Routine vitamin A supplementation for the prevention of blindness due to measles infection in children

 

Characteristics of included studies [ordered by study ID]

Coutsoudis 1991

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Methods	Randomised, double-blind, placebo-controlled trial Allocation sequence was generated using a table of random numbers Unit of randomisation was individual participants Treatment and placebo dropper (dispenser bottle) were number-coded Study duration was 7 months
Participants	Inclusion criteria: measles severe enough to warrant hospital admission, measles cases with pneumonia and diarrhoea, age between 4 and 24 months Exclusion criteria: mild cases of measles (without pneumonia and diarrhoea), children > 24 months, rash > 5 days, vitamin A administration before admission, children with laryngotracheobronchitis
Interventions	Vitamin A versus placebo syrup Investigators used the WHO-recommended dose for vitamin A (54.5 mg for children < 12 months, 109 mg for children ≥ 12 months) Vitamin A given on days 2, 8 and 42 Follow up was 6 months
Outcomes	Extent of pneumonia, duration of fever, diarrhoea and pneumonia, incidence of herpes stomatitis and laryngotracheobronchitis. Serum zinc, serum vitamin E, serum retinol, serum retinol-binding protein (RBP), serum albumin and pre-albumin, weight gain Outcomes were measured on days 8, 42 and 6 months post-intervention
Notes	Study was carried out in 1989 Normal-phase, high-pressure liquid chromatography (HPLC) using fluorescent detection was used to estimate serum retinol level.
Risk of bias
Item	Authors' judgement	Description
Adequate sequence generation?	Yes	Adequate: allocation sequence was generated by table of random numbers
Allocation concealment?	Yes	Adequate: treatment and placebo dropper (dispenser bottle) was number-coded
Blinding? All outcomes	Yes	Adequate: double-blind
Incomplete outcome data addressed? All outcomes	Yes	All study participants were accounted for
Free of selective reporting?	Yes	All pre-stated outcomes were reported
Free of other bias?	No	Not all randomised participants were included in the analysis

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Rosale 1996

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Methods	Randomised controlled, double-blind trial Allocation sequence generated by table of random numbers Unit of randomisation: individual participants Study duration was 7 months
Participants	Inclusion criteria: prodromal or effervescent measles, consent by parents, confirmation by a 4-fold increase in measles antibody titre at end of week 2 Exclusion: cases requiring hospitalisation, xerophthalmia, severe under-nutrition, refusal to give consent by parents
Interventions	Vitamin A in oil given as a single dose of 210 microgram (200,000 IU) with vitamin E (42.4 microgram) versus placebo Co-interventions: eye ointment, paracetamol, aspirin, tetracycline, intramuscular penicillin, oral rehydration fluids, gentian violet, cough mixture Follow up was for 4 weeks
Outcomes	Cough, pneumonia, serum retinol level, nutritional status Outcomes were measured 2 weeks and 42 days post-intervention
Notes	Both nutritional status and eye examination were reported done at follow-up visits but no results for these were presented Serum retinol levels were determined by high-pressure, liquid chromatography
Risk of bias
Item	Authors' judgement	Description
Adequate sequence generation?	Yes	Adequate: sequence was generated using a table of random numbers
Allocation concealment?	Yes	Adequate: codes were used on bottles
Blinding? All outcomes	Yes	Adequate: double-masking of the dispenser bottles which were also number-coded
Incomplete outcome data addressed? All outcomes	Yes	All participants were accounted for
Free of selective reporting?	No	Eye examination done not reported
Free of other bias?	No	Not all randomised participants were included in the study

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Characteristics of excluded studies [ordered by study ID]

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Study	Reason for exclusion
Dollimore 1997	Intervention not targeted at measles participants. No outcome of interest to the review question was measured
Hussey 1990	No outcome of interest to the review question

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Comparison 1. Vitamin A versus placebo

