Vitamin D supplementation for preventing infections in children under five years of age

Abstract

Background Vitamin D is a micronutrient important for bone growth and immune function. Deficiency can lead to rickets and has been linked to various infections, including respiratory infections. The evidence on the effects of supplementation on infections in children has not been assessed systematically. Objectives To evaluate the role of vitamin D supplementation in preventing pneumonia, tuberculosis (TB), diarrhoea, and malaria in children under five years of age. This includes high‐, middle‐, and low‐income countries. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, MEDLINE, EMBASE, LILACS, the WHO International Clinical Trials Registry Platform (ICTRP; ) , ClinicalTrials.gov and the ISRCTN registry (http://www.isrctn.com/) up to 16 June 2016. Selection criteria We included randomized controlled trials (RCTs) that evaluated preventive supplementation of vitamin D (versus placebo or no intervention) in children under five years of age. Data collection and analysis Two review authors independently screened the titles and abstracts, extracted the data, and assessed the risk of bias of included trials. Main results Four trials met the inclusion criteria, with a total of 3198 children under five years of age, and were conducted in Afghanistan, Spain, and the USA. Prevalence of vitamin D deficiency varied widely in these populations (range: 73.1% in Afghanistan, 10 to 12% in USA, and 6.2% in Spain). The included trials evaluated mortality (two trials), pneumonia incidence (two trials), diarrhoea incidence (two trials), hospitalization (two trials), and mean serum vitamin D concentrations (four trials). We do not know whether vitamin D supplementation impacts on all‐cause mortality because this outcome was underpowered due to few events (risk ratio (RR) 1.43, 95% confidence interval (CI) 0.54 to 3.74; one trial, 3046 participants, low quality evidence ). For pneumonia, episodes of 'radiologically confirmed' first or only episode of pneumonia were little different in the supplemented and unsupplemented group (Rate Ratio: 1.06, 95% confidence interval (CI) 0.89 to 1.26; two trials, 3134 participants, moderate quality evidence ), and similarly for children with confirmed or unconfirmed pneumonia (RR 0.95, 95% CI 0.87 to 1.04; one trial, 3046 participants). In these two trials there were no obvious differences between supplemented and unsupplemented children regarding episodes of diarrhoea. In the single large trial from Afghanistan, the trial authors reported that vitamin D supplementation was associated with an increase in repeat episodes of pneumonia confirmed by chest radiograph (RR 1.69, 95% CI 1.28 to 2.21; one t...

The Role of Vitamin D in the Immune System as a Pro-survival Molecule

“…The wide pleiotropism of this natural hormone vitamin, which can be considered similar to other diet-derived plant polyphenols, antioxidants, and additional nutritional supplements, 1 is disconcerting, compared with the high frequency of deficient levels of circulating vitamin D in the human population. [2][3][4][5] Despite its importance, people seem to live perfectly with apparently long-lasting deficiencies of vitamin D. Vitamin D is an ancient hormonal molecule; it is photosynthesized in all forms of life, starting from the phytoplankton ( 750 million years ago) to mammals and humans. 6 For certain aspects, vitamin D might be selected as one of the first natural antioxidant prohormones from nonplant-derived foods, and thus cells were instructed to synthesize it.…”

Vitamin D status is associated with treatment failure and duration of illness in Nepalese children with severe pneumonia

“…Different immunomodulatory effects may explain these associations (5). Moreover, despite convincing in vitro findings, there are examples of observational studies finding no associations (6), and clinical trials and reviews have been inconclusive about the role of vitamin D (7,8). These inconsistent findings have led to a discussion on whether hypovitaminosis D is a cause or a consequence of inflammation (9,10).…”

What do Cochrane systematic reviews say about interventions for vitamin D supplementation?

“…Among the preventive systematic reviews, five focused on healthy individuals for prevention of death, 16 cancer, 14 and other adverse outcomes. 12,25,27 Despite the considerable number of Cochrane reviews, eight of them did not present any reliable evidence regarding benefits or harm from vitamin D, including reviews on clinical situations in which use of vitamin D is frequently observed in clinical practice, such as in relation to multiple sclerosis 9 and atopic eczema. 7 Thus, in those reviews, the authors were unable to provide recommendations regarding the benefits and risks of vitamin D. A second point that deserves discussion is that many of the reviews included were planned, conducted or published some years ago, and therefore were based on early versions of the Cochrane Handbook, which were less detailed and complex than the current version (http:// training.cochrane.org/handbook).…”