The impact of different doses of vitamin A supplementation on male and female mortality. A randomised trial from Guinea-Bissau

Dorthe Yakymenko, Christine S Benn, Cesario Martins, Birgitte R Diness, Ane B Fisker, Amabelia Rodrigues, Peter Aaby, Dorthe Yakymenko, Christine S Benn, Cesario Martins, Birgitte R Diness, Ane B Fisker, Amabelia Rodrigues, Peter Aaby

Abstract

Background: Vitamin A supplementation (VAS) given to children between 6 months and 5 years of age is known to reduce mortality in low-income countries. We have previously observed that girls benefit more from a lower dose of VAS than the one recommended by WHO, the effect being strongest if diphtheria-tetanus-pertussis vaccine (DTP) was the most recent vaccination. We aimed to test these observations.

Methods: During national immunisations days in Guinea-Bissau, West Africa, combining oral polio vaccination and VAS, we randomised 8626 children between 6 months and 5 years of age to receive the dose of VAS recommended by WHO or half this dose. Mortality rate ratios (MRRs) were assessed after 6 and 12 month.

Results: The overall mortality rate among participants was lower than expected. There was no significant difference in mortality at 6 months and 12 months of follow up between the low dose VAS group and the recommended dose VAS group. The MRRs were 1.23 (0.60-2.54) after 6 months and 1.17 (0.73-1.87) after 12 months. This tendency was similar in boys and girls. The low dose was not associated with lower mortality in girls if the most recent vaccine was DTP (MRR = 0.60 (0.14-2.50) after 6 months).

Conclusion: Our sample size does not permit firm conclusions since mortality was lower than expected. We could not confirm a beneficial effect of a lower dose of VAS on mortality in girls.

Trial registration: The study was registered under clinicaltrials.gov, number NCT00168636.

Figures

Figure 1
Figure 1
Flow chart.
Figure 2
Figure 2
Kaplan-Meier survival curves in boys and girls, comparing participants with non-participants.

