You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Different Vitamin D Supplementation Strategies: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Jason Zhu and Version 1 by Antonio Corsello.

Vitamin D (VD) is an essential micronutrient with multiple functions for human growth, and adequate intake should be guaranteed throughout life. However, VD insufficiency is observed in infants all over the world. Low VD concentration in the breast milk of non-supplemented mothers and low compliance to VD daily supplementation are the main causes of VD insufficiency, especially in the long term. Furthermore, VD supplementation dosages are still debated and differ by country. Different dosages and supplementation strategies result in similar VD sufficiency rates. Therefore, international guidelines may be revised in the future to offer multiple and different options of supplementation for specific settings and ages.

  • Vitamin D
  • Vitamin D supplementation
  • Vitamin D insufficiency

1. Introduction

Human breast milk, despite being the best choice for infant feeding, is generally lacking in proper amounts of Vitamin D (VD), with concentrations ranging from 10 to 80 IU/L in healthy lactating women [1]. Since the amount of breast milk VD is correlated with circulating levels of the vitamin, mothers with a poor VD status supply their infants with even less of these amounts. On the other hand, high serum levels of 25-hydroxyvitamin D (25(OH)D) in mothers correlate with higher breast milk amounts of VD [2,3,4][2][3][4]. The relevance of VD has changed in recent years, thanks to the knowledge of the many health outcomes VD has been associated with, especially regarding early development, bone health and immune system [5]. Therefore, by virtue of the VD functional role and the possible negative impact of its deficiency, it is important to ensure adequate levels in newborns, breastfed infants and toddlers, when a proper growth and nutrition is essential, and needs may change quickly [6]. For these reasons, the American Academy of Pediatrics and many European societies advocate VD supplementation to mothers, their children or both of them in order to prevent the risk of VD deficiency, which may be increased due to the limited sun exposure typical of the first months of life [7].
Furthermore, it is known that VD serum levels are maintained by cutaneous synthesis and oral intake, while VD metabolism is both renal and hepatic [8]. Nonetheless, multiple factors affect the overall VD status, with seasonality, clouds, altitude and latitude all having a direct impact on the sun angle and ultraviolet radiations [9]. Other factors that may significantly alter the VD status include genetic predispositions, skin type (skins with high concentrations of melanin need more time of sunlight exposure to achieve the same levels of VD sufficiency) and obesity [10]. In fact, both food absorption and cutaneous synthesis have been found to be linked to different quantities of adipose tissue [11]. This evidence could be related to the altered bioavailability of liposoluble vitamins in subjects with higher fat mass or high hepatic lipid content, which has been shown to be inversely correlated with VD serum concentrations [12].
A wide variety of methods and dosages of supplementation are described in the literature. Oral supplementation of 400 IU/day to all infants from few days after birth to at least 6 months of age is generally recommended [13]. However, a high prevalence of VD insufficiency is observed worldwide among infants, possibly due to caregivers’ poor compliance and acceptance of daily supplementation, with concurrent formulation heterogeneity [14,15,16][14][15][16]. Higher maternal postpartum supplementation or intermittent infant oral intake at higher doses could then represent a valid alternative [17,18][17][18]. However, the best supplementation strategy in the first period of life is still debated [19,20,21][19][20][21].

2. Current Work

The prevalence of VD deficiency observed among breastfed infants throughout the world is higher in those who lack an adequate sunlight exposure due to limited time spent outdoors or who do not follow regular VD supplementation regimens [48,49,50][22][23][24]. For all of these reasons, VD deficiency in infants and toddlers can be considered a frequent problem even in healthy subjects, with a prevalence ranging from 12% to 40% [51][25]. VD deficiency could represent a potential problem in infants exclusively breastfed by mothers having VD intakes of 400 IU/day, the amount normally assumed during pregnancy [40][26], and who do not receive direct and proper supplementation, as shown by a Norwegian study, which found a prevalence of 31% of VD deficiency in a population of 52 infants at 3 months of life, compared with a prevalence of 13% in their mothers at the same time [52][27]. VD deficiency can impact the quality of life of the child and particularly of the infant in the short and long term, and VD supplementation has been identified as a necessary and effective instrument for preventing VD deficiency. Possible consequences of VD deficiency include frequent infections, a higher risk of bone fractures and poor growth [53,54,55][28][29][30]. Indeed, the implementation of VD supplementation as a public health policy has been shown to reduce the prevalence of rickets in early childhood worldwide [56][31].
