Annex 1GRADE “Summary of findings” table
Vitamin A supplementation in infants and young children 6–59 months of age
Patient or population: Infants and young children 6–59 months of age
Settings: Low- and middle-income countries
Intervention: Vitamin A supplementation
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| Outcomes | Relative effect
(95% CI) | Number of participants
(studies) | Quality of the evidence
(GRADE)* | Comments |
|---|
All-cause mortality
Follow-up: 12–96 weeks | RR 0.76
(0.69–0.83) | 194 798
(17 studies) | ⊕⊕⊕⊕
high | Inclusion of the DEVTA trial reduced the effect size. RR 0.76 (95% CI 0.69–0.83) to RR 0.88 (95% CI 0.84–0.94) |
All-cause mortality (HIV+ children)
Hospital files or verbal autopsy forms Follow-up: 6–24 months | RR 0.55
(0.37–0.82) | 262
(3 studies) | ⊕⊕⊕⊖
moderate1 | |
Diarrhoea-related mortality
Follow-up: 48–104 weeks | RR 0.72
(0.57–0.91) | 90 951
(7 studies) | ⊕⊕⊕⊖
moderate2 | Total number of participants reflects number randomized to studies. The analysis combined cumulative risk and risk per/1000 years follow-up |
Measles-related mortality
Follow-up: 52–104 weeks | RR 0.80
(0.51–1.24) | 88 261
(5 studies) | ⊕⊕⊕⊖
moderate3 | Total number of participants reflects number randomized to studies. The analysis combined cumulative risk and risk per/1000 years follow-up |
Lower respiratory tract infection-related mortality
Follow-up: 48–104 weeks | RR 0.78
(0.54–1.14) | 90 951
(7 studies) | ⊕⊕⊖⊖
low2,3 | Total number of participants reflects number randomized to studies. The analysis combined cumulative risk and risk per/1000 years follow-up |
Diarrhoea-related hospital admission (HIV+ children)
Maternal recall
Follow-up: 6–18 months | RR 0.25
(0.05–1.15) | 194
(1 study) | ⊕⊕⊕⊖
moderate4 | Only one study reported on this outcome |
Diarrhoea incidence
Ratio of rates of episodes per child
Follow-up: 24–60 weeks | RR 0.85
(95% CI 0.82–0.87) | 69 972
(13 studies) | ⊕⊕⊖⊖
low5,6 | |
Acute respiratory infection-related hospital admission (HIV+ children)
Maternal recall
Follow-up: 6–18 months | RR 0.6
(0.15–2.44) | 194
(1 study) | ⊕⊕⊕⊖
moderate4 | Only one study reported on this outcome |
Lower respiratory tract infection-related morbidity – incidence
Mean episodes/child per year
Follow–up: mean 52 weeks | RR 1.14
(95% CI 0.95–1.37) | 19 566
(9 studies) | ⊕⊖⊖⊖
very low7-9 | |
Vomiting
Follow-up: 0.14–52 weeks | RR 2.75
(1.81–4.19) | 2994
(3 studies) | ⊕⊕⊖⊖
low10,11 | |
CI, confidence interval; RR, risk ratio; HIV, human immunodeficiency virus.
- *
GRADE Working Group grades of evidence:
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We have moderate confidence in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of the effect.
- 1
Imprecision due to few deaths and small HIV+ groups in the three studies included in the meta-analysis.
- 2
The risk of bias assessments determined that Daulaire (1992) and Herrera (1992) were at risk of selection bias. Detection bias put the results of Daulaire (1992) at a high risk of bias. Attrition bias was considered to put the results of Chowdhury (2002) at a high risk of bias. Baseline imbalance was noted for Agarwal (1995).
- 3
The wide confidence intervals around the pooled effect estimate included both a reduction and an increase in the risk of mortality with vitamin A.
- 4
Imprecision due to wide variation in confidence intervals, which translates into wide variation in absolute effect.
- 5
The risk of bias assessment determined that four studies contributing just over 25% weight of the estimated effect were at risk of selection or attrition bias.
- 6
The I2 was 95%, and the results of Cheng (1993), Chowdhury (2002) and Herrera (2002) demonstrated clear evidence of benefit and were discordant with the results of the other studies.
- 7
The risk of bias assessment determined that Cheng (1993), Chowdhury (2002) and Kartasasmita (1995) were at high risk of attrition bias.
- 8
Diagnostic procedures were not consistent across the studies.
- 9
The confidence intervals around the pooled effect included small benefit and a meaningful increase in the risk of respiratory tract infections.
- 10
The follow-up was spread between 1 day and 52 weeks.
- 11
There was some evidence of underreporting of adverse events in some of the studies, and the low number of trials giving data in relation to the large number of studies included overall, means that this selective reporting of adverse events cannot be excluded.
For details of studies included in the review, see reference (4).