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Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Serum retinol 2 weeks post-intervention	1	155	Mean Difference (IV, Fixed, 95% CI)	2.67 [-0.29, 5.63]
2 Serum retinol 1 week post-intervention	1	17	Mean Difference (IV, Fixed, 95% CI)	9.45 [2.19, 16.71]
3 Serum retinol 6 weeks post-intervention	1	39	Mean Difference (IV, Fixed, 95% CI)	2.56 [-5.28, 10.40]
4 Serum retinol mean change day 8 (1 week post-intervention)	1	17	Mean Difference (IV, Fixed, 95% CI)	8.62 [1.22, 16.02]
5 Weight gain 6 weeks post-intervention	1	48	Mean Difference (IV, Fixed, 95% CI)	0.39 [-0.04, 0.82]
6 Weight gain 6 months post-intervention	1	36	Mean Difference (IV, Fixed, 95% CI)	0.52 [-0.08, 1.12]

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Summary of findings for the main comparison.

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Vitamin A compared with placebo or no vitamin A for prevention of blindness
Patient or population: children with measles infection and no clinically demonstrable vitamin A deficiency Settings: resource-limited countries Intervention: vitamin A 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	Vitamin A
Blindness	See comment		Not estimable	260 (2 studies)	See comment	None of the studies reported blindness as an end point
Serum retinol (1 week post-intervention) (mean X [µg/dL] ± standard error SE)	X ± SE in the placebo group was 29.0 ± 2.2 (95% CI 24.8 to 33.3)	X ± SE in the intervention group was 38.5 ±3.0 (95% CI 32.6 to 44.4)	9.5 higher (2.2 higher to 16.7 higher)	17 (1 study)	+++O moderate
Serum retinol (2 weeks post-intervention) (mean X [µg/dL] ± standard error SE)	X ± SE in the placebo group was 19.0 ± 0.7 (95% CI 17.6 to 20.3)	X ± SE in the intervention group was 21.6 ± 1.1 (95% CI 19.5 to 23.7)	2.7 higher (0.3 lower to 5.6 higher)	155 (1 study)	+++O moderate
Serum retinol (6 weeks post-intervention) (mean X [µg/dL] ± standard error SE)	X ± SE in the placebo group was 28.5 ± 2.4 (95% CI 23.86 to 33.12)	X ± SE in the intervention group was 31.1 ± 3.2 (95% CI 24.7 to 37.4)	2.6 higher (5.3 lower to 10.4 higher)	39 (1 study)	+++O moderate
Serum retinol (mean change 1 week post-intervention (mean X [µg/dL] ± standard error SE)	X ± SE in the placebo group was 17.3 ± 1.9 (95% CI 13.7 to 21.0)	X ± SE in the placebo group was 26.0 ± 3.3 (95% CI 19.6 to 32.4)	8.6 higher (1.2 higher to 16.0 higher)	17 (1 study)	+++O moderate
Weight gain 6 weeks post-intervention (mean X [kg] ± standard error SE)	X ± SE in the placebo group was 0.9 ± 0.1 (95% CI 0.6 to 1.2)	X ± SE in the intervention group was 1.3 ± 0.2 (95% CI 1.3 to 1.3)	0.4 higher (0.04 lower to 0.8 higher)	48 (1 study)	+++O moderate
Weight gain 6 months post-intervention (mean X [kg] ± standard error SE)	X ± SE in the placebo group was 2.4 ± 0.2 (95% CI 2.0 to 2.8)	X ± SE in the intervention group was 2.9 ± 0.2 (95% CI 2.4 to 3.3)	0.5 higher (0.1 lower to 1.1 higher)	36 (1 study)	+++O moderate
Other ocular morbidities (night blindness, conjunctival xerosis, Bitot's spot, corneal xerosis, xerophthalmia, corneal ulceration, corneal scars)	See comment		Not estimable	260 (2 studies)	See comment	None of the studies reported ocular morbidities as end points.
Adverse events	See comment		Not estimable	260 (2 studies)	See comment	0 participants had adverse events
*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% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; SE: standard error; GRADE: GRADE Working Group grades of evidence (see explanations)

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 Assumed risk and corresponding risk in the table are from a single study in each case, and are not the usual combined mean or median risks across multiple studies.
GRADE Working Group grades of evidence
High quality (++++): Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality (+++O): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality (++OO): 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 (+OOO): We are very uncertain about the estimate.