Systematic Review with Meta Analysis Vitamin D supplementation for the prevention of childhood acute respiratory infections: a systematic review of randomised controlled trials

Results from recent trials assessing the effect of vitamin D supplementation on the prevention of childhood acute respiratory infections (ARI) have been inconsistent. In the present study, we determined whether vitamin D supplementation prevents ARI in healthy children and repeated infections in children with previous ARI. We conducted a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The search included only randomised controlled clinical trials (RCT) comparing vitamin D supplementation with either placebo or no intervention in children younger than 18 years of age. We identified seven RCT and found that the summary estimates were not statistically significantly associated with a reduction in the risk of ARI (relative risk (RR) 0·79, 95% CI 0·55, 1·13), all-cause mortality (RR 1·18, 95% CI 0·71, 1·94), or the rate of hospital admission due to respiratory infection in healthy children (RR 0·95, 95% CI 0·72, 1·26). However, in children previously diagnosed with asthma, vitamin D supplementation resulted in a 74% reduction in the risk of asthma exacerbation (RR 0·26, 95% CI 0·11, 0·59; test of heterogeneity, I 2 ¼ 0·0%). Our findings indicate a lack of evidence supporting the routine use of vitamin D supplementation for the prevention of ARI in healthy children; however, they suggest that such supplementation may benefit children previously diagnosed with asthma. Due to the heterogeneity of the included studies and possible publication biases related to this field, these results should be interpreted with caution.

[1]  M. Loeb,et al.  DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial , 2014, BMC Pediatrics.

[2]  C. Camargo,et al.  Vitamin D Status and Community-Acquired Pneumonia: Results from the Third National Health and Nutrition Examination Survey , 2013, PloS one.

[3]  A. Ginde,et al.  The role of vitamin D in prevention and treatment of infection. , 2013, Inflammation & allergy drug targets.

[4]  David A. Jolliffe,et al.  Vitamin D in the prevention of acute respiratory infection: Systematic review of clinical studies , 2013, The Journal of Steroid Biochemistry and Molecular Biology.

[5]  J. Lindh,et al.  Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials , 2013, PloS one.

[6]  M. Lucero,et al.  Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis , 2013, The Lancet.

[7]  S. Esposito,et al.  Role of Vitamin D in Children with Respiratory Tract Infection , 2013, International Journal of Immunopathology and Pharmacology.

[8]  C. Camargo,et al.  Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia , 2012, Pediatrics.

[9]  R. Heaney Vitamin D--baseline status and effective dose. , 2012, The New England journal of medicine.

[10]  Jamie Perin,et al.  Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000 , 2012, The Lancet.

[11]  N. Choudhary,et al.  Vitamin D supplementation for severe pneumonia — A randomized controlled trial , 2012, Indian Pediatrics.

[12]  Z. Bhutta,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 , 2012, The Lancet.

[13]  A. Martineau Bolus-dose vitamin D and prevention of childhood pneumonia , 2012, The Lancet.

[14]  B. Hollis Short-term and long-term consequences and concerns regarding valid assessment of vitamin D deficiency: comparison of recent food supplementation and clinical guidance reports , 2011, Current opinion in clinical nutrition and metabolic care.

[15]  A. Bar-Or,et al.  Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. , 2011, The Journal of clinical endocrinology and metabolism.

[16]  H. Sachdev,et al.  Effect of weekly vitamin D supplements on mortality, morbidity, and growth of low birthweight term infants in India up to age 6 months: randomised controlled trial , 2011, BMJ : British Medical Journal.

[17]  K. Smejda,et al.  Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. , 2011, The Journal of allergy and clinical immunology.

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

[19]  D. Chandramohan,et al.  Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial , 2010, Archives of Disease in Childhood.

[20]  R. Black,et al.  Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh , 2010, Acta paediatrica.

[21]  E. Goncharova,et al.  Vitamin D inhibits growth of human airway smooth muscle cells through growth factor‐induced phosphorylation of retinoblastoma protein and checkpoint kinase 1 , 2009, British journal of pharmacology.

[22]  Peter R Ebeling,et al.  Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  A. Auvinen,et al.  An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. , 2007, The American journal of clinical nutrition.

[24]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[25]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[26]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[27]  T. Oppé,et al.  Vitamin D deficiency. , 1979, British medical journal.

[28]  W. G. Cochran The combination of estimates from different experiments. , 1954 .

[29]  C. Brightling,et al.  Targeting TNF-α: A novel therapeutic approach for asthma , 2008 .

[30]  S Greenland,et al.  Quantitative methods in the review of epidemiologic literature. , 1987, Epidemiologic reviews.