Vitamin A for treating measles in children

Hui Ming Yang; Meng Mao; Chaomin Wan

doi:10.1002/14651858.CD001479.pub3

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Figure 1

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 Vitamin A versus placebo, Outcome 1 Mortality.

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Analysis 1.2

Comparison 1 Vitamin A versus placebo, Outcome 2 Morbidity (dichotomous data).

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Analysis 1.3

Comparison 1 Vitamin A versus placebo, Outcome 3 Morbidity (continuous data).

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Analysis 1.4

Comparison 1 Vitamin A versus placebo, Outcome 4 Morbidity (single‐study outcomes).

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Vitamin A compared with placebo or no vitamin A for treating measles in children
Patient or population: children with measles Settings: in hospital or in the community¹ Intervention: vitamin A² Comparison: placebo or no vitamin A
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo or no vitamin A	Vitamin A
Mortality	Low‐risk population³		RR 0.70 (0.42 to 1.15)	2574 (8)	+++O moderate	Areas with case‐fatality > 10% Age two years or less
	98 per 1000	69 per 1000 (41 to 113)
	High‐risk population
	107 per 1000	75 per 1000 (45 to 123)
Pneumonia‐specific mortality	50 per 1000	28 per 1000 (12 to 68)	RR 0.57 (0.24 to 1.37)	723 (4)	+++O moderate
Duration of pneumonia	The mean duration of pneumonia ranged across control groups from of pneumonia from 5.7 to 12.37 days	The mean duration of pneumonia in the intervention groups was 3.69 days shorter (95% CI ‐7.53 to 0.16)		249 (2)	+++O moderate
Duration of diarrhea in days	The mean duration of diarrhea in days ranged across control groups from 4.5 to 8.45 days	The mean duration of diarrhea in days in the intervention groups was 1.92 lower (95% CI ‐3.40 to ‐0.44)		249 (2)	+++O moderate
Hospital stay in days	The mean days stay in hospital ranged across control groups from 5.9 to 15.24	The mean stay in hospital in the intervention groups was 2.39 days less (95% CI ‐6.60 to 1.83 )		278 (2)	+++O moderate
Duration of fever in days	The mean duration of fever ranged across control groups from 4.2 to 8.3 days	The mean duration of fever in the intervention groups was 1.01 days less (95% CI ‐1.89 to ‐0.13)		149 (2)	+++O moderate
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
^1. The evidence from these studies can only be generalized in relation to low‐income countries. There is limited information to permit a generalization in relation to high‐income countries. The only study carried out in a developed country (Japan) used one‐fourth of the recommended dose (100,000 IU), showed a reduced morbidity and did not report any toxicity. ^2. All the Vitamin A supplements in the eight trials included in this review were administrated orally. Two studies used water‐based vitamin A formulations while the other three used an oil‐based formulation. Different doses of vitamin A were used in this review. ^3. Three trials recruited high‐risk participants defined as those living in areas with case‐fatality > 10% or aged two years or less. The incidence for five trials that excluded high‐risk participants was 9.8% and the incidence for the two trials that recruited high‐risk participants (with at least one risk factor) was 10.7%. We have rounded these off to 98 and 107 per 1000 respectively.

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Comparison 1. Vitamin A versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	8		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 All patients (seven studies)	7	1974	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.51, 1.34]
1.2 200,000 IU or more	3	429	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.19, 0.87]
1.3 Less than 200,000 IU	3	1094	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.34, 1.78]
1.4 Age two years or less (> 200,000 IU)	3	309	Risk Ratio (M‐H, Random, 95% CI)	0.21 [0.07, 0.66]
1.5 Age more than two years (> 200,000 IU)	2	120	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.33, 2.94]
1.6 Oil‐based vitamin A	3	674	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.44, 1.61]
1.7 Water‐based vitamin A	2	249	Risk Ratio (M‐H, Random, 95% CI)	0.23 [0.06, 0.89]
1.8 Areas with case‐fatality 6% or less	2	494	Risk Ratio (M‐H, Random, 95% CI)	1.24 [0.53, 2.89]
1.9 Areas with case‐fatality > 10%	3	429	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.19, 0.87]
1.10 Pneumonia‐specific mortality	4	723	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.24, 1.37]
1.11 All patients (eight studies)	8	2574	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.42, 1.15]
2 Morbidity (dichotomous data) Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

2.1 Post‐measles croup	4		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 Development of pneumonia	2		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.3 Development of diarrhea	2		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.4 Herpes stomatitis	2		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Morbidity (continuous data) Show forest plot	3		Mean Difference (IV, Random, 95% CI)	Subtotals only

3.1 Duration of pneumonia	2	249	Mean Difference (IV, Random, 95% CI)	‐3.69 [‐7.53, 0.16]
3.2 Duration of diarrhea in days	2	249	Mean Difference (IV, Random, 95% CI)	‐1.92 [‐3.40, ‐0.44]
3.3 Duration of fever in days	2	149	Mean Difference (IV, Random, 95% CI)	‐1.01 [‐1.89, ‐0.13]
3.4 Hospital stay in days	2	278	Mean Difference (IV, Random, 95% CI)	‐2.39 [‐6.60, 1.83]
3.5 Days of cough	1	89	Mean Difference (IV, Random, 95% CI)	0.00 [‐2.71, ‐1.29]
3.6 Integrated morbidity score	1	60	Mean Difference (IV, Random, 95% CI)	‐1.13 [‐1.28, ‐0.98]
4 Morbidity (single‐study outcomes) Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.1 Development of otitis media	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Recovery from diarrhea in < five days	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 Development of acute laryngitis	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.4 Cough in week two	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.5 Compete clinical recovery in < eight days	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.6 Asymptomatic in week two	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.7 Transferred to intensive care	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.8 Diarrhea for more than 10 days	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.9 Diarrhea for 14 days	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.10 Pneumonia for more than 10 days	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.11 Pneumonia for 14 days	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.12 Recovery from pneumonia in < eight days	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. Vitamin A versus placebo

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