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Meta-Analysis
. 2022 Mar 16;3(3):CD008524.
doi: 10.1002/14651858.CD008524.pub4.

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 , Maya R Haykal  3 , Allison Regan  3 , Jasleen Sidhu  3 , Abigail Smith  4 , Zulfiqar A Bhutta  5
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. .

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 (VAS) for children aged 6 to 59 months. The last version of this review was published in 2017, and this is an updated version of that review.

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: We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers up to March 2021. 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 review authors independently assessed studies for inclusion 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: The updated search identified no new RCTs. We identified 47 studies, involving approximately 1,223,856 children. Studies were set 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 studies included equal numbers of girls and boys and lasted about one year. The mean age of the children was about 33 months. 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 VAS compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-certainty evidence). 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 children; high-certainty evidence). There was no evidence of a difference for VAS on mortality due to measles (RR 0.88, 95% CI 0.69 to 1.11; 6 studies, 1,088,261 children; low-certainty evidence), respiratory disease (RR 0.98, 95% CI 0.86 to 1.12; 9 studies, 1,098,538 children; low-certainty evidence), and meningitis. VAS reduced the incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies, 77,946 children; low-certainty evidence), measles (RR 0.45, 95% CI 0.30 to 0.69; 2 studies, 1,982 children; low-certainty evidence), Bitot's spots (RR 0.42, 95% CI 0.33 to 0.53; 5 studies, 1,063,278 children; moderate-certainty evidence), night blindness (RR 0.32, 95% CI 0.21 to 0.50; 2 studies, 22,972 children; moderate-certainty evidence), and VAD (RR 0.71, 95% CI 0.65 to 0.78; 4 studies, 2262 children, moderate-certainty evidence). However, there was no evidence of a difference on incidence of respiratory disease (RR 0.99, 95% CI 0.92 to 1.06; 11 studies, 27,540 children; low-certainty evidence) 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 children; moderate-certainty evidence).

Authors' conclusions: This update identified no new eligible studies and the conclusions remain the same. VAS is associated with a clinically meaningful reduction in morbidity and mortality in children. 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 VAD, it would be unethical to conduct placebo-controlled trials.

Trial registration: ClinicalTrials.gov NCT03383744.

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Conflict of interest statement

AI: reported that he has no conflicts of interest.

EMW: reported that he has no conflicts of interest.

MH: reported that she has no conflicts of interest.

AR: reported that she has no conflicts of interest.

JS: reported that she has no conflicts of interest.

AS: reported that she has no conflicts of interest.

ZB: reported that he has no conflicts of interest.

