Intervention Review

You have free access to this content

Vitamin A for treating measles in children

  1. Hui Ming Yang*,
  2. Meng Mao,
  3. Chaomin Wan

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 8 JUL 2009

Assessed as up-to-date: 28 FEB 2011

DOI: 10.1002/14651858.CD001479.pub3

Database Title

Additional Information

How to Cite

Yang HM, Mao M, Wan C. Vitamin A for treating measles in children. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD001479. DOI: 10.1002/14651858.CD001479.pub3.

Author Information

  1. West China Second University Hospital, West China Women's and Children's Hospital, Department of Pediatrics, Chengdu, Sichuan, China

*Hui Ming Yang, Department of Pediatrics, West China Second University Hospital, West China Women's and Children's Hospital, No. 17, Section Three, Ren Min Nan Lu Avenue, Chengdu, Sichuan, 610041, China. yanghuiming03@163.com. yang_huiming@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 8 JUL 2009

SEARCH

ARTICLE TOOLS

View Full Article (HTML) Summary (58K)Standard (394K)Full (481K)
 
Characteristics of included studies [ordered by study ID]
Barclay 1987
MethodsRandomized clinical trial using a random number table
Participants180 children with measles in hospital
Interventions200,000 IU vitamin A orally for 2 days, or routine treatment without vitamin A
OutcomesDeath
NotesQuality score 3
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized clinical trial using a random numbers table
Allocation concealment (selection bias)Low riskAdequate
Blinding (performance bias and detection bias)
All outcomes		Low riskThe staff and participants were blinded




Coutsoudis 1991
MethodsRandomized, placebo-controlled, double-blind trial
Participants60 children aged 4 to 24 months hospitalized with complicated measles
InterventionsWHO recommended dose (54.5 mg < 12 months or 109 mg > 12 months) of retinyl palmitate drops or a placebo syrup
OutcomesDeath
Recovery in < 8 days
Duration of pneumonia in days
Duration of diarrhea in days
Duration of fever in days
Herpes stomatitis, laryngeo-tracheobronchitis, integrated morbidity score
NotesQuality score 5
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskThe patients were allocated to treatment or placebo groups according to a random numbers table
The treatment and placebo-dropper bottles were number-coded
Allocation concealment (selection bias)Low riskAdequate
Blinding (performance bias and detection bias)
All outcomes		Low riskDouble-blinded
Other biasUnclear riskVitamin A or placebo was administered by the same person
Blinding of participants and personnel (performance bias)
All outcomes		Low risk
Blinding of outcome assessment (detection bias)
All outcomes		Low risk




Dollimore 1997
MethodsRandomized, placebo-controlled, double-blind trial
Participants946 children aged 6 to 90 months, in the community
Interventions100,000 IU of vitamin A for children aged 6 to 11 months or 200,000 IU of vitamin A for older children every 4 months for 2 years
OutcomesDeath
NotesQuality score 5
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskThe study area was divided into 185 small geographic units, each comprising 30 to 77 compounds. The units were randomized to receive either vitamin A or placebo using a method of randomization of clusters
Allocation concealment (selection bias)Low riskAdequate
Blinding (performance bias and detection bias)
All outcomes		Low riskDouble-blinded
Blinding of participants and personnel (performance bias)
All outcomes		Low risk
Blinding of outcome assessment (detection bias)
All outcomes		Low risk




Ellison 1932
MethodsControlled trial
Participants600 children in 2 hospital wards
Interventions300 Carr and Price units for 7 to 12 days
OutcomesDeath
NotesQuality score 1
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskNo randomization
Allocation concealment (selection bias)High riskInadequate
Blinding (performance bias and detection bias)
All outcomes		Low risk




Hussey 1990
MethodsRandomized, double-blind trial
Participants189 children < 13 years of age, hospitalized with measles complicated with pneumonia, diarrhea or croup
InterventionsEither 200,000 IU retinyl palmitate given orally for 2 days or a placebo, within 5 days of the onset of the rash
Outcomes> 10 days with pneumonia
> 10 days of diarrhea
Croup, duration of diarrhea and pneumonia, herpes stomatitis
Transferred to intensive care
Hospital stay in days
Death
NotesQuality score 4
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized clinical trial using a random numbers table
Allocation concealment (selection bias)Low riskAdequate
Blinding (performance bias and detection bias)
All outcomes		Low riskDouble-blinded
Blinding of participants and personnel (performance bias)
All outcomes		Low risk




Kawasaki 1999
MethodsRandomized controlled trial
Participants105 children with measles age 5 months to 4 years in hospital
InterventionsOral vitamin A (100,000 IU) supplementation
OutcomesPneumonia, laryngitis, duration of cough, fever and hospitalization
NotesQuality score 3
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomized clinical trial using a random numbers table
Allocation concealment (selection bias)Low riskAdequate
Selective reporting (reporting bias)Low risk
Blinding of participants and personnel (performance bias)
All outcomes		Low risk




Ogaro 1993
MethodsRandomized, double-blind trial
Participants294 children under 5 years admitted to hospital with measles in Kenya
Interventions50,000 IU of vitamin A (retinyl palmitate) to children < 6 months, 100,000 IU to children between 6 to 12 months, and 200,000 IU to children > 12 months in a single dose on admission
OutcomesCroup, pneumonia, diarrhea, otitis media, death
NotesQuality score 3
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized clinical trial using a random numbers table
Allocation concealment (selection bias)Low riskAdequate
Blinding (performance bias and detection bias)
All outcomes		Low riskDouble-blinded