The choice of including subjects aging 12 to 36 months, rather than only infants, was made since they have different nutritional intakes, dietary habits and lifestyles. Indeed, just a few studies evaluated VD needs during the first years of life, and little is known on how the VD status changes after breastfeeding is discontinued. Additionally, the European Food Safety Authority set an adequate intake of 15 μg/d for children aged 1–17 years, not excluding the 12–24 months range of age and based on data mostly collected on adults [7,57][7][32]. Furthermore, because fortified milks are only recommended after the age of 12 months [58][33], and because a large number of factors affect the response to supplementation, such as baseline status at the end of breastfeeding, ethnicity compliance, latitude and diet, more studies on toddlers are needed to understand an eventually widespread VD deficiency at this age.
Several studies have been conducted on a possible association between the supplementation of VD and the reduced risk of developing autoimmune diseases, such as type 1 diabetes [59,60,61][34][35][36] and inflammatory bowel diseases [62[37][38][39][40],63,64,65], with conflicting results. Experimental data suggest that VD is able to modulate monocyte, macrophage and dendritic-cell response, and production of interleukins [66][41]. Recent studies suggest an involvement of VD in the suppression of T-lymphocyte proliferation and adaptive immune system, causing a shift from a Th1 to a Th2 phenotype and a subsequent alteration in T-cell differentiation and maturation, inducing T regulatory cells function and immune self-tolerance [67,68][42][43]. B lymphocytes also express VD receptors, which, when activated, can inhibit the differentiation into plasma cells and modulate immunoglobulin production [69][44]. All of these effects could explain the possible connection between variable VD serum levels and the probability of developing an autoimmune disease [70][45].
According to most of the international recommendations and global consensus about the prevention of rickets, all infants should be orally supplemented with 400 IU/day of VD from birth to 12 months of age, regardless of feeding and nutrition types [73][46]. The efficacy of trials conducted by daily administration may still suffer from the previously described bias of poor compliance in real-world experiences, resulting in lower effectiveness [74][47]. Considering that the compliance with daily VD supplementation in the first years of life is variable in different countries, and that rates of withdrawal and adherence change during the first months of life, an increased awareness about the correct posology and doses of VD administration is needed [22,23,24][48][49][50]. The main factors affecting VD levels in infants are related to the mother’s serum concentrations during pregnancy and lactation, the length of sun exposure of the child and the total intake assumed by diet or supplementation [75,76,77][51][52][53]. While fish, lipids and dairy products are the main sources of VD for humans, breast milk is a limited source of this micronutrient [1,78][1][54]. VD concentrations in breast milk are commonly expressed as antirachitic activity, which is calculated from the measurement of milk VD and 25(OH)D concentrations and then translated to biological activity using reference data [79][55]. Furthermore, the principal form of VD transferred from maternal circulation to breast milk is represented by cholecalciferol, with very few amounts of 25(OH)D passing directly via breast milk [80][56]. Another limiting step of VD passage in any form is the rapid conversion of cholecalciferol to 25(OH)D in mothers’ liver, which may be one of the main reasons for the low ratio between maternal serum 25(OH)D and breast milk VD concentration, which is approximately 0.2 [81][57]. Accordingly, mothers