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Meta-Analysis
. 2017 Mar 11;3(3):CD008524.
doi: 10.1002/14651858.CD008524.pub3.

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age

Aamer Imdad  1 , Evan Mayo-Wilson  2 , Kurt Herzer  3 , Zulfiqar A Bhutta  4
Affiliations
Meta-Analysis

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age

Aamer Imdad et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation for children aged 6 to 59 months. There are new data available from recently published randomised trials since the previous publication of this review in 2010, and this update incorporates this information and reviews the evidence.

Objectives: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years.

Search methods: In March 2016 we searched CENTRAL, Ovid MEDLINE, Embase, six other databases, and two trials registers. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies.

Selection criteria: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation.

Data collection and analysis: For this update, two reviewers independently assessed studies for inclusion and abstracted data, resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence.

Main results: We identified 47 studies (4 of which are new to this review), involving approximately 1,223,856 children. Studies took place in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most of the studies included equal numbers of girls and boys and lasted about a year. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for vitamin A compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-quality evidence). This result was sensitive to choice of model, and a random-effects meta-analysis showed a different summary estimate (24% reduction: RR 0.76, 95% CI 0.66 to 0.88); however, the confidence intervals overlapped with that of the fixed-effect model. Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 participants; high-quality evidence). There was no significant effect for VAS on mortality due to measles, respiratory disease, and meningitis. VAS reduced incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies; 77,946 participants; low-quality evidence) and measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies; 19,566 participants; moderate-quality evidence). However, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies; 10,541 participants; moderate-quality evidence).

Authors' conclusions: Vitamin A supplementation is associated with a clinically meaningful reduction in morbidity and mortality in children. Therefore, we suggest maintaining the policy of universal supplementation for children under five years of age in populations at risk of VAD. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented vitamin A deficiency, it would be unethical to conduct placebo-controlled trials.

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Conflict of interest statement

The World Health Organization (WHO) funded this review. The authors alone are responsible for the opinions and views expressed in this publication.