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

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Rahman 2001 {published data only}
    1. Rahman MM, Tofail F, Wahed MA, Fuchs GJ, Baqui AH, Alvarez JO. Short-term supplementation with zinc and vitamin A has no significant effect on the growth of undernourished Bangladeshi children. American Journal of Clinical Nutrition 2002;75(1):87-91. [PMID: 10.1093/ajcn/75.1.87] - DOI - PubMed
    1. Rahman MM, Vermund SH, Wahed MA, Fuchs GJ, Baqui AH, Alvarez JO. Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial. BMJ 2001;323(7308):314-8. [DOI: 10.1136/bmj.323.7308.314] [PMCID: PMC37318] [PMID: ] - DOI - PMC - PubMed
    1. Rahman MM, Wahed MA, Fuchs GJ, Baqui AH, Alvarez JO. Synergistic effect of zinc and vitamin A on the biochemical indexes of vitamin A nutrition in children. American Journal of Clinical Nutrition 2002;75(1):92-8. [DOI: 10.1093/ajcn/75.1.92] [PMID: ] - DOI - PubMed
Rahmathullah 1990 {published data only}
    1. Acharya SK. Vitamin A supplementation reduces childhood mortality. National Medical Journal of India 1991;4(4):187-9. [PMID: ] - PubMed
    1. Rahmathullah L, Underwood BA, Thulasiraj RD, Milton RC, Ramaswamy K, Rahmathullah R, et al. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. New England Journal of Medicine 1990;323(14):929-35. [DOI: 10.1056/NEJM199010043231401] [PMID: ] - DOI - PubMed
    1. Rahmathullah L, Underwood BA, Thulasiraj RD, Milton RC. Diarrhea, respiratory infections, and growth are not affected by a weekly low-dose vitamin A supplement: a masked, controlled field trial in children in southern India. American Journal of Clinical Nutrition 1991;54(3):568-77. [DOI: 10.1093/ajcn/54.3.568] [PMID: ] - DOI - PubMed
    1. Rahmathullah L. Effect of receiving a weekly dose of vitamin A equivalent to the recommended dietary allowances among pre school children on mortality in south India. Indian Journal of Pediatrics 1991;58(6):837-47. [DOI: 10.1007/BF02825447] [PMID: ] - DOI - PubMed
Ramakrishnan 1995 {published data only}
    1. Ramakrishnan U, Latham MC, Abel R, Frongillo EA Jr. Vitamin A supplementation and morbidity among preschool children in south India. American Journal of Clinical Nutrition 1995;61(6):1295-303. [DOI: 10.1093/ajcn/61.6.1295] [PMID: ] - DOI - PubMed
    1. Ramakrishnan U, Latham MC, Abel R. Vitamin A supplementation does not improve growth of preschool children: a randomized, double-blind field trial in south India. Journal of Nutrition 1995;125(2):202-11. [DOI: 10.1093/jn/125.2.202] [PMID: ] - DOI - PubMed
Reddy 1986a {published data only}
    1. Reddy V, Vijayaraghavan K, Mathur KK. Effect of deworming and vitamin A administration on serum vitamin A levels in preschool children. Journal of Tropical Pediatrics 1986;32(4):196-9. [DOI: 10.1093/tropej/32.4.196] [PMID: ] - DOI - PubMed
Reddy 1986b {published data only}
    1. Reddy V, Vijayaraghavan K, Mathur KK. Effect of deworming and vitamin A administration on serum vitamin A levels in preschool children. Journal of Tropical Pediatrics 1986;32(4):196-9. [DOI: 10.1093/tropej/32.4.196] [PMID: ] - DOI - PubMed
