Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Association of vitamin D deficiency with clinical outcomes in critically ill Korean children

  • Jhang, Won Kyoung (Division of Pediatric Critical Care medicine, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Kim, Da Hyun (Division of Pediatric Critical Care medicine, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Park, Seong Jong (Division of Pediatric Critical Care medicine, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine)
  • Received : 2019.04.24
  • Accepted : 2019.08.02
  • Published : 2020.02.01
Download PDF
⟨ Previous Next ⟩

Abstract

BACKGROUND/OBJECTIVES: Vitamin D is a pleiotropic hormone that affects various body organ systems. We evaluated the prevalence of a vitamin D deficiency (VDD) and its potential role in the clinical condition of critically ill Korean children. SUBJECTS/METHODS: Patients under 18 years old with a 25(OH) vitamin D measurement on the first day of PICU admission were included from among the children admitted to the pediatric intensive care unit (PICU) of our tertiary children's hospital between October 2017 and January 2019. RESULTS: A total of 172 pediatric patients were enrolled. The mean 25(OH) vitamin D level was 17.5 ± 12.8 ng/mL. There was a 65.1% prevalence of VDD (25(OH) vitamin D level < 20 ng/mL). VDD was associated with age at PICU admission, gastrointestinal/hepatobiliary disorders, International Society of Thrombosis and Hemostasis disseminated intravascular coagulation (ISTH DIC) score, pediatric multiple organ dysfunction syndrome (pMODS) score and with several laboratory test findings including hemoglobin, platelet, C-reactive protein, serum albumin, total bilirubin, prothrombin time, and anti-thrombin III levels. Most of these parameters also showed significant linear correlations with the 25(OH) vitamin D level (P < 0.05). However, no statistically meaningful association was found between VDD and other clinical conditions such as the need for a mechanical ventilator, requirement for vasoactive drugs, duration of the PICU and hospital stays, or PICU mortality. CONCLUSION: There is a high prevalence of VDD in critically ill Korean children. There were significant associations between the 25(OH) vitamin D level and gastrointestinal/hepatobiliary disorders, the pMODS score and with coagulation related factors. Further large-scale studies with more specific subgroup analyses are required to more precisely assess the clinical implications of VDD in critically ill pediatric patients.