Aamer Imdad was paid for writing this review by the WHO. Evan Mayo‐Wilson ‐ none known. Zulfiqar A Bhutta's (ZB) institution received a grant from the WHO for this review and two additional vitamin A related Cochrane reviews (Imdad 2016; Haider 2017). ZB is an Editor for Cochrane Developmental, Pyschosocial and Learning Problems.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Vitamin A versus Control, outcome: 1.1 All‐cause mortality at longest follow‐up.
4
4
Forest plot of comparison: 1 Vitamin A versus Control, outcome: 1.8 Diarrhoea incidence at longest follow‐up.
5
5
Funnel plot of comparison: 1 Vitamin A versus Control, outcome: 1.1 All‐cause mortality at longest follow‐up.
6
6
Forest plot of comparison: 1 Vitamin A versus Control, outcome: 1.12 Measles Incidence at Longest Follow‐up.
1.1
1.1. Analysis
Comparison 1 Vitamin A versus Control, Outcome 1 All‐cause mortality at longest follow‐up.
1.2
1.2. Analysis
Comparison 1 Vitamin A versus Control, Outcome 2 All‐cause mortality at longest follow‐up (subgroup analysis): age.
1.3
1.3. Analysis
Comparison 1 Vitamin A versus Control, Outcome 3 All‐cause mortality at longest follow‐up (subgroup analysis): sex.
1.4
1.4. Analysis
Comparison 1 Vitamin A versus Control, Outcome 4 Mortality due to diarrhoea at longest follow‐up.
1.5
1.5. Analysis
Comparison 1 Vitamin A versus Control, Outcome 5 Mortality due to measles at longest follow‐up.
1.6
1.6. Analysis
Comparison 1 Vitamin A versus Control, Outcome 6 Mortality due to meningitis at longest follow‐up.
1.7
1.7. Analysis
Comparison 1 Vitamin A versus Control, Outcome 7 Mortality due to lower respiratory tract infection (LRTI) at longest follow‐up.
1.8
1.8. Analysis
Comparison 1 Vitamin A versus Control, Outcome 8 Diarrhoea incidence at longest follow‐up.
1.9
1.9. Analysis
Comparison 1 Vitamin A versus Control, Outcome 9 Diarrhoea prevalence at longest follow‐up.
1.10
1.10. Analysis
Comparison 1 Vitamin A versus Control, Outcome 10 Measles incidence at longest follow‐up.
1.11
1.11. Analysis
Comparison 1 Vitamin A versus Control, Outcome 11 Malaria incidence at longest follow‐up.
1.12
1.12. Analysis
Comparison 1 Vitamin A versus Control, Outcome 12 Malaria prevalence at longest follow‐up.
1.13
1.13. Analysis
Comparison 1 Vitamin A versus Control, Outcome 13 LRTI incidence at longest follow‐up.
1.14
1.14. Analysis
Comparison 1 Vitamin A versus Control, Outcome 14 LRTI prevalence at longest follow‐up.
1.15
1.15. Analysis
Comparison 1 Vitamin A versus Control, Outcome 15 Bitot's spots prevalence at longest follow‐up.
1.16
1.16. Analysis
Comparison 1 Vitamin A versus Control, Outcome 16 Night blindness incidence at longest follow‐up.
1.17
1.17. Analysis
Comparison 1 Vitamin A versus Control, Outcome 17 Night blindness prevalence at longest follow‐up.
1.18
1.18. Analysis
Comparison 1 Vitamin A versus Control, Outcome 18 Xerophthalmia incidence at longest follow‐up.
1.19
1.19. Analysis
Comparison 1 Vitamin A versus Control, Outcome 19 Xerophthalmia prevalence at longest follow‐up.
1.20
1.20. Analysis
Comparison 1 Vitamin A versus Control, Outcome 20 Hospitalisation: number of children hospitalised once or more at longest follow‐up.
1.21
1.21. Analysis
Comparison 1 Vitamin A versus Control, Outcome 21 Hospitalisation due to diarrhoea at longest follow‐up.
1.22
1.22. Analysis
Comparison 1 Vitamin A versus Control, Outcome 22 Hospitalisation due to LRTI at longest follow‐up.
1.23
1.23. Analysis
Comparison 1 Vitamin A versus Control, Outcome 23 Side effect: vomiting.
1.24
1.24. Analysis
Comparison 1 Vitamin A versus Control, Outcome 24 Side effect: bulging fontanelle.
1.25
1.25. Analysis
Comparison 1 Vitamin A versus Control, Outcome 25 Vitamin A deficiency status: number deficient at longest follow‐up.
1.26
1.26. Analysis
Comparison 1 Vitamin A versus Control, Outcome 26 Vitamin A deficiency status: vitamin A serum retinol level at longest follow‐up.
See this image and copyright information in PMC

