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J Pediatr Intensive Care 2016; 05(04): 142-153
DOI: 10.1055/s-0036-1583285
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Vitamin D Deficiency in Pediatric Critical Care

J. Dayre McNally
1   Division of Critical Care, Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada
2   Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Canada
,
Karin Amrein
3   Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Austria
› Author Affiliations
Further Information

Publication History

30 September 2015

22 October 2015

Publication Date:
04 May 2016 (online)

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Abstract

Vitamin D deficiency (VDD) is a well-established cause of pediatric bone and muscle disease. In addition, a role has been recognized for vitamin D in the health and stress response of other organs, including the cardiovascular, immune, and respiratory systems. As these organs are central to the development of and recovery from critical illness, VDD has been hypothesized to be a modifiable risk factor for ICU outcome. Over the past 5 years, a growing number of adult and pediatric critical care studies have investigated the prevalence of VDD and its association with illness severity and outcome. The adult studies have recently been synthesized in systematic reviews, with results that convincingly suggest the need for trials to determine whether optimization of vitamin D status improves outcome. In contrast, the pediatric ICU and related literature has not been similarly synthesized. The goal of this review is to describe vitamin D metabolism, known biological mechanisms, potential role in pathophysiology, and summarize the available pediatric intensive care unit (PICU) studies reporting on prevalence of VDD deficiency and its association with outcome. The problems with currently approved supplementation approaches and alternative strategies are discussed, including evidence from available RCTs in adult ICU. Altogether the results suggest that critically ill children are at risk for VDD, and that VDD appears to be associated with a worse clinical course. Clinical trials evaluating novel approaches to testing for and supplementing vitamin D require exploration.

Keywords

pediatric critical care - endocrinology - vitamin D
 

  • References

  • 1 Ward LM, Gaboury I, Ladhani M, Zlotkin S. Vitamin D-deficiency rickets among children in Canada. CMAJ 2007; 177 (2) 161-166
    CrossrefPubMedGoogle Scholar
  • 2 Mehrotra P, Marwaha RK, Aneja S , et al. Hypovitaminosis d and hypocalcemic seizures in infancy. Indian Pediatr 2010; 47 (7) 581-586
    CrossrefPubMedGoogle Scholar
  • 3 Basatemur E, Sutcliffe A. Incidence of hypocalcemic seizures due to vitamin D deficiency in children in the United Kingdom and Ireland. J Clin Endocrinol Metab 2015; 100 (1) E91-E95
    CrossrefPubMedGoogle Scholar
  • 4 Ginde AA, Mansbach JM, Camargo Jr CA. Vitamin D, respiratory infections, and asthma. [Review] [53 refs] Curr Allergy Asthma Rep 2009; 9 (1) 81-87
    CrossrefPubMedGoogle Scholar
  • 5 Kim SY. The pleiomorphic actions of vitamin D and its importance for children. Ann Pediatr Endocrinol Metab 2013; 18 (2) 45-54
    CrossrefPubMedGoogle Scholar
  • 6 Zittermann A, Gummert JF. Nonclassical vitamin D action. Nutrients 2010; 2 (4) 408-425
    CrossrefPubMedGoogle Scholar
  • 7 Lee P, Nair P, Eisman JA, Center JR. Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality?. Intensive Care Med 2009; 35 (12) 2028-2032
    CrossrefPubMedGoogle Scholar