Keywords

References

  1. Kim SY. The pleiomorphic actions of vitamin D and its importance for children. Ann Pediatr Endocrinol Metab 2013;18:45-54. https://doi.org/10.6065/apem.2013.18.2.45
  2. Massey K, Dickerson R, Brown R. A review of vitamin D deficiency in the critical care population. Pharmacy 2014;2:40-9. https://doi.org/10.3390/pharmacy2010040
  3. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M; Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics 2008;122:398-417. https://doi.org/10.1542/peds.2007-1894
  4. Walker VP, Modlin RL. The vitamin D connection to pediatric infections and immune function. Pediatr Res 2009;65:106R-113R. https://doi.org/10.1203/PDR.0b013e31819dba91
  5. Banerjee A, Khemka VK. Augmentation of anticoagulant effect with vitamin D: possible therapeutic target for venous thromboembolism. Int J Hematol Blo Dis 2017;2:1-5. https://doi.org/10.15226/2639-7986/2/1/00106
  6. Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berl) 2010;88:441-50. https://doi.org/10.1007/s00109-010-0590-9
  7. Kaur G, Singh J, Kumar J. Vitamin D and cardiovascular disease in chronic kidney disease. Pediatr Nephrol. Forthcoming 2018.
  8. Hirschler V, Molinari C, Maccallini G, Intersimone P, Gonzalez CD. Vitamin D levels and cardiometabolic markers in indigenous argentinean children living at different altitudes. Glob Pediatr Health 2019;6:2333794X18821942.
  9. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004;79:362-71. https://doi.org/10.1093/ajcn/79.3.362
  10. Helou M, Ning Y, Yang S, Irvine P, Bachmann LM, Godder K, Massey G. Vitamin d deficiency in children with cancer. J Pediatr Hematol Oncol 2014;36:212-7. https://doi.org/10.1097/MPH.0b013e31829f3754
  11. McNally JD, Leis K, Matheson LA, Karuananyake C, Sankaran K, Rosenberg AM. Vitamin D deficiency in young children with severe acute lower respiratory infection. Pediatr Pulmonol 2009;44:981-8. https://doi.org/10.1002/ppul.21089
  12. Koven NS, Cadden MH, Murali S, Ross MK. Vitamin D and long-term memory in multiple sclerosis. Cogn Behav Neurol 2013;26:155-60. https://doi.org/10.1097/WNN.0000000000000009
  13. Braun AB, Gibbons FK, Litonjua AA, Giovannucci E, Christopher KB. Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality. Crit Care Med 2012;40:63-72. https://doi.org/10.1097/CCM.0b013e31822d74f3
  14. Amrein K, Zajic P, Schnedl C, Waltensdorfer A, Fruhwald S, Holl A, Purkart T, Wunsch G, Valentin T, Grisold A, Stojakovic T, Amrein S, Pieber TR, Dobnig H. Vitamin D status and its association with season, hospital and sepsis mortality in critical illness. Crit Care 2014;18:R47. https://doi.org/10.1186/cc13790
  15. Cecchi A, Bonizzoli M, Douar S, Mangini M, Paladini S, Gazzini B, Degl'Innocenti S, Linden M, Zagli G, Peris A. Vitamin D deficiency in septic patients at ICU admission is not a mortality predictor. Minerva Anestesiol 2011;77:1184-9.
  16. Sankar J, Lotha W, Ismail J, Anubhuti C, Meena RS, Sankar MJ. Vitamin D deficiency and length of pediatric intensive care unit stay: a prospective observational study. Ann Intensive Care 2016;6:3. https://doi.org/10.1186/s13613-015-0102-8
  17. Ponnarmeni S, Kumar Angurana S, Singhi S, Bansal A, Dayal D, Kaur R, Patial A, Verma Attri S. Vitamin D deficiency in critically ill children with sepsis. Paediatr Int Child Health 2016;36:15-21. https://doi.org/10.1179/2046905515y.0000000042
  18. McNally JD, Menon K, Lawson ML, Williams K, Doherty DR. 1,25-Dihydroxyvitamin D levels in pediatric intensive care units: risk factors and association with clinical course. J Clin Endocrinol Metab 2015;100:2942-5. https://doi.org/10.1210/jc.2014-4471
  19. Sankar J, Ismail J, Das R, Dev N, Chitkara A, Sankar MJ. Effect of severe vitamin D deficiency at admission on shock reversal in children with septic shock: a prospective observational study. J Intensive Care Med 2019;34:397-403. https://doi.org/10.1177/0885066617699802
  20. McNally JD, Nama N, O'Hearn K, Sampson M, Amrein K, Iliriani K, McIntyre L, Fergusson D, Menon K. Vitamin D deficiency in critically ill children: a systematic review and meta-analysis. Crit Care 2017;21:287. https://doi.org/10.1186/s13054-017-1875-y
