Vitamin D Deficiency in Critically Ill Children

OBJECTIVE: Vitamin D influences cardiovascular and immune function. We aimed to establish the prevalence of vitamin D deficiency in critically ill children and identify factors influencing admission 25-hydroxy vitamin D (25(OH)D) levels. We hypothesized that levels would be lower with increased illness severity and in children with serious infections. METHODS: Participants were 511 severely or critically ill children admitted to the PICU from November 2009 to November 2010. Blood was collected near PICU admission and analyzed for 25(OH)D concentration by using Diasorin radioimmunoassay. RESULTS: We enrolled 511 of 818 (62.5%) eligible children. The median 25(OH)D level was 22.5 ng/mL; 40.1% were 25(OH)D deficient (level <20 ng/mL). In multivariate analysis, age and race were associated with 25(OH)D deficiency; summer season, vitamin D supplementation, and formula intake were protective; 25(OH)D levels were not lower in the 238 children (46.6%) admitted with a life-threatening infection, unless they had septic shock (n = 51, 10.0%) (median 25(OH)D level 19.2 ng/mL; P = .0008). After adjusting for factors associated with deficiency, lower levels were associated with higher admission day illness severity (odds ratio 1.19 for a 1-quartile increase in Pediatric Risk of Mortality III score per 5 ng/mL decrease in 25(OH)D, 95% confidence interval 1.10–1.28; P < .0001). CONCLUSIONS: We found a high rate of vitamin D deficiency in critically ill children. Given the roles of vitamin D in bone development and immunity, we recommend screening of those critically ill children with risk factors for vitamin D deficiency and implementation of effective repletion strategies.

[1]  S. Plein,et al.  Serum 25 hydroxy-vitamin D does not exhibit an acute phase reaction after acute myocardial infarction , 2012, Annals of clinical biochemistry.

[2]  E. Giovannucci,et al.  Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality* , 2012, Critical care medicine.

[3]  C. Wagner,et al.  Vitamin D supplementation during pregnancy: Double‐blind, randomized clinical trial of safety and effectiveness , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  C. Camargo,et al.  Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection. , 2011, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[5]  D. Talwar,et al.  The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. , 2011, The American journal of clinical nutrition.

[6]  E. Giovannucci,et al.  Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill* , 2011, Critical care medicine.

[7]  B. Bailey,et al.  Relationship between vitamin D status and ICU outcomes in veterans. , 2011, Journal of the American Medical Directors Association.

[8]  P. Hopkins,et al.  25-Hydroxyvitamin D is associated with plasma renin activity and the pressor response to dietary sodium intake in Caucasians , 2011, Journal of the renin-angiotensin-aldosterone system : JRAAS.

[9]  G. Pierce,et al.  25-Hydroxyvitamin D Deficiency Is Associated With Inflammation-Linked Vascular Endothelial Dysfunction in Middle-Aged and Older Adults , 2011, Hypertension.

[10]  JoAnn E. Manson,et al.  The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know , 2010, The Journal of clinical endocrinology and metabolism.

[11]  A. Krishnan,et al.  Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients , 2010, Critical care.

[12]  Faisel Yunus,et al.  Statistics Using SPSS: An Integrative Approach, second edition , 2010 .

[13]  M. Urashima,et al.  Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. , 2010, The American journal of clinical nutrition.

[14]  O. Lucidarme,et al.  Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study , 2010, Intensive Care Medicine.

[15]  H. Bauchner,et al.  Widespread Vitamin D Deficiency in Urban Massachusetts Newborns and Their Mothers , 2010, Pediatrics.

[16]  J. Eisman,et al.  Vitamin D deficiency in critically ill patients. , 2009, The New England journal of medicine.

[17]  C. Camargo,et al.  Serum 25-Hydroxyvitamin D Levels Among US Children Aged 1 to 11 Years: Do Children Need More Vitamin D? , 2009, Pediatrics.

[18]  A. Rosenberg,et al.  Vitamin D deficiency in young children with severe acute lower respiratory infection , 2009, Pediatric pulmonology.

[19]  S. Judd,et al.  Vitamin D Deficiency and Risk for Cardiovascular Disease , 2009, The American journal of the medical sciences.