Rosales 1996
MethodsRandomized, double-blind, placebo-controlled clinical trial
Participants200 children with acute measles not requiring hospitalization
InterventionsSingle dose of 200,000 IU vitamin A in oil (100,000 IU for infants) or placebo
OutcomesMeasles-associated cough or pneumonia, croup, fever, diarrhea
Failure to improve from pneumonia
NotesQuality score 5
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk1:1 randomization scheme was used to allocate vitamin A or placebo treatment

Allocation of bottle codes for each series of 100 participants identification numbers was accomplished using a random numbers table
Allocation concealment (selection bias)Low riskAdequate
Blinding (performance bias and detection bias)
All outcomes		Low riskDouble-blinded
Other biasLow risk
Blinding of participants and personnel (performance bias)
All outcomes		Low risk
Blinding of outcome assessment (detection bias)
All outcomes		Low risk
 mo = months


 
Characteristics of excluded studies [ordered by study ID]
StudyReason for exclusion
Chowdhury 2002The trial studied the effect of vitamin A supplementation on childhood morbidity but not for treating measles in children


 
Comparison 1. Vitamin A versus placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Mortality8Risk Ratio (M-H, Random, 95% CI)Subtotals only
    1.1 All patients (seven studies)
71974Risk Ratio (M-H, Random, 95% CI)0.83 [0.51, 1.34]
    1.2 200,000 IU or more
3429Risk Ratio (M-H, Random, 95% CI)0.40 [0.19, 0.87]
    1.3 Less than 200,000 IU
31094Risk Ratio (M-H, Random, 95% CI)0.77 [0.34, 1.78]
    1.4 Age two years or less (> 200,000 IU)
3309Risk Ratio (M-H, Random, 95% CI)0.21 [0.07, 0.66]
    1.5 Age more than two years (> 200,000 IU)
2120Risk Ratio (M-H, Random, 95% CI)0.98 [0.33, 2.94]
    1.6 Oil-based vitamin A
3674Risk Ratio (M-H, Random, 95% CI)0.85 [0.44, 1.61]
    1.7 Water-based vitamin A
2249Risk Ratio (M-H, Random, 95% CI)0.23 [0.06, 0.89]
    1.8 Areas with case-fatality 6% or less
2494Risk Ratio (M-H, Random, 95% CI)1.24 [0.53, 2.89]
    1.9 Areas with case-fatality > 10%
3429Risk Ratio (M-H, Random, 95% CI)0.40 [0.19, 0.87]
    1.10 Pneumonia-specific mortality
4723Risk Ratio (M-H, Random, 95% CI)0.57 [0.24, 1.37]
    1.11 All patients (eight studies)
82574Risk Ratio (M-H, Random, 95% CI)0.70 [0.42, 1.15]
 2 Morbidity (dichotomous data)5Risk Ratio (M-H, Random, 95% CI)Totals not selected
    2.1 Post-measles croup
4Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
    2.2 Development of pneumonia
2Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
    2.3 Development of diarrhea
2Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
    2.4 Herpes stomatitis
2Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
 3 Morbidity (continuous data)3Mean Difference (IV, Random, 95% CI)Subtotals only
    3.1 Duration of pneumonia
2249Mean Difference (IV, Random, 95% CI)-3.69 [-7.53, 0.16]
    3.2 Duration of diarrhea in days
2249Mean Difference (IV, Random, 95% CI)-1.92 [-3.40, -0.44]
    3.3 Duration of fever in days
2149Mean Difference (IV, Random, 95% CI)-1.01 [-1.89, -0.13]
    3.4 Hospital stay in days
2278Mean Difference (IV, Random, 95% CI)-2.39 [-6.60, 1.83]
    3.5 Days of cough
189Mean Difference (IV, Random, 95% CI)0.00 [-2.71, -1.29]
    3.6 Integrated morbidity score
160Mean Difference (IV, Random, 95% CI)-1.13 [-1.28, -0.98]
 4 Morbidity (single-study outcomes)5Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    4.1 Development of otitis media
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.2 Recovery from diarrhea in < five days
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.3 Development of acute laryngitis
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.4 Cough in week two
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.5 Compete clinical recovery in < eight days
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.6 Asymptomatic in week two
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.7 Transferred to intensive care
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.8 Diarrhea for more than 10 days
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.9 Diarrhea for 14 days
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.10 Pneumonia for more than 10 days
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.11 Pneumonia for 14 days
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
    4.12 Recovery from pneumonia in < eight days
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
 
Summary of findings for the main comparison.
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
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)		No of participants
(studies)		Quality of the evidence
(GRADE)		Comments
Assumed riskCorresponding risk
Placebo or no vitamin AVitamin A
MortalityLow-risk population3RR 0.70 (0.42 to 1.15)2574
(8)		+++O
moderate		Areas with case-fatality > 10%

Age two years or less
98 per 100069 per 1000
(41 to 113)
High-risk population
107 per 100075 per 1000
(45 to 123)
Pneumonia-specific mortality50 per 100028 per 1000
(12 to 68)		RR 0.57 (0.24 to 1.37)723
(4)		+++O
moderate
Duration of pneumoniaThe 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 daysThe 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 daysThe 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 daysThe 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.
View Full Article (HTML) Summary (58K)Standard (394K)Full (481K)