Update of

References

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Ross 1993 HEALTH {published data only}
    1. Benn CS, Aaby P, Nielsen J, Binka FN, Ross DA. Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial. American Journal of Clinical Nutrition 2009;90(3):629‐39. [PUBMED: 19640958] - PubMed
    1. Binka FN, Ross DA, Morris SS, Kirkwood BR, Arthur P, Dollimore N, et al. Vitamin A supplementation and childhood malaria in northern Ghana. American Journal of Clinical Nutrition 1995;61(4):853‐9. [PUBMED: 7702031] - PubMed
    1. Dollimore N, Cutts F, Binka FN, Ross DA, Morris SS, Smith PG. Measles incidence, case fatality, and delayed mortality in children with or without vitamin A supplementation in rural Ghana. American Journal of Epidemiology 1997;146(8):646‐54. [PUBMED: 9345118] - PubMed
    1. Filteau SM, Morris SS, Raynes JG, Arthur P, Ross DA, Kirkwood BR, et al. Vitamin A supplementation, morbidity, and serum acute‐phase proteins in young Ghanaian children. American Journal of Clinical Nutrition 1995;62(2):434‐8. [PUBMED: 7542831] - PubMed
    1. Filteau SM, Morris SS, Tomkins AM, Arthur P, Kirkwood BR, Ross DA, et al. Lack of association between vitamin A status and measures of conjunctival epithelial integrity in young children in northern Ghana. European Journal of Clinical Nutrition 1994;48(9):669‐77. [PUBMED: 8001524] - PubMed
Ross 1993 SURVIVAL {published data only}
    1. Benn CS, Aaby P, Nielsen J, Binka FN, Ross DA. Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial. American Journal of Clinical Nutrition 2009;90(3):629‐39. [PUBMED: 19640958] - PubMed
    1. Binka FN, Ross DA, Morris SS, Kirkwood BR, Arthur P, Dollimore N, et al. Vitamin A supplementation and childhood malaria in northern Ghana. American Journal of Clinical Nutrition 1995;61(4):853‐9. [PUBMED: 7702031] - PubMed
    1. Dollimore N, Cutts F, Binka FN, Ross DA, Morris SS, Smith PG. Measles incidence, case fatality, and delayed mortality in children with or without vitamin A supplementation in rural Ghana. American Journal of Epidemiology 1997;146(8):646‐54. [PUBMED: 9345118] - PubMed
    1. Filteau SM, Morris SS, Raynes JG, Arthur P, Ross DA, Kirkwood BR, et al. Vitamin A supplementation, morbidity, and serum acute‐phase proteins in young Ghanaian children. American Journal of Clinical Nutrition 1995;62(2):434‐8. [PUBMED: 7542831] - PubMed
    1. Filteau SM, Morris SS, Tomkins AM, Arthur P, Kirkwood BR, Ross DA, et al. Lack of association between vitamin A status and measures of conjunctival epithelial integrity in young children in northern Ghana. European Journal of Clinical Nutrition 1994;48(9):669‐77. [PUBMED: 8001524] - PubMed
Semba 1991 {published data only}
    1. Semba R, Muhilal, Scott A, Natadisastra G, Wirasasmita S, Griffin D, et al. Immune status in children with mild vitamin A deficiency in Indonesia. Investigative Ophthalmology and Visual Science. Investigative Ophthalmology and Visual Science, Annual Meeting; 1991 April 28 ‐ May 3; Sarasota, FL. 1991; Vol. 32 (4).
    1. Semba RD, Muhilal MPH, West KP Jr, Winget M, Natadisastra G, Scott A, et al. Impact of vitamin A supplementation on hematological indicators of iron metabolism and protein status in children. Nutrition Research 1992;12(4‐5):469‐78. [DOI: 10.1016/S0271-5317(05)80017-X] - DOI
    1. Semba RD, Muhilal, Scott AL, Natadisastra G, West KP Jr, Sommer A. Effect of vitamin A supplementation on immunoglobulin G subclass responses to tetanus toxoid in children. Clinical and Diagnostic Laboratory Immunology 1994;1(2):172‐5. [PUBMED: 7496940] - PMC - PubMed
    1. Semba RD, Muhilal, Scott AL, Natadisastra G, Wirasasmita S, Mele L, et al. Depressed immune response to tetanus in children with vitamin A deficiency. Journal of Nutrition 1992;122(1):101‐7. [PUBMED: 1729457] - PubMed
Semba 1995 {published data only}
    1. Semba RD, Munasir Z, Beeler J, Akib A, Muhilal, Audet S, et al. Reduced seroconversion to measles in infants given vitamin A with measles vaccination. Lancet 1995;345(8961):1330‐2. [PUBMED: 7752754] - PubMed
Sempertegui 1999 {published data only}
    1. Sempértegui F, Estrella B, Camaniero V, Betancourt V, Izurieta R, Ortiz W, et al. The beneficial effects of weekly low‐dose vitamin A supplementation on acute lower respiratory infections and diarrhea in Ecuadorian children. Pediatrics 1999;104(1):e1. [PUBMED: 10390287] - PubMed
Shankar 1999 {published data only}