[20]  R. Modlin,et al.  The Vitamin D Connection to Pediatric Infections and Immune Function , 2009, Pediatric Research.

[21]  G. Martin,et al.  Journal of Translational Medicine BioMed Central Review , 2008 .

[22]  R. Daynes,et al.  TLR-Induced Local Metabolism of Vitamin D3 Plays an Important Role in the Diversification of Adaptive Immune Responses1 , 2009, The Journal of Immunology.

[23]  P. Harris,et al.  Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support , 2009, J. Biomed. Informatics.

[24]  H. Bang,et al.  Implications of a New Definition of Vitamin D Deficiency in a Multiracial US Adolescent Population: The National Health and Nutrition Examination Survey III , 2009, Pediatrics.

[25]  C. Camargo,et al.  Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. , 2009, Archives of internal medicine.

[26]  D. Whellan,et al.  Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). , 2008, The American journal of cardiology.

[27]  C. Wagner,et al.  Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents , 2008, Pediatrics.

[28]  M. Misra,et al.  Vitamin D Deficiency in Children and Its Management: Review of Current Knowledge and Recommendations , 2008, Pediatrics.

[29]  Jeannette M. Perez-Rossello,et al.  Prevalence of vitamin D deficiency among healthy infants and toddlers. , 2008, Archives of pediatrics & adolescent medicine.

[30]  John H. White.  Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity , 2008, Infection and Immunity.

[31]  Michael J. Pencina,et al.  Vitamin D Deficiency and Risk of Cardiovascular Disease , 2008, Circulation.

[32]  Sharon L. Weinberg,et al.  Statistics Using IBM SPSS: An Integrative Approach , 2008 .

[33]  C. Gordon,et al.  Vitamin D deficiency in children and adolescents: Epidemiology, impact and treatment , 2008, Reviews in Endocrine and Metabolic Disorders.

[34]  R. Modlin,et al.  Cutting Edge: Vitamin D-Mediated Human Antimicrobial Activity against Mycobacterium tuberculosis Is Dependent on the Induction of Cathelicidin1 , 2007, The Journal of Immunology.

[35]  M. Pradeep Kumar,et al.  Modifiable risk factors for acute lower respiratory tract infections , 2007, Indian journal of pediatrics.

[36]  M. Holick.  Resurrection of vitamin D deficiency and rickets. , 2006, The Journal of clinical investigation.

[37]  J. Adams,et al.  Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response , 2006, Science.

[38]  T. Siddiqui,et al.  Presentation and predisposing factors of nutritional rickets in children of Hazara Division. , 2005, Journal of Ayub Medical College, Abbottabad : JAMC.

[39]  H. Koeffler,et al.  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 , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[40]  Naeema Afzal,et al.  An index of depression in patients with chronic nonspecific musculoskeletal pain. , 2005, Journal of Ayub Medical College, Abbottabad : JAMC.

[41]  H. Jha,et al.  Novel tempeh (fermented soyabean) isoflavones inhibit in vivo angiogenesis in the chicken chorioallantoic membrane assay , 2005, British Journal of Nutrition.

[42]  B. Hollis.  Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. , 2005, The Journal of nutrition.

[43]  S. Emans,et al.  Prevalence of vitamin D deficiency among healthy adolescents. , 2004, Archives of pediatrics & adolescent medicine.

[44]  S. Filteau,et al.  Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y , 2004, European Journal of Clinical Nutrition.

[45]  S. Filteau,et al.  Plasma 25-hydroxyvitamin D does not vary over the course of a malarial infection. , 2003, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[46]  G. Van den Berghe,et al.  Bone turnover in prolonged critical illness: effect of vitamin D , 2003, The Journal of clinical endocrinology and metabolism.

[47]  H. Minne,et al.  Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. , 2001, The Journal of clinical endocrinology and metabolism.

[48]  C. Sprung,et al.  Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. , 1998, Critical care medicine.

[49]  U. Ruttimann,et al.  PRISM III: an updated Pediatric Risk of Mortality score. , 1996, Critical care medicine.

[50]  Christine L. Taylor,et al.  Committee to Review Dietary Reference Intakes for Vitamin D and Calcium , 2011 .

[51]  C. Camargo,et al.  Vitamin D, respiratory infections, and asthma , 2009, Current allergy and asthma reports.