with low 25(OH)D serum concentrations supply even less VD to their infants, whereas higher VD levels in breast milk positively correlate with high serum levels of VD in mothers [2,3,4][2][3][4]. Therefore, if VD is not supplemented directly to the child, the mother’s VD intake during lactation should be higher than during pregnancy, when the ratio between serum and cord blood levels is in the range 0.5–0.8 [82,83][58][59]. According to the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines, all infants during the first year of life should receive 400 IU/day oral supplementation of VD, resulting in a minimal serum concentration of 20 ng/mL [84][60]. Beyond this age, seasonal variations in sunlight should be considered within a national policy for supplementation or fortification. Nevertheless, there is evidence that infants who receive a mixture of human milk and formula should also receive a VD supplement of 400 IU/day to ensure adequate intakes and support circulating VD [85][61]. As infants and toddlers are weaned from breastfeeding and/or formula, fortified milk and formulae or continuous VD supplementation should be encouraged to provide at least 400 IU/day of VD [58][33]. As an example, it has been shown that formula-fed infants receiving more than 1 L of VD-enriched formula do not need a higher VD intake through supplements [85,86][61][62]. To promote compliance to VD supplements, the fortification of commonly used food products has also been suggested [36,37,87][63][64][65]. Indeed, VD fortified products may be more efficient than intermittent supplements in maintaining adequate stores [37][64]. Enriched milk could represent an effective method of delivering VD because of its wide availability and acceptance. Accordingly, a prospective, randomized, double-blind study conducted in Germany on 92 children between 2 and 6 years of age has shown that consumption of milk fortified with VD can be a simple and safe nutritional measure to prevent decreasing serum 25(OH)D concentrations in periods or places with poor sunlight [88][66].

References

  1. Dawodu, A.; Tsang, R.C. Maternal Vitamin D Status: Effect on Milk Vitamin D Content and Vitamin D Status of Breastfeeding Infants. Adv. Nutr. 2012, 3, 353–361.
  2. Tsugawa, N.; Nishino, M.; Kuwabara, A.; Ogasawara, H.; Kamao, M.; Kobayashi, S.; Yamamura, J.; Higurashi, S. Comparison of Vitamin D and 25-Hydroxyvitamin D Concentrations in Human Breast Milk between 1989 and 2016–2017. Nutrients 2021, 13, 573.
  3. Anusha, K.; Hettiaratchi, U.; Gunasekera, D.; Prathapan, S.; Liyanage, G. Maternal Vitamin D Status and Its Effect on Vitamin D Levels in Early Infancy in a Tertiary Care Centre in Sri Lanka. Int. J. Endocrinol. 2019, 2019, 9017951.
  4. Jan Mohamed, H.J.; Rowan, A.; Fong, B.; Loy, S.-L. Maternal Serum and Breast Milk Vitamin D Levels: Findings from the Universiti Sains Malaysia Pregnancy Cohort Study. PLoS ONE 2014, 9, e100705.
  5. Zmijewski, M.A. Vitamin D and Human Health. Int. J. Mol. Sci. 2019, 20, 145.
  6. Savarino, G.; Corsello, A.; Corsello, G. Macronutrient Balance and Micronutrient Amounts through Growth and Development. Ital. J. Pediatr. 2021, 47, 109.
  7. Lee, J.Y.; So, T.-Y.; Thackray, J. A Review on Vitamin D Deficiency Treatment in Pediatric Patients. J. Pediatr. Pharmacol. Ther. 2013, 18, 277–291.
  8. Bikle, D.D. Vitamin D Metabolism, Mechanism of Action, and Clinical Applications. Chem. Biol. 2014, 21, 319–329.
  9. Engelsen, O. The Relationship between Ultraviolet Radiation Exposure and Vitamin D Status. Nutrients 2010, 2, 482–495.
  10. Tsiaras, W.G.; Weinstock, M.A. Factors Influencing Vitamin D Status. Acta Derm. Venereol. 2011, 91, 115–124.
  11. Migliaccio, S.; Di Nisio, A.; Mele, C.; Scappaticcio, L.; Savastano, S.; Colao, A. Obesity and Hypovitaminosis D: Causality or Casualty? Int. J. Obes. Suppl. 2019, 9, 20–31.