  • 8 Youssef D, Amrein K, Schnedl C, Dobnig H, Peiris AN. Intensive Care and Vitamin D status. Diet and Nutrition in Critical Care. Vol 1. New York, NY: Springer; 2014: 16
    Google Scholar
  • 9 Amrein K, Venkatesh B. Vitamin D and the critically ill patient. Curr Opin Clin Nutr Metab Care 2012; 15 (2) 188-193
    CrossrefPubMedGoogle Scholar
  • 10 Christopher KB. Vitamin D supplementation in the ICU patient. Curr Opin Clin Nutr Metab Care 2015; 18 (2) 187-192
    CrossrefPubMedGoogle Scholar
  • 11 Lee P. Vitamin D metabolism and deficiency in critical illness. Best Pract Res Clin Endocrinol Metab 2011; 25 (5) 769-781
    CrossrefPubMedGoogle Scholar
  • 12 Amrein K, Christopher KB, McNally JD. Understanding vitamin D deficiency in intensive care patients. Intensive Care Med 2015; 41 (11) 1961-1964
    CrossrefPubMedGoogle Scholar
  • 13 Williams S, Heuberger R. Outcomes of vitamin D supplementation in adults who are deficient and critically ill: a review of the literature. Am J Ther 2015;
    PubMedGoogle Scholar
  • 14 Zajic P, Amrein K. Vitamin D deficiency in the ICU: a systematic review. Minerva Endocrinol 2014; 39 (4) 275-287
    PubMedGoogle Scholar
  • 15 de Haan K, Groeneveld AB, de Geus HR, Egal M, Struijs A. Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis. Crit Care 2014; 18 (6) 660
    CrossrefPubMedGoogle Scholar
  • 16 Zhang YP, Wan YD, Sun TW, Kan QC, Wang LX. Association between vitamin D deficiency and mortality in critically ill adult patients: a meta-analysis of cohort studies. Crit Care 2014; 18 (6) 684
    CrossrefPubMedGoogle Scholar
  • 17 Amrein K, Sourij H, Wagner G , et al. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care 2011; 15 (2) R104-R104
    CrossrefPubMedGoogle Scholar
  • 18 Mata-Granados JM, Vargas-Vasserot J, Ferreiro-Vera C, Luque de Castro MD, Pavón RG, Quesada Gómez JM. Evaluation of vitamin D endocrine system (VDES) status and response to treatment of patients in intensive care units (ICUs) using an on-line SPE-LC-MS/MS method. J Steroid Biochem Mol Biol 2010; 121 (1–2) 452-455
    CrossrefPubMedGoogle Scholar
  • 19 Nair P, Venkatesh B, Lee P , et al. A randomized study of a single dose of intramuscular cholecalciferol in critically ill adults. Crit Care Med 2015; 43 (11) 2313-2320
    CrossrefPubMedGoogle Scholar
  • 20 Dickerson RN, Berry SC, Ziebarth JD , et al. Dose-response effect of ergocalciferol therapy on serum 25-hydroxyvitamin D concentration during critical illness. Nutrition 2015; 31 (10) 1219-1223
    CrossrefPubMedGoogle Scholar
  • 21 Leaf DE, Raed A, Donnino MW, Ginde AA, Waikar SS. Randomized controlled trial of calcitriol in severe sepsis. Am J Respir Crit Care Med 2014; 190 (5) 533-541
    CrossrefPubMedGoogle Scholar
  • 22 Aminmansour B, Nikbakht H, Ghorbani A , et al. Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury: a randomized clinical trial with placebo group. Adv Biomed Res 2012; 1: 58
    CrossrefPubMedGoogle Scholar
  • 23 Amrein K, Schnedl C, Holl A , et al. Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. JAMA 2014; 312 (15) 1520-1530
    CrossrefPubMedGoogle Scholar
  • 24 Abou-Zahr R, Kandil SB. A pediatric critical care perspective on vitamin D. Pediatr Res 2015; 77 (1–2) 164-167
    CrossrefPubMedGoogle Scholar
  • 25 Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med 2008; 359 (4) 391-403
    CrossrefPubMedGoogle Scholar
  • 26 Nibbelink KA, Tishkoff DX, Hershey SD, Rahman A, Simpson RU. 1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization, in the HL-1 cardiac myocyte. J Steroid Biochem Mol Biol 2007; 103 (3–5) 533-537
