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http://dx.doi.org/10.4162/nrp.2020.14.1.12

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)
Publication Information
Nutrition Research and Practice / v.14, no.1, 2020 , pp. 12-19 More about this Journal
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
Vitamin D; pediatrics;
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1 Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated Pediatric Risk of Mortality score. Crit Care Med 1996;24:743-52.   DOI
2 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.   DOI
3 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.   DOI
4 Rippel C, South M, Butt WW, Shekerdemian LS. Vitamin D status in critically ill children. Intensive Care Med 2012;38:2055-62.   DOI
5 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.   DOI
6 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.   DOI
7 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.   DOI
8 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.   DOI
9 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.   DOI
10 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.
11 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.   DOI
12 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.   DOI
13 Mostafa WZ, Hegazy RA. Vitamin D and the skin: focus on a complex relationship: a review. J Adv Res 2015;6:793-804.   DOI
14 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.
15 Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008;88:582S-6S.   DOI
16 Abou-Zahr R, Kandil SB. A pediatric critical care perspective on vitamin D. Pediatr Res 2015;77:164-7.   DOI
17 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.   DOI
18 Iruzubieta P, Teran A, Crespo J, Fabrega E. Vitamin D deficiency in chronic liver disease. World J Hepatol 2014;6:901-15.   DOI
19 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.   DOI
20 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.
21 Walker VP, Modlin RL. The vitamin D connection to pediatric infections and immune function. Pediatr Res 2009;65:106R-113R.   DOI
22 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.   DOI
23 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.   DOI
24 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.   DOI
25 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.   DOI
26 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.   DOI
27 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.   DOI
28 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.   DOI
29 Kaur G, Singh J, Kumar J. Vitamin D and cardiovascular disease in chronic kidney disease. Pediatr Nephrol. Forthcoming 2018.
30 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.
31 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.   DOI
32 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.   DOI
33 Koven NS, Cadden MH, Murali S, Ross MK. Vitamin D and long-term memory in multiple sclerosis. Cogn Behav Neurol 2013;26:155-60.   DOI
34 Lee JY, So TY, Thackray J. A review on vitamin d deficiency treatment in pediatric patients. J Pediatr Pharmacol Ther 2013;18: 277-91.   DOI
35 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.   DOI
36 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.   DOI
37 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.   DOI
38 Targher G, Pichiri I, Lippi G. Vitamin D, thrombosis, and hemostasis: more than skin deep. Semin Thromb Hemost 2012;38:114-24.   DOI
39 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.   DOI
40 Kim SY. The pleiomorphic actions of vitamin D and its importance for children. Ann Pediatr Endocrinol Metab 2013;18:45-54.   DOI
41 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.   DOI
42 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.
43 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.   DOI
44 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.   DOI
45 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.   DOI
46 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.   DOI
47 Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.   DOI
48 Massey K, Dickerson R, Brown R. A review of vitamin D deficiency in the critical care population. Pharmacy 2014;2:40-9.   DOI
49 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.   DOI
50 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.   DOI
51 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.   DOI
52 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.   DOI
53 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.   DOI