  12. Sun, X.; Cao, Z.-B.; Tanisawa, K.; Oshima, S.; Higuchi, M. Serum 25-Hydroxyvitamin D Concentrations Are Inversely Correlated with Hepatic Lipid Content in Male Collegiate Football Athletes. Nutrients 2018, 10, 942.
  13. Onal, H.; Adal, E.; Alpaslan, S.; Ersen, A.; Aydin, A. Is Daily 400 IU of Vitamin D Supplementation Appropriate for Every Country: A Cross-Sectional Study. Eur. J. Nutr. 2010, 49, 395–400.
  14. Almeida, A.C.F.; de Paula, F.J.A.; Monteiro, J.P.; Nogueira-de-Almeida, C.A.; Del Ciampo, L.A.; Aragon, D.C.; Ferraz, I.S. Do All Infants Need Vitamin D Supplementation? PLoS ONE 2018, 13, e0195368.
  15. Haimi, M.; Kremer, R. Vitamin D Deficiency/Insufficiency from Childhood to Adulthood: Insights from a Sunny Country. World J. Clin. Pediatr. 2017, 6, 1–9.
  16. Lava, S.A.G.; Caccia, G.; Osmetti-Gianini, S.; Simonetti, G.D.; Milani, G.P.; Falesi, M.; Bianchetti, M.G. Acceptance of Two Liquid Vitamin D₃ Formulations among Mothers with Newborn Infants: A Randomized, Single-Blind Trial. Eur. J. Pediatr. 2011, 170, 1559–1562.
  17. Tan, M.L.; Abrams, S.A.; Osborn, D.A. Vitamin D Supplementation for Term Breastfed Infants to Prevent Vitamin D Deficiency and Improve Bone Health. Cochrane Database Syst. Rev. 2020, 2020, CD013046.
  18. O’Callaghan, K.M.; Taghivand, M.; Zuchniak, A.; Onoyovwi, A.; Korsiak, J.; Leung, M.; Roth, D.E. Vitamin D in Breastfed Infants: Systematic Review of Alternatives to Daily Supplementation. Adv. Nutr. 2020, 11, 144–159.
  19. Fiscaletti, M.; Stewart, P.; Munns, C. The Importance of Vitamin D in Maternal and Child Health: A Global Perspective. Public Health Rev. 2017, 38, 19.
  20. Dalle Carbonare, L.; Valenti, M.T.; Del Forno, F.; Caneva, E.; Pietrobelli, A. Vitamin D: Daily vs. Monthly Use in Children and Elderly-What Is Going On? Nutrients 2017, 9, 652.
  21. Dalle Carbonare, L.; Valenti, M.T.; Del Forno, F.; Piacentini, G.; Pietrobelli, A. Vitamin D Daily versus Monthly Administration: Bone Turnover and Adipose Tissue Influences. Nutrients 2018, 10, 1934.
  22. Ahrens, K.A.; Rossen, L.M.; Simon, A.E. Adherence to Vitamin D Recommendations Among US Infants Aged 0 to 11 Months, NHANES, 2009 to 2012. Clin. Pediatr. 2016, 55, 555–556.
  23. Balasubramanian, S. Vitamin D Deficiency in Breastfed Infants & the Need for Routine Vitamin D Supplementation. Indian J. Med. Res. 2011, 133, 250–252.
  24. Dawodu, A.; Davidson, B.; Woo, J.G.; Peng, Y.-M.; Ruiz-Palacios, G.M.; de Guerrero, M.L.; Morrow, A.L. Sun Exposure and Vitamin D Supplementation in Relation to Vitamin D Status of Breastfeeding Mothers and Infants in the Global Exploration of Human Milk Study. Nutrients 2015, 7, 1081–1093.
  25. Gordon, C.M.; Feldman, H.A.; Sinclair, L.; Williams, A.L.; Kleinman, P.K.; Perez-Rossello, J.; Cox, J.E. Prevalence of Vitamin D Deficiency Among Healthy Infants and Toddlers. Arch. Pediatr. Adolesc. Med. 2008, 162, 505–512.