    CrossrefPubMedGoogle Scholar
  • 27 Haussler MR, Jurutka PW, Mizwicki M, Norman AW. Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2 vitamin D3: genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab 2011; 25 (4) 543-559
    CrossrefPubMedGoogle Scholar
  • 28 Green JJ, Robinson DA, Wilson GE, Simpson RU, Westfall MV. Calcitriol modulation of cardiac contractile performance via protein kinase C. J Mol Cell Cardiol 2006; 41 (2) 350-359
    CrossrefPubMedGoogle Scholar
  • 29 Santillán GE, Vazquez G, Boland RL. Activation of a beta-adrenergic-sensitive signal transduction pathway by the secosteroid hormone 1,25-(OH)2-vitamin D3 in chick heart. J Mol Cell Cardiol 1999; 31 (5) 1095-1104
    CrossrefPubMedGoogle Scholar
  • 30 Tishkoff DX, Nibbelink KA, Holmberg KH, Dandu L, Simpson RU. Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility. Endocrinology 2008; 149 (2) 558-564
    CrossrefPubMedGoogle Scholar
  • 31 Holick MF, Binkley NC, Bischoff-Ferrari HA , et al; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96 (7) 1911-1930
    CrossrefPubMedGoogle Scholar
  • 32 Wagner CL, Greer FR ; American Academy of Pediatrics Section on Breastfeeding; American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 2008; 122 (5) 1142-1152
    CrossrefPubMedGoogle Scholar
  • 33 Willett AM. Vitamin D status and its relationship with parathyroid hormone and bone mineral status in older adolescents. Proc Nutr Soc 2005; 64 (2) 193-203
    CrossrefPubMedGoogle Scholar
  • 34 Christensen MH, Lien EA, Hustad S, Almås B. Seasonal and age-related differences in serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone in patients from Western Norway. Scand J Clin Lab Invest 2010; 70 (4) 281-286
    CrossrefPubMedGoogle Scholar
  • 35 Docio S, Riancho JA, Pérez A, Olmos JM, Amado JA, González-Macías J. Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies?. J Bone Miner Res 1998; 13 (4) 544-548
    CrossrefPubMedGoogle Scholar
  • 36 Thacher TD, Fischer PR, Isichei CO, Pettifor JM. Early response to vitamin D2 in children with calcium deficiency rickets. J Pediatr 2006; 149 (6) 840-844
    CrossrefPubMedGoogle Scholar
  • 37 Lee P, Eisman JA, Center JR. Vitamin D deficiency in critically ill patients. N Engl J Med 2009; 360 (18) 1912-1914
    CrossrefPubMedGoogle Scholar
  • 38 Cardenas-Rivero N, Chernow B, Stoiko MA, Nussbaum SR, Todres ID. Hypocalcemia in critically ill children. J Pediatr 1989; 114 (6) 946-951
    CrossrefPubMedGoogle Scholar
  • 39 Gauthier B, Trachtman H, Di Carmine F , et al. Hypocalcemia and hypercalcitoninemia in critically ill children. Crit Care Med 1990; 18 (11) 1215-1219
    CrossrefPubMedGoogle Scholar
  • 40 Iqbal M, Rehmani R, Hijazi M, Abdulaziz A, Kashif S. Hypocalcemia in a Saudi intensive care unit. Ann Thorac Med 2008; 3 (2) 57-59
    CrossrefPubMedGoogle Scholar
  • 41 Dyke II PC, Yates AR, Cua CL , et al. Increased calcium supplementation is associated with morbidity and mortality in the infant postoperative cardiac patient. Pediatr Crit Care Med 2007; 8 (3) 254-257
    CrossrefPubMedGoogle Scholar
  • 42 Broner CW, Stidham GL, Westenkirchner DF, Tolley EA. Hypermagnesemia and hypocalcemia as predictors of high mortality in critically ill pediatric patients. Crit Care Med 1990; 18 (9) 921-928
    CrossrefPubMedGoogle Scholar
  • 43 Kozik DJ, Tweddell JS. Characterizing the inflammatory response to cardiopulmonary bypass in children. Ann Thorac Surg 2006; 81 (6) S2347-S2354