  21. Becker P, Carney LN, Corkins MR, Monczka J, Smith E, Smith SE, Spear BA, White JV; Academy of Nutrition and Dietetics; American Society for Parenteral and Enteral Nutrition. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: indicators recommended for the identification and documentation of pediatric malnutrition (undernutrition). Nutr Clin Pract 2015;30:147-61. https://doi.org/10.1177/0884533614557642
  22. Mehta NM, Corkins MR, Lyman B, Malone A, Goday PS, Carney LN, Monczka JL, Plogsted SW, Schwenk WF; American Society for Parenteral and Enteral Nutrition Board of Directors. Defining pediatric malnutrition: a paradigm shift toward etiology-related definitions. JPEN J Parenter Enteral Nutr 2013;37:460-81. https://doi.org/10.1177/0148607113479972
  23. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81. https://doi.org/10.1056/NEJMra070553
  24. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-30. https://doi.org/10.1210/jc.2011-0385
  25. Rusinska A, Pludowski P, Walczak M, Borszewska-Kornacka MK, Bossowski A, Chlebna-Sokol D, Czech-Kowalska J, Dobrzanska A, Franek E, Helwich E, Jackowska T, Kalina MA, Konstantynowicz J, Ksiazyk J, Lewinski A, Lukaszkiewicz J, Marcinowska-Suchowierska E, Mazur A, Michalus I, Peregud-Pogorzelski J, Romanowska H, Ruchala M, Socha P, Szalecki M, Wielgos M, Zwolinska D, Zygmunt A. Vitamin D supplementation guidelines for general population and groups at risk of vitamin D deficiency in Poland-recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 update. Front Endocrinol (Lausanne) 2018;9:246. https://doi.org/10.3389/fendo.2018.00246
  26. Madden K, Feldman HA, Smith EM, Gordon CM, Keisling SM, Sullivan RM, Hollis BW, Agan AA, Randolph AG. Vitamin D deficiency in critically ill children. Pediatrics 2012;130:421-8. https://doi.org/10.1542/peds.2011-3328
  27. Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated Pediatric Risk of Mortality score. Crit Care Med 1996;24:743-52. https://doi.org/10.1097/00003246-199605000-00004
  28. Graciano AL, Balko JA, Rahn DS, Ahmad N, Giroir BP. The Pediatric Multiple Organ Dysfunction Score (P-MODS): development and validation of an objective scale to measure the severity of multiple organ dysfunction in critically ill children. Crit Care Med 2005;33:1484-91. https://doi.org/10.1097/01.CCM.0000170943.23633.47
  29. Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a pediatric sequential organ failure assessment score and evaluation of the sepsis-3 definitions in critically ill children. JAMA Pediatr 2017;171:e172352. https://doi.org/10.1001/jamapediatrics.2017.2352
  30. Rippel C, South M, Butt WW, Shekerdemian LS. Vitamin D status in critically ill children. Intensive Care Med 2012;38:2055-62. https://doi.org/10.1007/s00134-012-2718-6
  31. Mansbach JM, Ginde AA, Camargo CA Jr. Serum 25-hydroxyvitamin D levels among US children aged 1 to 11 years: do children need more vitamin D? Pediatrics 2009;124:1404-10. https://doi.org/10.1542/peds.2008-2041
  32. Levis S, Gomez A, Jimenez C, Veras L, Ma F, Lai S, Hollis B, Roos BA. Vitamin d deficiency and seasonal variation in an adult South Florida population. J Clin Endocrinol Metab 2005;90:1557-62. https://doi.org/10.1210/jc.2004-0746
  33. Hebbar KB, Wittkamp M, Alvarez JA, McCracken CE, Tangpricha V. Vitamin D deficiency in pediatric critical illness. J Clin Transl Endocrinol 2014;1:170-5. https://doi.org/10.1016/j.jcte.2014.09.002
  34. Kimlin MG, Lucas RM, Harrison SL, van der Mei I, Armstrong BK, Whiteman DC, Kricker A, Nowak M, Brodie AM, Sun J. The contributions of solar ultraviolet radiation exposure and other determinants to serum 25-hydroxyvitamin D concentrations in Australian adults: the AusD Study. Am J Epidemiol 2014;179:864-74. https://doi.org/10.1093/aje/kwt446
  35. Al-Othman A, Al-Musharaf S, Al-Daghri NM, Krishnaswamy S, Yusuf DS, Alkharfy KM, Al-Saleh Y, Al-Attas OS, Alokail MS, Moharram O, Sabico S, Chrousos GP. Effect of physical activity and sun exposure on vitamin D status of Saudi children and adolescents. BMC Pediatr 2012;12:92.
  36. Holick MF, Chen TC, Lu Z, Sauter E. Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res 2007;22 Suppl 2:V28-33. https://doi.org/10.1359/jbmr.07s211
