Is vitamin D an effective and safe addition to antibiotics to treat children with acute pneumonia?

Review question

We wanted to find out if vitamin D helps children with acute pneumonia who are also receiving antibiotic treatment get better faster.

Background

Pneumonia is an acute lower respiratory tract infection that affects the lungs. Treatment for pneumonia includes antibiotics, providing supplementary oxygen to air that is breathed in through a mask, and other supportive therapies. Vitamin D boosts immune defences and reduces excessive inflammation, effects that may help children recover from an acute episode of pneumonia.

Search date

The evidence is current to 28 July 2017.

Study characteristics

We included seven studies involving a total of 1529 children (780 with pneumonia (4 studies) and 749 with severe or very severe pneumonia (3 studies)) aged under 5 years from low-income countries. In four studies, a single large dose of vitamin D was used either when the child joined the study or within 24 hours of admission to hospital; in two studies, vitamin D was used for five days; and in one study, vitamin D was used for two days. One study excluded children whose vitamin D levels were normal. One study reported the cause of children's pneumonia.

Study funding sources

One study was funded by the New Zealand Aid Corporation; one was funded by an institutional grant; and five studies were unfunded.

Key results

We are uncertain as to whether vitamin D has an important effect on outcomes due to the very-low quality of the evidence. Vitamin D may slightly decrease the time taken to get better from acute pneumonia (by 60 minutes) and the risk of death, and Vitamin D may increase the length of time in hospital (by 30 minutes) and the time taken for fever to resolve (by 90 minutes). However, there was no significant difference between groups for these outcomes. No major adverse events were reported.

Quality of the evidence

The quality of the evidence was very low, except for time to resolution of acute illness, which we assessed as low quality. We identified problems with the study methods and reporting, resulting in lack of precision in the included studies.

Authors' conclusions: 

We are uncertain as to whether vitamin D has an important effect on outcomes because the results were imprecise. No major adverse events were reported. We assessed the quality of the evidence as very low to low. Several trials are ongoing and may provide additional information.

Read the full abstract...
Background: 

Children with acute pneumonia may be vitamin D deficient. Clinical trials have found that prophylactic vitamin D supplementation decreases the risk of developing pneumonia in children. Data on the therapeutic effects of vitamin D in acute childhood pneumonia are limited.

Objectives: 

To evaluate the efficacy and safety of vitamin D supplementation as an adjunct to antibiotics for the treatment of acute childhood pneumonia.

Search strategy: 

We searched CENTRAL (2017, Issue 7), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; Ovid MEDLINE Epub Ahead of Print; In-Process & Other Non-Indexed Citations; Ovid MEDLINE Daily and Ovid MEDLINE (1946 to July Week 4, 2017); and Embase (2010 to 28 July 2017). We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 28 July 2017. There were no language restrictions.

Selection criteria: 

Randomised controlled trials (RCTs) including children (aged over one month and up to five years) hospitalised with acute community-acquired pneumonia, as defined by the WHO acute respiratory infection guidelines, that compared vitamin D supplementation with control.

Data collection and analysis: 

Two review authors independently assessed studies for inclusion and extracted data. For dichotomous data, we extracted the number of participants experiencing the outcome and the total number of participants in each treatment group. For continuous data, we used the arithmetic mean and standard deviation (SD) for each treatment group together with numbers of participants in each group. We used standard methodological procedures expected by Cochrane.

Main results: 

We included seven RCTs conducted in low-income countries that involved 1529 children (780 with pneumonia and 749 with severe or very severe pneumonia). Four studies used a single 100,000 IU dose of vitamin D₃ at the onset of illness or within 24 hours of hospital admission; two used a daily dose of oral vitamin D₃ (1000 IU for children aged up to one year and 2000 IU for children aged over one year) for five days; and one used a daily dose of oral vitamin D₃ (50,000 IU) for two days. One study reported microbiological and radiological diagnosis of pneumonia.

The effects of vitamin D on outcomes were inconclusive when compared with control: time to resolution of acute illness (hours) (mean difference (MD) -0.95, 95% confidence interval (CI) -6.14 to 4.24; 3 studies; 935 children; low-quality evidence) mortality rate (risk ratio (RR) 0.97, 95% CI 0.06 to 15.28; 1 study; 193 children; very low-quality evidence); duration of hospitalisation (MD 0.49, 95% CI -8.41 to 9.4; 4 studies; 835 children; very low-quality evidence) and time to resolution of fever (MD 1.66, 95% CI -2.44 to 5.76; 4 studies; 584 children; very low-quality evidence).

No major adverse events were reported.

The GRADE assessment found very low-quality evidence (due to serious study limitations, inconsistencies, indirectness, and imprecision) for all outcomes except time to resolution of acute illness.

One study was funded by the New Zealand Aid Corporation; one study was funded by an institutional grant; and five studies were unfunded.

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