    CrossrefPubMedGoogle Scholar
  • 44 Jaggers J, Lawson JH. Coagulopathy and inflammation in neonatal heart surgery: mechanisms and strategies. Ann Thorac Surg 2006; 81 (6) S2360-S2366
    CrossrefPubMedGoogle Scholar
  • 45 Baeke F, Gysemans C, Korf H, Mathieu C. Vitamin D insufficiency: implications for the immune system. Pediatr Nephrol 2010; 25 (9) 1597-1606
    CrossrefPubMedGoogle Scholar
  • 46 Rigby WF, Denome S, Fanger MW. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA. J Clin Invest 1987; 79 (6) 1659-1664
    CrossrefPubMedGoogle Scholar
  • 47 Bhalla AK, Amento EP, Serog B, Glimcher LH. 1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol 1984; 133 (4) 1748-1754
    PubMedGoogle Scholar
  • 48 Hata TR, Kotol P, Jackson M , et al. Administration of oral vitamin D induces cathelicidin production in atopic individuals. J Allergy Clin Immunol 2008; 122 (4) 829-831
    CrossrefPubMedGoogle Scholar
  • 49 Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J 2005; 19 (9) 1067-1077
    CrossrefPubMedGoogle Scholar
  • 50 Jeng L, Yamshchikov AV, Judd SE , et al. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med 2009; 7: 28-28
    CrossrefPubMedGoogle Scholar
  • 51 Gombart AF, Bhan I, Borregaard N , et al. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis 2009; 48 (4) 418-424
    CrossrefPubMedGoogle Scholar
  • 52 Leaf DE, Croy HE, Abrahams SJ, Raed A, Waikar SS. Cathelicidin antimicrobial protein, vitamin D, and risk of death in critically ill patients. Crit Care 2015; 19: 80
    CrossrefPubMedGoogle Scholar
  • 53 McNally JD, Sampson M, Matheson LA, Hutton B, Little J. Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: a systematic review and meta-analysis. Pediatr Pulmonol 2014; 49 (8) 790-799
    CrossrefPubMedGoogle Scholar
  • 54 Brehm JM, Schuemann B, Fuhlbrigge AL , et al; Childhood Asthma Management Program Research Group. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol 2010; 126 (1) 52-8.e5
    CrossrefPubMedGoogle Scholar
  • 55 Maxwell CS, Carbone ET, Wood RJ. Better newborn vitamin D status lowers RSV-associated bronchiolitis in infants. Nutr Rev 2012; 70 (9) 548-552
    CrossrefPubMedGoogle Scholar
  • 56 Menon K, Ward RE, Lawson ML, Gaboury I, Hutchison JS, Hébert PC ; Canadian Critical Care Trials Group. A prospective multicenter study of adrenal function in critically ill children. Am J Respir Crit Care Med 2010; 182 (2) 246-251
    CrossrefPubMedGoogle Scholar
  • 57 Olgun H, Ceviz N, Ozkan B. A case of dilated cardiomyopathy due to nutritional vitamin D deficiency rickets. Turk J Pediatr 2003; 45 (2) 152-154
    PubMedGoogle Scholar
  • 58 Price DI, Stanford Jr LC, Braden DS, Ebeid MR, Smith JC. Hypocalcemic rickets: an unusual cause of dilated cardiomyopathy. Pediatr Cardiol 2003; 24 (5) 510-512
    CrossrefPubMedGoogle Scholar
  • 59 Verma S, Khadwal A, Chopra K, Rohit M, Singhi S. Hypocalcemia nutritional rickets: a curable cause of dilated cardiomyopathy. J Trop Pediatr 2011; 57 (2) 126-128
    CrossrefPubMedGoogle Scholar
  • 60 Maiya S, Sullivan I, Allgrove J , et al. Hypocalcaemia and vitamin D deficiency: an important, but preventable, cause of life-threatening infant heart failure. Heart 2008; 94 (5) 581-584
    CrossrefPubMedGoogle Scholar
  • 61 Uysal S, Kalayci AG, Baysal K. Cardiac functions in children with vitamin D deficiency rickets. Pediatr Cardiol 1999; 20 (4) 283-286
    CrossrefPubMedGoogle Scholar
  • 62 Shedeed SA. Vitamin D supplementation in infants with chronic congestive heart failure. Pediatr Cardiol 2012; 33 (5) 713-719
