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Review
. 2016 Sep 28;9(9):CD007480.
doi: 10.1002/14651858.CD007480.pub3.

Vitamin A supplementation for the prevention of morbidity and mortality in infants one to six months of age

Aamer Imdad  1 , Zunirah Ahmed, Zulfiqar A Bhutta
Affiliations
Review

Vitamin A supplementation for the prevention of morbidity and mortality in infants one to six months of age

Aamer Imdad et al. Cochrane Database Syst Rev. .

Abstract

Background: Vitamin A deficiency is a significant public health problem in low- and middle-income countries. Vitamin A supplementation provided to infants less than six months of age is one of the strategies to improve the nutrition of infants at high risk of vitamin A deficiency and thus potentially reduce their mortality and morbidity.

Objectives: To evaluate the effect of synthetic vitamin A supplementation in infants one to six months of age in low- and middle-income countries, irrespective of maternal antenatal or postnatal vitamin A supplementation status, on mortality, morbidity and adverse effects.

Search methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE via PubMed (1966 to 5 March 2016), Embase (1980 to 5 March 2016) and CINAHL (1982 to 5 March 2016). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria: Randomised or quasi-randomised, individually or cluster randomised trials involving synthetic vitamin A supplementation compared to placebo or no intervention provided to infants one to six months of age were eligible.

Data collection and analysis: Two review authors assessed the studies for eligibility and assessed their risk of bias and collected data on outcomes.

Main results: The review included 12 studies (reported in 22 publications). The included studies assigned 24,846 participants aged one to six months to vitamin A supplementation or control group. There was no effect of vitamin A supplementation for the primary outcome of all-cause mortality based on seven studies that included 21,339 (85%) participants (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.89 to 1.25; I2 = 0%; test for heterogeneity: P = 0.79; quality of evidence: moderate). Also, there was no effect of vitamin A supplementation on mortality or morbidity due to diarrhoea and respiratory tract infection. There was an increased risk of bulging fontanelle within 24 to 72 hours of supplementation in the vitamin A group compared to control (RR 3.10, 95% CI 1.89 to 5.09; I2 = 9%, test for heterogeneity: P = 0.36; quality of evidence: high). There was no reported subsequent increased risk of death, convulsions or irritability in infants who developed bulging fontanelle after vitamin A supplementation, and it resolved in most cases within 72 hours. There was no increased risk of other adverse effects such as vomiting, irritability, diarrhoea, fever and convulsions in the vitamin A supplementation group compared to control. Vitamin A supplementation did not have any statistically significant effect on vitamin A deficiency (RR 0.86, 95% CI 0.70 to 1.06; I2 = 27%; test for heterogeneity: P = 0.25; quality of evidence: moderate).

Authors' conclusions: There is no convincing evidence that vitamin A supplementation for infants one to six months of age results in a reduction in infant mortality or morbidity in low- and middle-income countries. There is an increased risk of bulging fontanelle with vitamin A supplementation in this age group; however, there were no reported subsequent complications because of this adverse effect.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram: review update.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 1 All‐cause mortality: longest follow‐up.
1.2
1.2. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 2 Diarrhoea‐specific mortality at longest follow‐up.
1.3
1.3. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 3 Acute respiratory infection‐specific mortality at longest follow‐up.
1.4
1.4. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 4 Meningitis‐specific mortality.
1.5
1.5. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 5 Morbidity: diarrhoea: point prevalence.
1.6
1.6. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 6 Morbidity: lower respiratory tract infection: period prevalence.
1.7
1.7. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 7 Morbidity: fever: period prevalence.
1.8
1.8. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 8 Adverse effects: bulging fontanelle.
1.9
1.9. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 9 Adverse effects: vomiting.
1.10
1.10. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 10 Adverse effects: irritability.
1.11
1.11. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 11 Adverse effects: diarrhoea.
1.12
1.12. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 12 Adverse effects: fever.
1.13
1.13. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 13 Adverse effects: convulsions.
1.14
1.14. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 14 Vitamin A deficiency: retinol < 0.7 μmol/L.
1.15
1.15. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 15 Subgroup analysis: all‐cause mortality: co‐supplementation with vaccination.
1.16
1.16. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 16 Subgroup analysis: all‐cause mortality: maternal vitamin A supplementation.
1.17
1.17. Analysis
Comparison 1 Young infant vitamin A supplementation versus placebo, Outcome 17 Subgroup analysis: adverse effects: bulging fontanelle: supplementation at the time of vaccination.
See this image and copyright information in PMC

Comment in

References

References to studies included in this review

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Newton 2005 {published data only}
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Newton 2005 (2) {published data only}
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Newton 2010 {published data only}
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References to studies excluded from this review

Ahmad 2014 {published data only}
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Basu 2003 {published data only}
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Benn 2008 {published data only}
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Benn 2010 {published data only (unpublished sought but not used)}
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Biering‐Sørensen 2013 {published data only}
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Coles 2001 {published data only}
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Coles 2011 {published data only}
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Coutsoudis 1999 {published data only}
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Darboe 2007 {published data only}
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Delvin 2000 {published data only}
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Fernandes 2012 {published data only}
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Fisker 2011 {published data only}
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Garcia 2011 {published data only}
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Humphrey 1996 {published data only}
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Humphrey 2006 {published data only}
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Katz 2000 {published data only}
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Kiraly 2013 {published data only}
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Kirkwood 2010 {published data only}
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Klemm 2008 {published data only}
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Kumwenda 2002 {published data only}
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Lund 2014 {published data only}
    1. Lund N, Biering‐Sorensen S, Andersen A, Monteiro I, Camala L, Jorgensen MJ, et al. Neonatal vitamin A supplementation associated with a cluster of deaths and poor early growth in a randomised trial among low‐birth‐weight boys of vitamin A versus oral polio vaccine at birth. BMC Pediatrics 2014;14:214. [PUBMED: 25163399] - PMC - PubMed
Malaba 2005 {published data only}
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McDonald 2014 {published data only}
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Miller 2006 {published data only}
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Nankabirwa 2011 {published data only}
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Rice 1999 {published data only}
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Roy 1997 {published data only}
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Schmidt 2002 {published data only}
    1. Schmidt MK, Muslimatun S, Schultink W, West CE, Hautvast JG. Randomised double‐blind trial of the effect of vitamin A supplementation of Indonesian pregnant women on morbidity and growth of their infants during the first year of life. European Journal of Clinical Nutrition 2002;56(4):338‐46. [PUBMED: 11965510] - PubMed
Stabell 1995 {published data only}
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Stoltzfus 1993 {published data only}
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Venkatarao 1996 {published data only}
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Vinutha 2000 {published data only}
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