  26. Hollis, B.W.; Wagner, C.L.; Howard, C.R.; Ebeling, M.; Shary, J.R.; Smith, P.G.; Taylor, S.N.; Morella, K.; Lawrence, R.A.; Hulsey, T.C. Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial. Pediatrics 2015, 136, 625–634.
  27. Gjerde, J.; Kjellevold, M.; Dahl, L.; Berg, T.; Bøkevoll, A.; Markhus, M.W. Validation and Determination of 25(OH) Vitamin D and 3-Epi25(OH)D3 in Breastmilk and Maternal- and Infant Plasma during Breastfeeding. Nutrients 2020, 12, 2271.
  28. Anderson, L.N.; Heong, S.W.; Chen, Y.; Thorpe, K.E.; Adeli, K.; Howard, A.; Sochett, E.; Birken, C.S.; Parkin, P.C.; Maguire, J.L.; et al. Vitamin D and Fracture Risk in Early Childhood: A Case-Control Study. Am. J. Epidemiol. 2017, 185, 1255–1262.
  29. Aranow, C. Vitamin D and the Immune System. J. Investig. Med. 2011, 59, 881–886.
  30. Effects of Vitamin D on Linear Growth and Other Health Outcomes among Children under 5 Years of Age. Available online: https://www.cochrane.org/CD012875/BEHAV_effects-vitamin-d-linear-growth-and-other-health-outcomes-among-children-under-5-years-age (accessed on 14 January 2022).
  31. Saggese, G.; Vierucci, F.; Prodam, F.; Cardinale, F.; Cetin, I.; Chiappini, E.; De Angelis, G.L.; Massari, M.; Miraglia Del Giudice, E.; Miraglia Del Giudice, M.; et al. Vitamin D in Pediatric Age: Consensus of the Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics, Jointly with the Italian Federation of Pediatricians. Ital. J. Pediatr. 2018, 44, 1–40.
  32. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Dietary Reference Values for Vitamin D. EFSA J. 2016, 14, e04547.
  33. Verduci, E.; Di Profio, E.; Corsello, A.; Scatigno, L.; Fiore, G.; Bosetti, A.; Zuccotti, G.V. Which Milk during the Second Year of Life: A Personalized Choice for a Healthy Future? Nutrients 2021, 13, 3412.
  34. Stene, L.C.; Joner, G. Use of Cod Liver Oil during the First Year of Life Is Associated with Lower Risk of Childhood-Onset Type 1 Diabetes: A Large, Population-Based, Case-Control Study. Am. J. Clin. Nutr. 2003, 78, 1128–1134.
  35. Marjamäki, L.; Niinistö, S.; Kenward, M.G.; Uusitalo, L.; Uusitalo, U.; Ovaskainen, M.-L.; Kronberg-Kippilä, C.; Simell, O.; Veijola, R.; Ilonen, J.; et al. Maternal Intake of Vitamin D during Pregnancy and Risk of Advanced Beta Cell Autoimmunity and Type 1 Diabetes in Offspring. Diabetologia 2010, 53, 1599–1607.
  36. Zipitis, C.S.; Akobeng, A.K. Vitamin D Supplementation in Early Childhood and Risk of Type 1 Diabetes: A Systematic Review and Meta-Analysis. Arch. Dis. Child. 2008, 93, 512–517.
  37. Lim, W.-C.; Hanauer, S.B.; Li, Y.C. Mechanisms of Disease: Vitamin D and Inflammatory Bowel Disease. Nat. Clin. Pract. Gastroenterol. Hepatol. 2005, 2, 308–315.
  38. Limketkai, B.N.; Mullin, G.E.; Limsui, D.; Parian, A.M. Role of Vitamin D in Inflammatory Bowel Disease. Nutr. Clin. Pract. Off. Publ. Am. Soc. Parenter. Enter. Nutr. 2017, 32, 337–345.