    1. Shankar AH, Genton B, Semba RD, Baisor M, Paino J, Tamja S, et al. Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised trial. Lancet 1999;354(9174):203‐9. [DOI: 10.1016/S0140-6736(98)08293-2] - DOI - PubMed
Sinha 1976 {published data only}
    1. Sinha DP, Bang FB. The effect of massive doses of vitamin A on the signs of vitamin A deficiency in preschool children. American Journal of Clinical Nutrition 1976;29(1):110‐5. [PUBMED: 1082238] - PubMed
Smith 1999 {published data only}
    1. Smith JC, Makdani D, Hegar A, Rao D, Douglass LW. Vitamin A and zinc supplementation of preschool children. Journal of the American College of Nutrition 1999;18(3):213‐22. [PUBMED: 10376776] - PubMed
Sommer 1986 {published data only}
    1. Abdeljaber MH, Monto AS, Tilden RL, Schork MA, Tarwotjo I. The impact of vitamin A supplementation on morbidity: a randomized community intervention trial. American Journal of Public Health 1991;81(12):1654‐6. [PMC1405285; PUBMED: 1746667] - PMC - PubMed
    1. Djunaedi E, Sommer A, Pandji A, Kusdiono, Taylor HR. Impact of vitamin A supplementation on xerophthalmia. A randomized controlled community trial. Archives of Ophthalmology 1988;106(2):218‐22. [PUBMED: 3277608] - PubMed
    1. Schmitz J, West KP Jr, Khatry SK, Wu L, LeClerq SC, Karna S, et al. Vitamin A supplementation in preschool children and risk of hearing loss as adolescents and young adults in rural Nepal: randomised trial cohort follow‐up study. BMJ 2012;344:d7962. [DOI: 10.1136/bmj.d7962] - DOI - PMC - PubMed
    1. Sommer A, Tarwotjo I, Djunaedi E, West KP Jr, Loeden AA, Tilden R, et al. Impact of vitamin A supplementation on childhood mortality. A randomised controlled community trial. Lancet 1986;1(8491):1169‐73. [PUBMED: 2871418] - PubMed
    1. Tielsch JM, West KP Jr. Cost and efficiency considerations in community‐based trials of vitamin A in developing countries. Statistics in Medicine 1990; Vol. 9, issue 1‐2:35‐41; discussion 41‐3. [PUBMED: 2345837] - PubMed
Stabell 1995 {published data only}
    1. Stabell C, Balé C, Pedro da Silva A, Olsen J, Aaby P. No evidence of fontanelle‐bulging episodes after vitamin A supplementation of 6‐ and 9‐month‐old infants in Guinea Bissau. European Journal of Clinical Nutrition 1995;49(1):73‐4. [PUBMED: 7713054] - PubMed
Stansfield 1993 {published data only}
    1. Stansfield SK, Pierre‐Louis M, Augustin A, Lerebours G. Vitamin A supplementation and increased prevalence of childhood diarrhoea and acute respiratory infections. Lancet 1993;342(8871):578‐82. [DOI: 10.1016/0140-6736(93)91410-N] - DOI - PubMed
Van Agtmaal 1988 {published data only}
    1. Agtmaal EJ, Bloem MW, Speek AJ, Saowakontha S, Schreurs HP, Haeringen NJ. The effect of vitamin A supplementation on tear fluid retinol levels of marginally nourished preschool children. Current Eye Research 1988;7(1):43‐8. [PUBMED: 3359804] - PubMed
Venkatarao 1996 {published data only}
    1. Venkatarao T, Ramakrishnan R, Nair NG, Radhakrishnan S, Sundaramoorthy L, Koya PK, et al. Effect of vitamin A supplementation to mother and infant on morbidity in infancy. Indian Pediatrics 1996; Vol. 33, issue 4:279‐86. [PUBMED: 8772901] - PubMed
Vijayaraghavan 1990 {published data only}
    1. Vijayaraghavan K, Radhaiah G, Surya Prakasam BS, Sarma KVR, Reddy V. Effect of massive dose vitamin A on morbidity and mortality in Indian children. Lancet 1990;336(8727):1342‐5. [PUBMED: 1978164] - PubMed
West 1991 {published data only}
    1. Bishai D, Kumar KCS, Waters H, Koenig M, Katz J, Khatry SK, et al. The impact of vitamin A supplementation on mortality inequalities among children in Nepal. Health Policy and Planning 2005;20(1):60‐6. [PUBMED: 15689431] - PubMed
    1. Katz J, West KP Jr, Khatry SK, Thapa MD, LeClerq SC, Pradhan EK, et al. Impact of vitamin A supplementation on prevalence and incidence of xerophthalmia in Nepal. Investigative Ophthalmology and Visual Science 1995;36(13):2577‐83. [PUBMED: 7499080] - PubMed
    1. Pokhrel RP, Khatry SK, West KP Jr, Shrestha SR, Katz J, Pradhan EK, et al. Sustained reduction in child mortality with vitamin A in Nepal. Lancet 1994;343(8909):1368‐9. [DOI: 10.1016/S0140-6736(94)92508-9] - DOI - PubMed
    1. Shih JH, Lu SE. Analysis of failure time data with multilevel clustering, with application to the child vitamin a intervention trial in Nepal. Biometrics 2007; Vol. 63, issue 3:673‐80. [PUBMED: 17825001] - PubMed
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References to studies excluded from this review