  37. Weishaar T, Rajan S, Keller B. Probability of vitamin D deficiency by body weight and race/ethnicity. J Am Board Fam Med 2016;29:226-32. https://doi.org/10.3122/jabfm.2016.02.150251
  38. Mostafa WZ, Hegazy RA. Vitamin D and the skin: focus on a complex relationship: a review. J Adv Res 2015;6:793-804. https://doi.org/10.1016/j.jare.2014.01.011
  39. Newton DA, Baatz JE, Kindy MS, Gattoni-Celli S, Shary JR, Hollis BW, Wagner CL. Vitamin D binding protein polymorphisms significantly impact vitamin D status in children. Pediatr Res. Forthcoming 2019.
  40. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 2013;369:1991-2000. https://doi.org/10.1056/NEJMoa1306357
  41. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008;88:582S-6S. https://doi.org/10.1093/ajcn/88.2.582S
  42. Abou-Zahr R, Kandil SB. A pediatric critical care perspective on vitamin D. Pediatr Res 2015;77:164-7. https://doi.org/10.1038/pr.2014.167
  43. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 1986;63:954-9. https://doi.org/10.1210/jcem-63-4-954
  44. Iruzubieta P, Teran A, Crespo J, Fabrega E. Vitamin D deficiency in chronic liver disease. World J Hepatol 2014;6:901-15. https://doi.org/10.4254/wjh.v6.i12.901
  45. Langer-Gould A, Lucas RM, Xiang AH, Wu J, Chen LH, Gonzales E, Haraszti S, Smith JB, Quach H, Barcellos LF. Vitamin D-binding protein polymorphisms, 25-hydroxyvitamin D, sunshine and multiple sclerosis. Nutrients 2018;10:E184.
  46. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, Kiel DP, Streeten EA, Ohlsson C, Koller DL, Peltonen L, Cooper JD, O'Reilly PF, Houston DK, Glazer NL, Vandenput L, Peacock M, Shi J, Rivadeneira F, McCarthy MI, Anneli P, de Boer IH, Mangino M, Kato B, Smyth DJ, Booth SL, Jacques PF, Burke GL, Goodarzi M, Cheung CL, Wolf M, Rice K, Goltzman D, Hidiroglou N, Ladouceur M, Wareham NJ, Hocking LJ, Hart D, Arden NK, Cooper C, Malik S, Fraser WD, Hartikainen AL, Zhai G, Macdonald HM, Forouhi NG, Loos RJ, Reid DM, Hakim A, Dennison E, Liu Y, Power C, Stevens HE, Jaana L, Vasan RS, Soranzo N, Bojunga J, Psaty BM, Lorentzon M, Foroud T, Harris TB, Hofman A, Jansson JO, Cauley JA, Uitterlinden AG, Gibson Q, Jarvelin MR, Karasik D, Siscovick DS, Econs MJ, Kritchevsky SB, Florez JC, Todd JA, Dupuis J, Hypponen E, Spector TD. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 2010;376:180-8. https://doi.org/10.1016/S0140-6736(10)60588-0
  47. Bahrami A, Sadeghnia HR, Tabatabaeizadeh SA, Bahrami-Taghanaki H, Behboodi N, Esmaeili H, Ferns GA, Mobarhan MG, Avan A. Genetic and epigenetic factors influencing vitamin D status. J Cell Physiol 2018;233:4033-43. https://doi.org/10.1002/jcp.26216
  48. Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 2010;19:2739-45. https://doi.org/10.1093/hmg/ddq155
  49. Moy KA, Mondul AM, Zhang H, Weinstein SJ, Wheeler W, Chung CC, Mannisto S, Yu K, Chanock SJ, Albanes D. Genome-wide association study of circulating vitamin D-binding protein. Am J Clin Nutr 2014;99:1424-31. https://doi.org/10.3945/ajcn.113.080309
  50. Agmon-Levin N, Blank M, Zandman-Goddard G, Orbach H, Meroni PL, Tincani A, Doria A, Cervera R, Miesbach W, Stojanovich L, Barak V, Porat-Katz BS, Amital H, Shoenfeld Y. Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression. Ann Rheum Dis 2011;70:145-50. https://doi.org/10.1136/ard.2010.134817
  51. Targher G, Pichiri I, Lippi G. Vitamin D, thrombosis, and hemostasis: more than skin deep. Semin Thromb Hemost 2012;38:114-24. https://doi.org/10.1055/s-0031-1300957
  52. Elbers LP, Wijnberge M, Meijers JC, Poland DC, Brandjes DP, Fliers E, Gerdes VE. Coagulation and fibrinolysis in hyperparathyroidism secondary to vitamin D deficiency. Endocr Connect 2018;7:325-33. https://doi.org/10.1530/EC-17-0249
  53. Lee JY, So TY, Thackray J. A review on vitamin d deficiency treatment in pediatric patients. J Pediatr Pharmacol Ther 2013;18: 277-91. https://doi.org/10.5863/1551-6776-18.4.277

Cited by

  1. Vitamin D deficiency relation to sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill childre vol.75, pp.4, 2020, https://doi.org/10.1111/ijcp.13908