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; http://www.who.int/ictrp/en/), 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 trial, 3046 participants), but not reflected in the outcome of confirmed or unconfirmed pneumonia (RR 1.06, 95% CI 1.00 to 1.13; one trial, 3046 participants).

For hospital admission measured in one small trial, there was no difference detected (RR 0.86, 95% CI 0.20 to 3.62; one trial, 88 participants; very low quality evidence).

The mean serum vitamin D concentrations were higher in supplemented compared to unsupplemented children at the end of supplementation (MD 7.72 ng/mL, 95% CI 0.50 to 14.93; four trials, 266 participants, low quality evidence). These results were driven primarily by two smaller trials with large magnitudes of effect. In the other two bigger trials, serum vitamin D concentrations were elevated in the intervention group for most of the trial duration but not at the end of supplementation. This may be due to time elapsed at measurement from the last dose, incomplete compliance, or increased need of vitamin D with infant age.

We did not find any trial that reported on the incidence of TB, malaria or febrile illness, duration of pneumonia, duration of diarrhoea, severity of infection, and cause-specific mortality (due to TB, diarrhoea, or malaria).

Authors' conclusions

Evidence from one large trial did not demonstrate benefit of vitamin D supplementation on the incidence of pneumonia or diarrhoea in children under five years. To our knowledge, trials that evaluated supplementation for preventing other infections, including TB and malaria, have not been performed.

PLAIN LANGUAGE SUMMARY

Vitamin D supplementation for preventing infections in children under five

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. Several studies have reported an association between vitamin D deficiency and infections among children, and is thought to be related to the role of vitamin D in the immune system. In this systematic review, Cochrane researchers examined the role of vitamin D supplementation in prevention of infections in children under five years of age. The researchers studied the infections of pneumonia, tuberculosis (TB), diarrhoea, and malaria in this review.

Study characteristics

The review authors examined the available evidence up to 17 June 2016, and included four trials with a total of 3198 children under five years of age. The included trials were conducted in Afghanistan, Spain and the USA.

Key findings

The review did not detect an effect of vitamin D supplementation on death ( low quality evidence); the occurrence of the first or only episode of pneumonia; or on children with pneumonia, irrespective of whether this had been confirmed by hospital tests ( moderate quality evidence). Limited evidence showed that there was no obvious difference in the first or repeat episodes of diarrhoea between supplemented and unsupplemented children. We do not know about whether Vitamin D influences hospital admissions as there was only one small study measuring this ( very low quality evidence). The mean serum vitamin D concentrations were higher in the supplemented versus unsupplemented children at the end of supplementation period ( low quality evidence). One large trial from Afghanistan showed an increase in repeat episodes of confirmed pneumonia but not on confirmed and unconfirmed pneumonia. None of the included trials reported on TB or malaria as outcomes.

Conclusions

One large trial has not demonstrated an effect of vitamin D on death or respiratory infections in children under five years of age. We did not find trials evaluating Vitamin D supplementation to prevent other infections such as TB and malaria.