Al‐Mekhlafi 2014 {published data only}
    1. Al‐Mekhlafi HM, Al‐Zabedi EM, Al‐Maktari MT, Atroosh WM, Al‐Delaimy AK, Moktar N, et al. Effects of vitamin A supplementation on iron status indices and iron deficiency anaemia: a randomized controlled trial. Nutrients 2014;6(1):190‐206. [DOI: 10.3390/nu6010190; PMC3916855] - DOI - PMC - PubMed
    1. Al‐Mekhlafi HM, Anuar TS, Al‐Zabedi EM, Al‐Maktari MT, Mahdy MAK, Ahmed A, et al. Does vitamin A supplementation protect schoolchildren from acquiring soil‐transmitted helminthiasis? A randomized controlled trial. Parasites & Vectors 2014;7:367. [DOI: 10.1186/1756-3305-7-367] - DOI - PMC - PubMed
Bahl 1997 {published data only}
    1. Bahl R, Bhandari N, Taneja S, Bhan MK. The impact of vitamin A supplementation on physical growth of children is dependent on season. European Journal of Clinical Nutrition 1997; Vol. 51, issue 1:26‐9. [PUBMED: 9023463] - PubMed
Bhaskaram 1997 {published data only}
    1. Bhaskaram P, Rao KV. Enhancement in seroconversion to measles vaccine with simultaneous administration of vitamin A in 9‐months‐old Indian infants. Indian Journal of Pediatrics 1997;64(4):503‐9. [PUBMED: 10771879] - PubMed
Bloem 1990 {published data only}
    1. Bloem MW, Wedel M, Agtmaal EJ, Speek AJ, Saowakontha S, Schreurs WHP. Vitamin A intervention: short‐term effects of a single, oral, massive dose on iron metabolism. American Journal of Clinical Nutrition 1990;51(1):76‐9. [PUBMED: 2296931] - PubMed
Chen 2012 {published data only}
    1. Chen K, Li TY, Chen L, Qu P, Liu YX. Effects of vitamin A, vitamin A plus iron and multiple micronutrient‐fortified seasoning powder on preschool children in a suburb of Chongqing, China. Journal of Nutritional Science and Vitaminology 2008;54(6):440‐7. [PUBMED: 19155581] - PubMed
    1. Chen K, Liu YF, Chen L, Zhang X, Liu YX, Chen J, et al. Effects of vitamin A, vitamin A plus iron and multiple micronutrient‐fortified seasoning powder on iron metabolic homeostasis. Chinese Journal of Pediatrics 2011;49(12):926‐32. [PUBMED: 22336361] - PubMed
    1. Chen L, Liu YF, Gong M, Jiang W, Fan Z, Qu P, et al. Effects of vitamin A, vitamin A plus zinc, and multiple micronutrients on anemia in preschool children in Chongqing, China. Asia Pacific Journal of Clinical Nutrition 2012;21(1):3‐11. [PUBMED: 22374555] - PubMed
Chhagan 2010 {published data only}
    1. Chhagan MK, Broeck J, Luabeya KK, Mpontshane N, Tomkins A, Bennish ML. Effect on longitudinal growth and anemia of zinc or multiple micronutrients added to vitamin A: a randomized controlled trial in children aged 6‐24 months. BMC Public Health 2010;10:145. [DOI: 10.1186/1471-2458-10-145] - DOI - PMC - PubMed
    1. Chhagan MK, Broeck J, Luabeya KK, Mpontshane N, Tucker KL, Bennish ML. Effect of micronutrient supplementation on diarrhoeal disease among stunted children in rural South Africa. European Journal of Clinical Nutrition 2009;63(7):850‐7. [PUBMED: 19174830] - PMC - PubMed
Edmond 2012 {published data only}
    1. Edmond KL, Hurt L, Fenty J, Amenga‐Etego S, Zandoh C, Hurt C, et al. Effect of vitamin A supplementation in women of reproductive age on cause‐specific early and late infant mortality in rural Ghana: ObaapaVitA double‐blind, cluster‐randomised, placebo‐controlled trial. BMJ Open 2012;2(1):1‐10. [DOI: 10.1136/bmjopen-2011-000658] - DOI - PMC - PubMed
Fahmida 2007 {published data only}
    1. Fahmida U, Rumawas JSP, Utomo B, Patmonodewo S, Schultink W. Zinc‐iron, but not zinc‐alone supplementation, increased linear growth of stunted infants with low haemoglobin. Asia Pacific Journal of Clinical Nutrition 2007;16(2):301‐9. [PUBMED: 17468087] - PubMed
