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14 years agoThis question is often asked and many are not aware of the basis of the recommendations. They come from the work of Phillipe Donnen. First published in abstract form the papers available - abstracts and refs are as follows: This is the original abstract: available from: DAILY LOW DOSES OF VITAMIN A COMPARED WITH SINGLE HIGH DOSE IMPROVES SURVIVAL OF MALNOURISHED CHILDREN IN SENEGAL. Ph Donnen, A Sylla, M Dramaix, G Sall, N Kuakuvi, Ph Hennart. Background: Vitamin A (VA) deficiency is widely prevalent in hospitalized malnourished children in less-developed countries and mortality rates are high. Recommendation to give high doses of VA to children suffering from severe malnutrition is not sustained by results of research. Small doses of VA given regularly during hospitalization might be a better strategy to improve mortality and morbidity. Aims: To assess the effect of daily low doses of vitamin A on hospitalized malnourished children's mortality and morbidity. Methods: We did a double-blind, randomized trial in 604 and 610 Senegalese hospitalized children. The first mentioned batch received a high dose VA supplement (200.000 IU) on admission, the second a daily low dose VA supplement (5.000 IU per day) during hospitalization. Children were followed up until discharged. All cases of mortality were recorded and data on all-causes morbidity were collected daily. Results: Children of both groups were similar at baseline in terms of age and nutritional status. Low serum retinol concentrations were found in more than 75% of the study sample. Mortality was 9.7% (59 deaths) in the low doses group and 11.1% (67 deaths) in the high dose group (NS). In children without oedema on admission, mortality was similar in both treatment groups. In children with oedema on admission, mortality was significantly lower in the low doses group (Adjusted odds ratio : 0.21 ; 95% CI : 0.05-0.99). The proportion of children who never presented acute respiratory infection during hospitalization was significantly higher in the low doses group (83.5 vs. 77.8, p=0.043) whereas the proportion of children who never presented diarrhoea was not significantly different among the two groups. Median percent time ill for acute respiratory infection and diarrhoea were not significantly different in the two groups. Conclusions: In hospitalized severely malnourished children, daily low doses of VA improved mortality better than a single high dose. There have now been two full papers published - one a full report of the Senegal study and the other from DRC: Donnen P, Sylla A, Dramaix M, Sall G, Kuakuvi N, Hennart P. Effect of daily low dose of vitamin A compared with single high dose on morbidity and mortality of hospitalized mainly malnourished children in senegal: a randomized controlled clinical trial. Eur J Clin Nutr 2007 December;61(12):1393-9. Abstract: BACKGROUND: In vitamin A-deficient populations, children hospitalized with infections and/or malnutrition are at particular risk of developing severe vitamin A (VA) deficiency. High-dose VA supplements are recommended as part of the treatment but results on its effect on recovery from morbidity and on prevention from nosocomial morbidity are conflicting. OBJECTIVE: We aimed to assess the effect of a single high dose and daily low dose of VA on hospitalized malnourished children's morbidity. DESIGN: We carried out a double-blind, randomized trial in 604 and 610 Senegalese hospitalized children. The first mentioned batch received a high-dose VA supplement (200,000 IU) on admission, the second a daily low-dose VA supplement (5000 IU per day) during hospitalization. Children were followed up until discharged. Data on all-cause morbidity were collected daily. RESULTS: Survival analysis showed that the incidence of respiratory disease was significantly lower in the low-dose group than in the high-dose group, hazard ratios (HR): 0.26, 95% CI: 0.07-0.92. The duration of respiratory infection was also significantly lower in the low-dose group than in the high-dose group (HR of cure: 1.41, 95% CI: 1.05-1.89). Duration and incidence of diarrhoea were not significantly different between treatment groups. In children with oedema on admission, mortality was significantly lower in the low-dose group (Adjusted odds ratio: 0.21; 95% CI: 0.05-0.99). CONCLUSIONS: Daily low dose of VA compared with single high dose significantly reduced duration and incidence of respiratory infection but not of diarrhoea in hospitalized children Donnen P, Dramaix M, Brasseur D, Bitwe R, Vertongen F, Hennart P. Randomized placebo-controlled clinical trial of the effect of a single high dose or daily low doses of vitamin A on the morbidity of hospitalized, malnourished