    CrossrefPubMedGoogle Scholar
  • 63 Banwell BL, Mildner RJ, Hassall AC, Becker LE, Vajsar J, Shemie SD. Muscle weakness in critically ill children. Neurology 2003; 61 (12) 1779-1782
    CrossrefPubMedGoogle Scholar
  • 64 Williams S, Horrocks IA, Ouvrier RA, Gillis J, Ryan MM. Critical illness polyneuropathy and myopathy in pediatric intensive care: a review. Pediatr Crit Care Med 2007; 8 (1) 18-22
    CrossrefPubMedGoogle Scholar
  • 65 Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. N Engl J Med 2014; 370 (17) 1626-1635
    CrossrefPubMedGoogle Scholar
  • 66 Batt J, dos Santos CC, Cameron JI, Herridge MS. Intensive care unit-acquired weakness: clinical phenotypes and molecular mechanisms. Am J Respir Crit Care Med 2013; 187 (3) 238-246
    CrossrefPubMedGoogle Scholar
  • 67 Al-Said YA, Al-Rached HS, Al-Qahtani HA, Jan MMS. Severe proximal myopathy with remarkable recovery after vitamin D treatment. Can J Neurol Sci 2009; 36 (3) 336-339
    CrossrefPubMedGoogle Scholar
  • 68 Al-Said YA, Al-Rached HS, Al-Qahtani HA, Jan MM. Severe proximal myopathy with remarkable recovery after vitamin D treatment. Can J Neurol Sci 2009; 36 (3) 336-339
    CrossrefPubMedGoogle Scholar
  • 69 Ward KA, Das G, Berry JL , et al. Vitamin D status and muscle function in post-menarchal adolescent girls. J Clin Endocrinol Metab 2009; 94 (2) 559-563
    CrossrefPubMedGoogle Scholar
  • 70 van der Heyden JJ, Verrips A, ter Laak HJ, Otten B, Fiselier T. Hypovitaminosis D-related myopathy in immigrant teenagers. Neuropediatrics 2004; 35 (5) 290-292
    Article in Thieme ConnectPubMedGoogle Scholar
  • 71 Torun E, Genç H, Gönüllü E, Akovalı B, Ozgen IT. The clinical and biochemical presentation of vitamin D deficiency and insufficiency in children and adolescents. J Pediatr Endocrinol Metab 2013; 26 (5–6) 469-475
    PubMedGoogle Scholar
  • 72 Hazell TJ, Gallo S, Berzina I, Vanstone CA, Rodd C, Weiler HA. Plasma 25-hydroxyvitamin D, more so than its epimer, has a linear relationship to leaner body composition across infancy in healthy term infants. Appl Physiol Nutr Metab 2014; 39 (10) 1137-1143
    CrossrefPubMedGoogle Scholar
  • 73 Gallo S, Comeau K, Vanstone C , et al. Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: a randomized trial. JAMA 2013; 309 (17) 1785-1792
    CrossrefPubMedGoogle Scholar
  • 74 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 (10) 981-988
    Google Scholar
  • 75 Gottschlich MM, Mayes T, Khoury J, Warden GD. Hypovitaminosis D in acutely injured pediatric burn patients. J Am Diet Assoc 2004; 104 (6) 931-941 , quiz 1031
    CrossrefPubMedGoogle Scholar
  • 76 McNally JD, Menon K, Chakraborty P , et al; Canadian Critical Care Trials Group. The association of vitamin D status with pediatric critical illness. Pediatrics 2012; 130 (3) 429-436
    CrossrefPubMedGoogle Scholar
  • 77 Rippel C, South M, Butt WW, Shekerdemian LS. Vitamin D status in critically ill children. Intensive Care Med 2012; 38 (12) 2055-2062
    CrossrefPubMedGoogle Scholar
  • 78 Madden K, Feldman HA, Smith EM , et al. Vitamin D deficiency in critically ill children. Pediatrics 2012; 130 (3) 421-428
    Google Scholar
  • 79 Rey C, Sánchez-Arango D, López-Herce J , et al. Vitamin D deficiency at pediatric intensive care admission. J Pediatr (Rio J) 2014; 90 (2) 135-142 (Versão em Português)
    Google Scholar
  • 80 Ayulo Jr M, Katyal Ch, Agarwal Ch , et al. The prevalence of vitamin D deficiency and its relationship with disease severity in an urban pediatric critical care unit. Endocr Regul 2014; 48 (2) 69-76