Ganon 2014 {published data only}
    1. Gannon B, Kaliwile C, Arscott SA, Schmaelzle S, Chileshe J, Kalungwana N, et al. Biofortified orange maize is as efficacious as a vitamin A supplement in Zambian children even in the presence of high liver reserves of vitamin A: a community‐based, randomized placebo‐controlled trial. American Journal of Clinical Nutrition 2014;100(6):1541‐50. [PUBMED: 25411289] - PMC - PubMed
Kartasurya 2012 {published data only}
    1. Kartasurya MI, Ahmed F, Subagio HW, Rahfiludin MZ, Marks GC. Zinc combined with vitamin A reduces upper respiratory tract infection morbidity in a randomised trial in preschool children in Indonesia. British Journal of Nutrition 2012;108(12):2251‐60. [PUBMED: 22414819] - PubMed
Kothari 1991 {published data only}
    1. Kothari G. The effect of vitamin A prophylaxis on morbidity and mortality among children in urban slums in Bombay. Journal of Tropical Pediatrics 1991;37(3):141. [PUBMED: 1861286] - PubMed
Nankabirwa 2011 {published data only}
    1. Nankabirwa V, Tylleskar T, Nankunda J, Engebretsen I, Sommerfelt H, Tumwine J. Poster presentation: prevalence of malaria parasitaemia among infants in Uganda and its association with breastfeeding, peer counselling and vitamin a supplementation. Tropical Medicine & International Health. Abstracts of the 7th European Congress on Tropical Medicine and International Health; 2011 October 3‐6; Barcelona, Spain. 2011; Vol. 16 Suppl s1:97.
    1. Nankabirwa V, Tylleskar T, Nankunda J, Engebretsen IM, Sommerfelt H, Tumwine JK. Malaria parasitaemia among infants and its association with breastfeeding peer counselling and vitamin A supplementation: a secondary analysis of a cluster randomized trial. PLOS ONE 2011;6(7):e21862. [PUBMED: 21760916] - PMC - PubMed
Owusu‐Agyei 2013 {published data only}
    1. Owusu‐Agyei SS, Newton E, Mahama LG, Febir M, Ali K, Adjei K, et al. Impact of vitamin A with zinc supplementation on malaria morbidity in Ghana. Nutrition Journal 2013;12:1‐9. [DOI: 10.1186/1475-2891-12-131] - DOI - PMC - PubMed
Semba 1990 {published data only}
    1. Semba RD, Wirasasmita S, Natadisastra G, Muhilal, Sommer A. Response of Bitot's spots in preschool children to vitamin A treatment. American Journal of Ophthalmology 1990;110(4):416‐20. [PUBMED: 2220978] - PubMed
Semba 2005 {published data only}
    1. Semba RD, Ndugwa C, Perry RT, Clark TD, Jackson JB, Melikian G, et al. Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus‐infected children in Uganda: a controlled clinical trial. Nutrition 2005;21(1):25‐31. [PUBMED: 15661475] - PubMed
Wu 2007 {published data only}
    1. Wu Z, Lin L, Ouyang L. Impact of vitamin A on the immune function of infants. China Tropical Medicine 2007;7(4):540‐1.
Yakymenko 2011 {published data only}
    1. Yakymenko D, Benn CS, Martins C, Diness BR, Fisker AB, Rodrigues A, et al. The impact of different doses of vitamin A supplementation on male and female mortality. A randomised trial from Guinea‐Bissau. BMC Pediatrics 2011;11:77. [DOI: 10.1186/1471-2431-11-77] - DOI - PMC - PubMed
Yang 2002 {published data only}
    1. Yang YX, Han JH, Shao XP, He M, Bian LH, Wang Z, et al. Effect of micronutrient supplementation on the growth of preschool children in China. Biomedical and Environmental Sciences 2002;15(3):196‐202. [PUBMED: 12500659] - PubMed

References to studies awaiting assessment

Aklamati 2006 {published data only}
    1. Aklamati E, Brown KH, Mulenga M, Kafwembe E, Peerson JM, Stephensen C, et al. Impact of high‐dose vitamin A supplements on vitamin A status of 3‐4 year old Zambian boys. FASEB Journal 2006;20(5):A1050.

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