  39. Del Pinto, R.; Pietropaoli, D.; Chandar, A.K.; Ferri, C.; Cominelli, F. Association Between Inflammatory Bowel Disease and Vitamin D Deficiency: A Systematic Review and Meta-Analysis. Inflamm. Bowel Dis. 2015, 21, 2708–2717.
  40. Zhao, J.; Wang, Y.; Gu, Q.; Du, Z.; Chen, W. The Association between Serum Vitamin D and Inflammatory Bowel Disease. Medicine 2019, 98, e15233.
  41. Dankers, W.; Colin, E.M.; van Hamburg, J.P.; Lubberts, E. Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. Front. Immunol. 2016, 7, 697.
  42. Bizzaro, G.; Shoenfeld, Y. Vitamin D and Autoimmune Thyroid Diseases: Facts and Unresolved Questions. Immunol. Res. 2015, 61, 46–52.
  43. Dimeloe, S.; Nanzer, A.; Ryanna, K.; Hawrylowicz, C. Regulatory T Cells, Inflammation and the Allergic Response—The Role of Glucocorticoids and Vitamin D. J. Steroid Biochem. Mol. Biol. 2010, 120, 86–95.
  44. Chen, S.; Sims, G.P.; Chen, X.X.; Gu, Y.Y.; Chen, S.; Lipsky, P.E. Modulatory Effects of 1,25-Dihydroxyvitamin D3 on Human B Cell Differentiation. J. Immunol. 2007, 179, 1634–1647.
  45. Sassi, F.; Tamone, C.; D’Amelio, P. Vitamin D: Nutrient, Hormone, and Immunomodulator. Nutrients 2018, 10, 1656.
  46. Munns, C.F.; Shaw, N.; Kiely, M.; Specker, B.L.; Thacher, T.D.; Ozono, K.; Michigami, T.; Tiosano, D.; Mughal, M.Z.; Mäkitie, O.; et al. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. J. Clin. Endocrinol. Metab. 2016, 101, 394–415.
  47. Singal, A.G.; Higgins, P.D.R.; Waljee, A.K. A Primer on Effectiveness and Efficacy Trials. Clin. Transl. Gastroenterol. 2014, 5, e45.
  48. Perrine, C.G.; Sharma, A.J.; Jefferds, M.E.D.; Serdula, M.K.; Scanlon, K.S. Adherence to Vitamin D Recommendations among US Infants. Pediatrics 2010, 125, 627–632.
  49. Hemmingway, A.; Fisher, D.; Berkery, T.; Murray, D.M.; Kiely, M.E. Adherence to the Infant Vitamin D Supplementation Policy in Ireland. Eur. J. Nutr. 2021, 60, 1337–1345.
  50. Koc, F.; Halicioglu, O.; Sutcuoglu, S.; Asik Akman, S.; Aksit, S. Vitamin D Supplementation during the First Two Years of Life in Izmir, Turkey. Minerva Pediatr. 2014, 66, 141–146.
  51. Stoutjesdijk, E.; Schaafsma, A.; Kema, I.P.; van der Molen, J.; Dijck-Brouwer, D.A.J.; Muskiet, F.A.J. Influence of Daily 10–85 Μg Vitamin D Supplements during Pregnancy and Lactation on Maternal Vitamin D Status and Mature Milk Antirachitic Activity. Br. J. Nutr. 2019, 121, 426–438.
  52. Milani, G.P.; Simonetti, G.D.; Edefonti, V.; Lava, S.A.G.; Agostoni, C.; Curti, M.; Stettbacher, A.; Bianchetti, M.G.; Muggli, F. Seasonal Variability of the Vitamin D Effect on Physical Fitness in Adolescents. Sci. Rep. 2021, 11, 182.
  53. Rabufetti, A.; Milani, G.P.; Lava, S.A.G.; Edefonti, V.; Bianchetti, M.G.; Stettbacher, A.; Muggli, F.; Simonetti, G. Vitamin D Status Among Male Late Adolescents Living in Southern Switzerland: Role of Body Composition and Lifestyle. Nutrients 2019, 11, 2727.