    CrossrefPubMedGoogle Scholar
  • 81 Hebbar KB, Wittkamp M, Alvarez JA, McCracken CE, Tangpricha V, Vitamin D. Vitamin D deficiency in pediatric critical illness. J Clin Transl Endocrinol 2014; 1 (4) 170-175
    Google Scholar
  • 82 Prasad S, Raj D, Warsi S, Chowdhary S, Vitamin D. Vitamin D deficiency and critical illness. Indian J Pediatr 2015; 82 (11) 991-995
    Google Scholar
  • 83 Onwuneme C, Carroll A, Doherty D , et al. Inadequate vitamin D levels are associated with culture positive sepsis and poor outcomes in paediatric intensive care. Acta Paediatr 2015; 104 (10) e433-e438
    CrossrefPubMedGoogle Scholar
  • 84 Ebenezer K, Job V, Antonisamy B, Dawodu A, Manivachagan MN, Steinhoff M. Serum vitamin D status and outcome among critically ill children admitted to the pediatric intensive care unit in South India. Indian J Pediatr 2015;
    PubMedGoogle Scholar
  • 85 Ponnarmeni S, Kumar Angurana S, Singhi S , et al. Vitamin D deficiency in critically ill children with sepsis. Paediatr Int Child Health 2016; 36 (1) 15-21
    Google Scholar
  • 86 McNally JD, Menon K, Chakraborty P , et al. Impact of anesthesia and surgery for congenital heart disease on the vitamin d status of infants and children: a prospective longitudinal study. Anesthesiology 2013; 119 (1) 71-80
    CrossrefPubMedGoogle Scholar
  • 87 Graham EM, Taylor SN, Zyblewski SC , et al. Vitamin D status in neonates undergoing cardiac operations: relationship to cardiopulmonary bypass and association with outcomes. J Pediatr 2013; 162 (4) 823-826
    CrossrefPubMedGoogle Scholar
  • 88 Gottschlich MM, Mayes T, Khoury J, Kagan RJ. Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients. JPEN J Parenter Enteral Nutr 2015;
    PubMedGoogle Scholar
  • 89 Dayal D, Kumar S, Sachdeva N, Kumar R, Singh M, Singhi S. Fall in vitamin D levels during hospitalization in children. Int J Pediatr 2014; 2014: 291856
    PubMedGoogle Scholar
  • 90 Higgins DM, Wischmeyer PE, Queensland KM, Sillau SH, Sufit AJ, Heyland DK. Relationship of vitamin D deficiency to clinical outcomes in critically ill patients. JPEN J Parenter Enteral Nutr 2012; 36 (6) 713-720
    CrossrefPubMedGoogle Scholar
  • 91 Yi HJ, Jeong JH, Jin ES, Shin IY, Hwang HS, Moon SM. Evaluation of vitamin D level in patients from neurosurgical intensive care unit. Neural Regen Res 2013; 8 (16) 1528-1534
    PubMedGoogle Scholar
  • 92 Lange N, Litonjua AA, Gibbons FK, Giovannucci E, Christopher KB. Pre-hospital vitamin D concentration, mortality, and bloodstream infection in a hospitalized patient population. Am J Med 2013; 126 (7) 640.e19-640.e27
    CrossrefPubMedGoogle Scholar
  • 93 Amrein K, Litonjua AA, Moromizato T , et al. Increases in pre-hospitalization serum 25(OH)D concentrations are associated with improved 30-day mortality after hospital admission: A cohort study. Clin Nutr 2015;
    PubMedGoogle Scholar
  • 94 Braun A, Chang D, Mahadevappa K , et al. Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill. Crit Care Med 2011; 39 (4) 671-677
    CrossrefPubMedGoogle Scholar
  • 95 Ross AC, Manson JE, Abrams SA , et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011; 96 (1) 53-58
    CrossrefPubMedGoogle Scholar
  • 96 Godel JC. Vitamin D supplementation: recommendations for Canadian mothers and infants. Paediatr Child Health (Oxford) 2007; 12 (7) 583-598
    PubMedGoogle Scholar
  • 97 Holmlund-Suila E, Viljakainen H, Hytinantti T, Lamberg-Allardt C, Andersson S, Mäkitie 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) 4139-4147