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. [DOI: 10.3945/ajcn.2009.27477] [PMID: ] - DOI - 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. [DOI: 10.1093/ajcn/61.4.853] [PMID: ] - DOI - 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. [DOI: 10.1093/oxfordjournals.aje.a009330] [PMID: ] - DOI - 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. [DOI: 10.1093/ajcn/62.2.434] [PMID: ] - DOI - 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. [PMID: ] - 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. [DOI: 10.3945/ajcn.2009.27477] [PMID: ] - DOI - 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. [DOI: 10.1093/ajcn/61.4.853] [PMID: ] - DOI - 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. [DOI: 10.1093/oxfordjournals.aje.a009330] [PMID: ] - DOI - 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. [DOI: 10.1093/ajcn/62.2.434] [PMID: ] - DOI - 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. [PMID: ] - 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 1991;32(4):-. [URL: iovs.arvojournals.org/article.aspx?articleid=2178555]
    1. Semba RD, Muhilal MP, 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. [DOI: 10.1128/cdli.1.2.172-175.1994] [PMCID: PMC368222] [PMID: ] - DOI - 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. [DOI: 10.1093/jn/122.1.101] [PMID: ] - DOI - 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. [DOI: 10.1016/s0140-6736(95)92536-8] [PMID: ] - DOI - PubMed
Sempértegui 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. [DOI: 10.1542/peds.104.1.e1] [PMID: ] - DOI - 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] [PMID: ] - 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. [DOI: 10.1093/ajcn/29.1.110] [PMID: ] - DOI - 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. [DOI: 10.1080/07315724.1999.10718854] [PMID: ] - DOI - 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. [DOI: 10.2105/ajph.81.12.1654] [PMCID: PMC1405285] [PMID: ] - DOI - 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. [DOI: 10.1001/archopht.1988.01060130228033] [PMID: ] - DOI - 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] [PMCID: PMC3254201] [PMID: ] - 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. [DOI: 10.1016/s0140-6736(86)91157-8] [PMID: ] - DOI - 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;9(1-2):35-41; discussion 41-3. [DOI: 10.1002/sim.4780090110] [PMID: ] - DOI - 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. [PMID: ] - PubMed
Stansfield 1993 {published data only}
    1. Stansfield SK, Pierre-Louis M, Lerebours G, Augustin A. 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] [PMID: ] - 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. [DOI: 10.3109/02713688809047018] [PMID: ] - DOI - 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;33(4):279-86. [PMID: ] - PubMed
Vijayaraghavan 1990 {published data only}
    1. Vijayaraghavan K, Radhaiah G, Prakasam BS, Sarma KV, Reddy V. Effect of massive dose vitamin A on morbidity and mortality in Indian children. Lancet 1990;336(8727):1342-5. [DOI: 10.1016/0140-6736(90)92895-o] [PMID: ] - DOI - PubMed
West 1991 {published data only}
    1. Bishai D, Kumar KC, 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. [PMID: 10.1093/heapol/czi007] - DOI - 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. [PMID: ] - 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] [PMID: ] - 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;63(3):673-80. [DOI: 10.1111/j.1541-0420.2007.00756.x] [PMID: ] - DOI - PubMed
    1. West KP Jr, LeClerq SC, Shrestha SR, Wu LS, Pradhan EK, Khatry SK, et al. Effects of vitamin A on growth of vitamin A-deficient children: field studies in Nepal. Journal of Nutrition 1997;127(10):1957-65. [DOI: 10.1093/jn/127.10.1957] [PMID: ] - DOI - PubMed