References

    1. Beaton GH, Martorell R, McCabe G, L'abbé KA, Edmonston B, Ross AC. Effectiveness of vitamin A supplementation in the control of young child morbidity and mortality in developing countries. University of Toronto. 1993.
    1. Fawzi WW, Chalmers TC, Herrera MG, Mosteller F. Vitamin A supplementation and child mortality. A meta-analysis. JAMA. 1993;269:898–903. doi: 10.1001/jama.269.7.898.
    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 Syst Rev. 2010. p. CD008524.
    1. WHO/UNISEF/IVAGG Task Force. Vitamin A supplement. A guide to their use in the treatment and prevention of vitamin A deficiency and xerophthalmia. Geneva, WHO. 1997.
    1. Kristensen I, Aaby P, Jensen H. Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ. 2000;321:1435–1438. doi: 10.1136/bmj.321.7274.1435.
    1. Aaby P, Samb B, Simondon F, Seck AM, Knudsen K, Whittle H. Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries. BMJ. 1995;311:481–485.
    1. Aaby P, Bhuiya A, Nahar L, Knudsen K, de FA, Strong M. The survival benefit of measles immunization may not be explained entirely by the prevention of measles disease: a community study from rural Bangladesh. Int J Epidemiol. 2003;32:106–116. doi: 10.1093/ije/dyg005.
    1. Garly ML, Martins CL, Bale C, Balde MA, Hedegaard KL, Gustafson P, Lisse IM, Whittle HC, Aaby P. BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG? Vaccine. 2003;21:2782–2790. doi: 10.1016/S0264-410X(03)00181-6.
    1. Aaby P, Jensen H, Gomes J, Fernandes M, Lisse IM. The introduction of diphtheria-tetanus-pertussis vaccine and child mortality in rural Guinea-Bissau: an observational study. Int J Epidemiol. 2004;33:374–380. doi: 10.1093/ije/dyh005.
    1. Benn CS, Bale C, Sommerfelt H, Friis H, Aaby P. Hypothesis: Vitamin A supplementation and childhood mortality: amplification of the non-specific effects of vaccines? Int J Epidemiol. 2003;32:822–828. doi: 10.1093/ije/dyg208.
    1. WHO/CHD Immunisation-Linked Vitamin A Supplementation Study Group. Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. Lancet. 1998;352:1257–1263.
    1. Benn CS, Martins C, Rodrigues A, Jensen H, Lisse IM, Aaby P. Randomised study of effect of different doses of vitamin A on childhood morbidity and mortality. BMJ. 2005;331:1428–1432. doi: 10.1136/bmj.38670.639340.55.
    1. Semba RD, Munasir Z, Akib A, Melikian G, Permaesih D, Muherdiyantiningsih, Marituti S, Muhilal. Integration of vitamin A supplementation with the Expanded Programme on Immunization: lack of impact on morbidity or infant growth. Acta Paediatr. 2001;90:1107–1111. doi: 10.1111/j.1651-2227.2001.tb03237.x.
    1. Rahmathullah L, Underwood BA, Thulasiraj RD, Milton RC, Ramaswamy K, Rahmathullah R, Babu G. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. N Engl J Med. 1990;323:929–935. doi: 10.1056/NEJM199010043231401.
    1. Standardized VA questionnaire (Revised August 2003) INDEPTH network. 2005.
    1. Benn CS, Diness BR, Roth A, Nante E, Fisker AB, Lisse IM, Yazdanbakhsh M, Whittle H, Rodrigues A, Aaby P. Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial. BMJ. 2008;336:1416–1420. doi: 10.1136/.
    1. Fisker AB, Aaby P, Rodrigues A, Frydenbeg M, Bibby BM, Benn CS. Vitamin A supplementation at birth primes the response to subsequent vitamin A supplements: A beneficial effect for girls. Accepted for PLoS ONE. 2011.
    1. Jensen H, Benn CS, Lisse IM, Rodrigues A, Andersen PK, Aaby P. Survival bias in observational studies of the impact of routine immunizations on childhood survival. Trop Med Int Health. 2007;12:5–14.
    1. Benn CS, Lund S, Fisker A, Jorgensen MJ, Aaby P. Should infant girls receive micronutrient supplements? Int J Epidemiol. 2009;38:586–590.
    1. Sommer A, Tarwotjo I, Djunaedi E, West KP Jr, Loeden AA, Tilden R, Mele L. Impact of vitamin A supplementation on childhood mortality. A randomised controlled community trial. Lancet. 1986;1:1169–1173.
    1. Humphrey JH, Agoestina T, Wu L, Usman A, Nurachim M, Subardja D, Hidayat S, Tielsch J, West KP Jr, Sommer A. Impact of neonatal vitamin A supplementation on infant morbidity and mortality. J Pediatr. 1996;128:489–496. doi: 10.1016/S0022-3476(96)70359-1.
    1. Benn CS, Fisker AB, Diness BR, Aaby P. Neonatal vitamin a supplementation: sex-differential effects on mortality? J Infect Dis. 2006;194:719. doi: 10.1086/506457.
    1. Benn CS, Rodrigues A, Yazdanbakhsh M, Fisker AB, Ravn H, Whittle H, Aaby P. The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination. Vaccine. 2009;27:2891–2898. doi: 10.1016/j.vaccine.2009.02.080.
    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. Am J Clin Nutr. 2009;90:629–639. doi: 10.3945/ajcn.2009.27477.
    1. Benn CS, Fisker AB, Napirna BM, Roth A, Diness BR, Lausch KR, Ravn H, Yazdanbakhsh M, Rodrigues A, Whittle H, Aaby P. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial. BMJ. 2010;340:c1101. doi: 10.1136/bmj.c1101.
    1. Fisker AB, Lisse IM, Aaby P, Erhardt JG, Rodrigues A, Bibby BM, Benn CS. Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age. Am J Clin Nutr. 2007;86:1032–1039.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel