women’s health initiative. J Am Geriatr Soc. 2012;60(12):2197–205.CrossRefPubMedPubMedCentral
49.
Zhu P, Tong SL, Hao JH, Tao RX, Huang K, Hu WB, Zhou QF, Jiang XM, Tao FB. Cord blood vitamin D and neurocognitive development are nonlinearly related in toddlers. J Nutr. 2015;145(6):1232–8.CrossRefPubMed
50.
McGrath J, Scragg R, Chant D, Eyles D, Burne T, Obradovic D. No association between serum 25-hydroxyvitamin D3 level and performance on psychometric tests in NHANES III. Neuroepidemiology. 2007;29(1–2):49–54.CrossRefPubMed
51.
Tolppanen AM, Williams D, Lawlor DA. The association of circulating 25-hydroxyvitamin D and calcium with cognitive performance in adolescents: cross-sectional study using data from the third National Health and Nutrition Examination Survey. Paediatr Perinat Epidemiol. 2011;25(1):67–74.CrossRefPubMed
52.
Tolppanen AM, Sayers A, Fraser WD, Lawlor DA. Association of serum 25-hydroxyvitamin D(3) and D(2) with academic performance in childhood: findings from a prospective birth cohort. J Epidemiol Community Health. 2012;66(12):1137–42.CrossRefPubMedPubMedCentral
53.
Nissen J, Rasmussen LB, Ravn-Haren G, Andersen EW, Hansen B, Andersen R, Mejborn H, Madsen KH, Vogel U. Common variants in CYP2R1 and GC genes predict vitamin D concentrations in healthy Danish children and adults. PloS one. 2014;9(2):e89907.CrossRefPubMedPubMedCentral
54.
Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, Kiel DP, Streeten EA, Ohlsson C, Koller DL, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376(9736):180–8.CrossRefPubMedPubMedCentral
55.
Pekkinen M, Saarnio E, Viljakainen HT, Kokkonen E, Jakobsen J, Cashman K, Makitie O, Lamberg-Allardt C. Vitamin D binding protein genotype is associated with serum 25-hydroxyvitamin D and PTH concentrations, as well as bone health in children and adolescents in Finland. PloS one. 2014;9(1):e87292.CrossRefPubMedPubMedCentral
56.
Morley R, Carlin JB, Pasco JA, Wark JD, Ponsonby AL. Maternal 25-hydroxyvitamin D concentration and offspring birth size: effect modification by infant VDR genotype. Eur J Clin Nutr. 2009;63(6):802–4.CrossRefPubMed
57.
Bodnar LM, Catov JM, Zmuda JM, Cooper ME, Parrott MS, Roberts JM, Marazita ML, Simhan HN. Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. J Nutr. 2010;140(5):999–1006.CrossRefPubMedPubMedCentral
58.
Fang Y, van Meurs JB, Rivadeneira F, van Schoor NM, van Leeuwen JP, Lips P, Pols HA, Uitterlinden AG. Vitamin D receptor gene haplotype is associated with body height and bone size. J Clin Endocrinol Metab. 2007;92(4):1491–501.CrossRefPubMed
59.
Arabi A, Zahed L, Mahfoud Z, El-Onsi L, Nabulsi M, Maalouf J, Fuleihan Gel H. Vitamin D receptor gene polymorphisms modulate the skeletal response to vitamin D supplementation in healthy girls. Bone. 2009;45(6):1091–7.CrossRefPubMed
60.
Molgaard C, Larnkjaer A, Cashman KD, Lamberg-Allardt C, Jakobsen J, Michaelsen KF. Does vitamin D supplementation of healthy Danish Caucasian girls affect bone turnover and bone mineralization? Bone. 2010;46(2):432–9.CrossRefPubMed
61.
Wicklow BA, Taback SP. Feasibility of a type 1 diabetes primary prevention trial using 2000 IU vitamin D3 in infants from the general population with increased HLA-associated risk. Ann N Y Acad Sci. 2000;2006(1079):310–2.
62.
Holmlund-Suila E, Viljakainen H, Hytinantti T, Lamberg-Allardt C, Andersson S, Makitie O. High-dose vitamin d intervention in infants--effects on vitamin d status, calcium homeostasis, and bone strength. J Clin Endocrinol Metab. 2012;97(11):4139–47.CrossRefPubMed
63.
Ireland A, Ferretti JL, Rittweger J. Imaging of the muscle-bone relationship. Curr Osteoporos Rep. 2014;12(4):486–95.CrossRefPubMed
64.
Denny FW, Collier AM, Henderson FW. Acute respiratory infections in day care. Rev Infect Dis. 1986;8(4):527–32.CrossRefPubMed
65.
Wald ER, Guerra N, Byers C. Frequency and severity of infections in day care: three-year follow-up. J Pediatr. 1991;118(4 Pt 1):509–14.CrossRefPubMed
Metadata
Title
Towards evidence-based vitamin D supplementation in infants: vitamin D intervention in infants (VIDI) — study design and methods of a randomised controlled double-blinded intervention study
Authors
Otto Helve
Heli Viljakainen
Elisa Holmlund-Suila
Jenni Rosendahl
Helena Hauta-alus
Maria Enlund-Cerullo
Saara Valkama
Kati Heinonen
Katri Räikkönen
Timo Hytinantti
Outi Mäkitie
Sture Andersson
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2017
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-017-0845-5

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