References to studies excluded from this review

Ahmad 2020 {published data only}
    1. Ahmad SM, Huda MN, Raqib R, Qadri F, Alam MJ, Afsar MN, et al. High-dose neonatal vitamin A supplementation to Bangladeshi infants increases the percentage of CCR9-positive Treg cells in infants with lower birthweight in early infancy, and decreases plasma sCD14 concentration and the prevalence of vitamin A deficiency at two years of age. Journal of Nutrition 2020;150(11):3005-12. [DOI: 10.1093/jn/nxaa260] [PMCID: PMC7675026 (available on 2021-09-16)] [PMID: ] - DOI - PMC - PubMed
Ali 2017 {published data only}
    1. Ali H, Hamadani J, Mehra S, Tofail F, Hasan MI, Shaikh S, et al. Effect of maternal antenatal and newborn supplementation with vitamin A on cognitive development of school-aged children in rural Bangladesh: a follow-up of a placebo-controlled, randomized trial. American Journal of Clinical Nutrition 2017;106(1):77-87. [DOI: 10.3945/ajcn.116.134478] [PMID: ] - DOI - PubMed
Al‐Mekhlafi 2013 {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 2013;6(1):190-206. [DOI: 10.3390/nu6010190] [PMCID: PMC3916855] [PMID: ] - DOI - PMC - PubMed
    1. Al-Mekhlafi HM, Anuar TS, Al-Zabedi EM, Al-Maktari MT, Mahdy MA, 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] [PMCID: PMC4141119] [PMID: ] - 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;51(1):26-9. [DOI: 10.1038/sj.ejcn.1600352] [PMID: ] - DOI - PubMed
Basu 2019 {published data only}
    1. Basu S, Khanna P, Srivastava R, Kumar A. Oral vitamin A supplementation in very low birth weight neonates: a randomized controlled trial. European Journal of Pediatrics 2019;178(8):1255-65. - PubMed
Benn 2017 {published data only}
    1. Benn CS, Fisker AB, Aaby P. Serious danger signals: response to: the effect of neonatal vitamin A supplementation on morbidity and mortality at 12 months: a randomized trial. International Journal of Epidemiology 2017;46(5):1718-20. [DOI: 10.1093/ije/dyx139] [PMID: ] - DOI - PubMed
Berde 2019 {published data only}
    1. Berde AS, Bester P, Kruger IM. Coverage and factors associated with vitamin A supplementation among children aged 6–59 months in twenty-three sub-Saharan African countries. Public Health Nutrition 2019;22(10):1770-6. [DOI: 10.1017/S1368980018004056] [PMID: ] - DOI - PMC - 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. [DOI: 10.1007/BF02737757] [PMID: ] - DOI - PubMed
Bhattacharya 2017 {published data only}
    1. Bhattacharya S, Singh A. Time to revisit the strategy of massive vitamin A prophylaxis dose administration to the under five children in India – an analysis of available evidence. Clinical Nutrition ESPEN 2017;21:26-30. [DOI: 10.1016/j.clnesp.2017.07.001] [PMID: ] - DOI - PubMed
Bloem 1990 {published data only}
    1. Bloem MW, Wedel M, Agtmaal EJ, Speek AJ, Saowakontha S, Schreurs WH. 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. [DOI: 10.1093/ajcn/51.1.76] [PMID: ] - DOI - PubMed
Changezi 2017 {published data only}
    1. Changezi F, Lindberg L. Socio-economic determinants of vitamin A intake in children under 5 years of age: evidence from Pakistan. Journal of Human Nutrition and Dietetics 2017;30(5):615-20. [DOI: 10.1111/jhn.12450] [PMID: ] - DOI - 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. [DOI: 10.3177/jnsv.54.440] [PMID: ] - DOI - 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. [PMID: ] - 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. [PMID: ] - PubMed
Chen 2016 {published data only}
    1. Chen K, Xie HM, Tian W, Zheng X, Jiang AC. Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China. British Journal of Nutrition 2016;115(8):1415-23. [DOI: 10.1017/S0007114516000350] [PMID: ] - DOI - PubMed
Chhagan 2009 {published data only}
    1. Chhagan MK, den 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] [PMCID: PMC2847544] [PMID: ] - DOI - PMC - PubMed
    1. Chhagan MK, den 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. [DOI: 10.1038/ejcn.2008.78] [PMCID: PMC2705811] [PMID: ] - DOI - PMC - PubMed
Clermont 2017 {published data only}
    1. Clermont A. The impact of eliminating within-country inequality in health coverage on maternal and child mortality: A Lives Saved Tool analysis. BMC Public Health 2017;17(Suppl 4):734. [DOI: 10.1186/s12889-017-4737-2] [PMCID: PMC5688502] [PMID: ] - DOI - 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):e000658. [DOI: 10.1136/bmjopen-2011-000658] [PMCID: PMC3330261] [PMID: ] - DOI - PMC - PubMed
Fahmida 2007 {published data only}
    1. Fahmida U, Rumawas JS, 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. [PMID: ] - PubMed
Gannon 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. [DOI: 10.3945/ajcn.114.087379] [PMCID: PMC4232019] [PMID: ] - DOI - PMC - PubMed
Guevara 2016 {published data only}
    1. Guevara D, Reyes S, Anarumba D, Lopez M, Cevallos S, Montenegro E, et al. Impact of milk based micronutrient supplementation on zinc, iron, and vitamin A deficiencies in school children in Quito-Ecuador. FASEB Journal 2016;30(Suppl 1):292.8. [DOI: 10.1096/fasebj.30.1_supplement.292.8] - DOI