  54. Bendik, I.; Friedel, A.; Roos, F.F.; Weber, P.; Eggersdorfer, M. Vitamin D: A Critical and Essential Micronutrient for Human Health. Front. Physiol. 2014, 5, 248.
  55. Pilz, S.; Zittermann, A.; Obeid, R.; Hahn, A.; Pludowski, P.; Trummer, C.; Lerchbaum, E.; Pérez-López, F.R.; Karras, S.N.; März, W. The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data. Int. J. Environ. Res. Public Health 2018, 15, 2241.
  56. Bae, Y.J.; Kratzsch, J. Vitamin D and Calcium in the Human Breast Milk. Best Pract. Res. Clin. Endocrinol. Metab. 2018, 32, 39–45.
  57. Wagner, C.L.; Taylor, S.N.; Johnson, D.D.; Hollis, B.W. The Role of Vitamin D in Pregnancy and Lactation: Emerging Concepts. Women’s Health 2012, 8, 323–340.
  58. Kiely, M.; O’Donovan, S.M.; Kenny, L.C.; Hourihane, J.O.; Irvine, A.D.; Murray, D.M. Vitamin D Metabolite Concentrations in Umbilical Cord Blood Serum and Associations with Clinical Characteristics in a Large Prospective Mother-Infant Cohort in Ireland. J. Steroid Biochem. Mol. Biol. 2017, 167, 162–168.
  59. Treiber, M.; Mujezinović, F.; Pečovnik Balon, B.; Gorenjak, M.; Maver, U.; Dovnik, A. Association between Umbilical Cord Vitamin D Levels and Adverse Neonatal Outcomes. J. Int. Med. Res. 2020, 48, 300060520955001.
  60. Braegger, C.; Campoy, C.; Colomb, V.; Decsi, T.; Domellof, M.; Fewtrell, M.; Hojsak, I.; Mihatsch, W.; Molgaard, C.; Shamir, R.; et al. Vitamin D in the Healthy European Paediatric Population. J. Pediatr. Gastroenterol. Nutr. 2013, 56, 692–701.
  61. Wagner, C.L.; Greer, F.R. Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents. Pediatrics 2008, 122, 1142–1152.
  62. Roth, D.E. What Should I Say to Parents about Vitamin D Supplementation from Infancy to Adolescence? Paediatr. Child Health 2009, 14, 575–577.
  63. Houghton, L.A.; Gray, A.R.; Szymlek-Gay, E.A.; Heath, A.-L.M.; Ferguson, E.L. Vitamin D-Fortified Milk Achieves the Targeted Serum 25-Hydroxyvitamin D Concentration without Affecting That of Parathyroid Hormone in New Zealand Toddlers. J. Nutr. 2011, 141, 1840–1846.
  64. Akkermans, M.D.; Eussen, S.R.; van der Horst-Graat, J.M.; van Elburg, R.M.; van Goudoever, J.B.; Brus, F. A Micronutrient-Fortified Young-Child Formula Improves the Iron and Vitamin D Status of Healthy Young European Children: A Randomized, Double-Blind Controlled Trial. Am. J. Clin. Nutr. 2017, 105, 391–399.
  65. Madsen, K.H.; Rasmussen, L.B.; Andersen, R.; Mølgaard, C.; Jakobsen, J.; Bjerrum, P.J.; Andersen, E.W.; Mejborn, H.; Tetens, I. Randomized Controlled Trial of the Effects of Vitamin D–Fortified Milk and Bread on Serum 25-Hydroxyvitamin D Concentrations in Families in Denmark during Winter: The VitmaD Study. Am. J. Clin. Nutr. 2013, 98, 374–382.
  66. Hower, J.; Knoll, A.; Ritzenthaler, K.L.; Steiner, C.; Berwind, R. Vitamin D Fortification of Growing up Milk Prevents Decrease of Serum 25-Hydroxyvitamin D Concentrations during Winter: A Clinical Intervention Study in Germany. Eur. J. Pediatr. 2013, 172, 1597–1605.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Academic Video Service
Feedback