    CrossrefPubMedGoogle Scholar
  • 98 McNally JD, Iliriani K, Pojsupap S , et al. Rapid normalization of vitamin D levels: a meta-analysis. Pediatrics 2015; 135 (1) e152-e166
    CrossrefPubMedGoogle Scholar
  • 99 Manaseki-Holland S, Qader G, Isaq Masher M , et al. Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Trop Med Int Health 2010; 15 (10) 1148-1155
    CrossrefPubMedGoogle Scholar
  • 100 Pojsupap S, Iliriani K, Sampaio TZ , et al. Efficacy of high-dose vitamin D in pediatric asthma: a systematic review and meta-analysis. J Asthma 2014; 1-9
    PubMedGoogle Scholar
  • 101 Yadav M, Mittal K. Effect of vitamin D supplementation on moderate to severe bronchial asthma. Indian J Pediatr 2014; 81 (7) 650-654
    CrossrefPubMedGoogle Scholar
  • 102 Joshi R. Hypercalcemia due to hypervitaminosis D: report of seven patients. J Trop Pediatr 2009; 55 (6) 396-398
    CrossrefPubMedGoogle Scholar
  • 103 Markestad T, Hesse V, Siebenhuner M , et al. Intermittent high-dose vitamin D prophylaxis during infancy: effect on vitamin D metabolites, calcium, and phosphorus. Am J Clin Nutr 1987; 46 (4) 652-658
    CrossrefPubMedGoogle Scholar
  • 104 Lewis RD, Laing EM, Hill Gallant KM , et al. A randomized trial of vitamin D3 supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption. J Clin Endocrinol Metab 2013; 98 (12) 4816-4825
    CrossrefPubMedGoogle Scholar
  • 105 Ammenti A, Pelizzoni A, Cecconi M, Molinari PP, Montini G. Nephrocalcinosis in children: a retrospective multi-centre study. Acta Paediatr 2009; 98 (10) 1628-1631
    CrossrefPubMedGoogle Scholar
  • 106 Rönnefarth G, Misselwitz J. Nephrocalcinosis in children: a retrospective survey. Members of the Arbeitsgemeinschaft für pädiatrische Nephrologie. Pediatr Nephrol 2000; 14 (10–11) 1016-1021
    CrossrefPubMedGoogle Scholar
  • 107 Moncrieff MW, Chance GW. Nephrotoxic effect of vitamin D therapy in vitamin D refractory rickets. Arch Dis Child 1969; 44 (237) 571-579
    CrossrefPubMedGoogle Scholar
  • 108 Mantan M, Bagga A, Virdi VS, Menon S, Hari P. Etiology of nephrocalcinosis in northern Indian children. Pediatr Nephrol 2007; 22 (6) 829-833
    CrossrefPubMedGoogle Scholar
  • 109 Alon US. Nephrocalcinosis. Curr Opin Pediatr 1997; 9 (2) 160-165
    CrossrefPubMedGoogle Scholar
  • 110 Kosecik M, Ertas T. Dilated cardiomyopathy due to nutritional vitamin D deficiency rickets. Pediatr Int 2007; 49 (3) 397-399
    CrossrefPubMedGoogle Scholar
  • 111 Manaseki-Holland S, Maroof Z, Bruce J , et al. Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial. Lancet 2012; 379 (9824) 1419-1427
    CrossrefPubMedGoogle Scholar
  • 112 Quraishi SA, Bittner EA, Blum L, McCarthy CM, Bhan I, Camargo Jr CA. Prospective study of vitamin D status at initiation of care in critically ill surgical patients and risk of 90-day mortality. Crit Care Med 2014; 42 (6) 1365-1371
    CrossrefPubMedGoogle Scholar
  • 113 Nair P, Lee P, Reynolds C , et al. Significant perturbation of vitamin D-parathyroid-calcium axis and adverse clinical outcomes in critically ill patients. Intensive Care Med 2013; 39 (2) 267-274
    CrossrefPubMedGoogle Scholar
  • 114 Dayre McNally J, 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 (8) 2942-5
    CrossrefPubMedGoogle Scholar
  • 115 Madden K, Feldman HA, Chun RF , et al. Critically ill children have low vitamin d-binding protein, influencing bioavailability of vitamin D. Ann Am Thorac Soc 2015; 12 (11) 1654-1661
    PubMedGoogle Scholar