Handjieva‐Darlenska 2014 {published data only}
    1. Handjieva-Darlenska T, Hristova K, Singh RB. Antioxidant vitamins and the heart. World Heart Journal 2014;6(3):179-84. [URL: www.researchgate.net/publication/286291843_Antioxidant_vitamins_and_the_...]
Handjieva‐Darlenska 2016 {published data only}
    1. Handjieva-Darlenska T, Hristova K, Singh RB. Antioxidant vitamins and the heart. Chronocardiology and Cardiac Research 2016;4:263-70.
Healy 2018 {published data only}
    1. Healy K, Palmer AC, Barffour MA, Schulze KJ, Siamusantu W, Chileshe J, et al. Nutritional status measures are correlated with pupillary responsiveness in Zambian children. Journal of Nutrition 2018;148(7):1160-6. [DOI: 10.1093/jn/nxy069] [PMID: ] - DOI - PubMed
Hoang 2021 {published data only}
    1. Hoang NT, Orellana L, Gibson RS, Le TD, Worsley A, Sinclair AJ, et al. Multiple micronutrient supplementation improves micronutrient status in primary school children in Hai Phong City, Vietnam: a randomised controlled trial. Scientific Reports 2021;11(1):3728. [DOI: ] [PMCID: PMC7881239] [PMID: ] - PMC - PubMed
Horton 2018 {published data only}
    1. Horton S, Blum LS, Diouf M, Ndiaye B, Ndoye F, Niang K, et al. Delivering vitamin A supplements to children aged 6–59 months: comparing delivery through campaigns and through routine health services in Senegal. Current Developments in Nutrition 2018;2(4):nzy006. [DOI: 10.1093/cdn/nzy006] [PMCID: PMC6041955] [PMID: ] - DOI - PMC - PubMed
Kahbazi 2019 {published data only}
    1. Kahbazi M, Sharafkhah M, Yousefichaijan P, Taherahmadi H, Rafiei M, Kaviani P, et al. Vitamin A supplementation is effective for improving the clinical symptoms of urinary tract infections and reducing renal scarring in girls with acute pyelonephritis: a randomized, double-blind placebo-controlled, clinical trial study. Complimentary Therapies in Medicine 2019;42:429-37. [DOI: 10.1016/j.ctim.2018.12.007] [PMID: ] - DOI - 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. [DOI: 10.1017/S0007114512000499] [PMID: ] - DOI - PubMed
Kartasurya 2020 {published data only}
    1. Kartasurya MI, Marks GC, Ahmed F, Subagio HW, Rahfiludin MZ. Effect of zinc and vitamin A supplementation on immune responses in Indonesian pre-schoolers. Asia Pacific Journal of Clinical Nutrition 2020;29(4):732-42. [DOI: 10.6133/apjcn.202012_29(4).0008] [PMID: ] - DOI - PubMed
Khan 2020 {published data only}
    1. Khan JR, Karim ME. A propensity score analysis of the effect of a single dose vitamin A supplementation on child hemoglobin status in Bangladesh. Child Care in Practice 2020. [DOI: 10.1080/13575279.2020.1837074] - DOI
Kheirkhah 2016 {published data only}
    1. Kheirkhah D, Sharif MR, Honarpisheh P, Sharif A. The effects of vitamin A on acute watery diarrhea in children 1–5 years old. International Journal of Medical Research & Health Sciences 2016;5(12):228-32. [URL: www.indianjournals.com/ijor.aspx?target=ijor:ijmrhs&volume=5&issue=12&ar...]
Koroma 2020 {published data only}
    1. Koroma AS, Conteh SG, Bah M, Kamara HI, Turay M, Kandeh A, et al. Routine vitamin A supplementation and other high impact interventions in Sierra Leone. Maternal & Child Nutrition 2020;16(4):e13041. [DOI: 10.1111/mcn.13041] [PMCID: PMC7507363] [PMID: ] - DOI - PMC - 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. [DOI: 10.1093/tropej/37.3.141] [PMID: ] - DOI - PubMed
Kranz 2017 {published data only}
    1. Kranz S, Pimpin L, Fawzi W, Duggan C, Webb P, Mozaffarian D. Mortality benefits of vitamin A are not affected by varying frequency, total dose, or duration of supplementation. Food and Nutrition Bulletin 2017;38(2):260-6. [DOI: 10.1177/0379572117696663] [PMID: ] - DOI - PubMed
Laillou 2021 {published data only}
    1. Laillou A, Baye K, Zelalem M, Chitekwe S. Vitamin A supplementation and estimated number of averted child deaths in Ethiopia: 15 years in practice (2005–2019). Maternal & Child Nutrition 2021;17(3):e13132. [DOI: 10.1111/mcn.13132] [PMCID: PMC8189216] [PMID: ] - DOI - PMC - PubMed
Lakshman 2011 {published data only}
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NCT04137354 {published data only}
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Oiye 2019 {published data only}
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References to studies awaiting assessment

Aklamati 2006 {published data only}
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References to other published versions of this review

Imdad 2010a
    1. Imdad A, Herzer K, Mayo-Wilson E, Yakoob MY, Bhutta ZA. Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age. Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No: CD008524. [DOI: 10.1002/14651858.CD008524.pub2] [PMID: ] - DOI - PubMed
Imdad 2010c
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Imdad 2017
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Publication types

Associated data