children. Am J Clin Nutr 1998 December;68(6):1254-60. Abstract: The effect of high-dose vitamin A supplementation on recovery from morbidity and on recovery from nosocomial morbidity of hospitalized children has been poorly studied and results are conflicting. The effect of daily, low doses has never been assessed. We investigated the effect of a single high dose and daily, low doses of vitamin A on diarrhea, acute lower respiratory tract infections (ALRIs), and all-cause fevers in 900 hospitalized preschool-age children in the Democratic Republic of Congo in a randomized, double-blind, placebo-controlled clinical trial. The high-dose treatment group received 200,000 IU vitamin A (100,000 IU if aged <12 mo) orally on the day of admission, the low-dose treatment group received 5000 IU vitamin A/d until discharge. Data on all-cause morbidity were collected daily. Mortality rates were not significantly different among the 3 groups. High-dose vitamin A supplementation had no significant effect on the duration of moderate or severe diarrhea nor on the duration and incidence of ALRIs and all-cause fevers. Children in the high-dose group with no edema had an increased risk of severe nosocomial diarrhea (relative risk: 2.42; 95% CI: 1.15, 5.11). Low-dose vitamin A supplementation significantly reduced the incidence of severe diarrhea in severely malnourished children (relative risk: 0.21; 95% CI: 0.07, 0.62) but showed no significant effect on the duration of moderate or severe diarrhea or on the duration and incidence of ALRIs and all-cause fevers. Supplementation with high doses of vitamin A did not reduce morbidity in this population of malnourished and subclinically vitamin A-deficient children; daily, low doses appeared more beneficial for severely malnourished children In Summary - in DRC the low dose group marasmic children had less severe diarrhoea (one fifth as much). In Senegal there was less RTI (one quarter) - the mortality rate was lower in the Oedematous children. It would seem that in both marasmic children and kwash there is no advantage in giving high dose vit A on admission and these RCTs show that there is likely to be a detrimental effect on diarrhoea and/or RTI and for the kwash children mortality. Thus, my current recommendations are: 1) if F100/F75/RUTF is being given then there is sufficient vitamin A already in these products to supply enough vitamin A for routine situations 2) where other products have to be used because of unavailability of the correct formulations then either vitamin A can be added to the formulation on a daily basis or capsules can be given. 3) Vitamin A capsules shoule continue to be given ON AN INDVIDUAL CHILD basis if there are: a) any clinical signs of vitamin A deficiency in that child. b) if the child has, or has been exposed to measles (or during a measles epidemic). Routine treatment with high doses could be extended to areas where there is a high prevalence of symptomatic vitamin A deficiency (now thankfully relatively rare) and possibily to areas were both vitamin A capsule distribution AND measles coverage are very low. These latter recommedations are likely to change as the subject is studied further. I addressed the possible mechanisms for this effect in a presentation to WHO some years ago. The main side effect of vit A overdose is increased cerebro-spinal fluid accumulation (pseudo-tumour cerebrae) - it would appear that large doses of Vit A can have an effect upon salt and water transport and this could affect electrolyte imbalance, particularly in Kwash - but the elucidation requires further studies in tissues, animals and man.
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10 years agomostly the vitamin A capsules are normally in 50,000,10,000 and 200,000 iu so how can one come up with 5000 iu?
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7 years agoI imagine that you want to use VA for frequent use in small doses. Ideally you would purchase from the normal suppliers by odering what you need but if this is not possible, do a calculation and then add only what is required for your intervention vehicle from the VA you have
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7 years agoThe 5000 IU/day of Vitamin A corresponds to the dose received on average by a child consuming the recommended amounts of F-75 and RUTF. See discussion above.
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7 years agowhy vitamin A is not given to infants having oedema ?
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6 years agoWhat is the physiological pathway that causes mortality following supplementation of vitamins in a malnourished child with oedema?
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5 years agoVitamin A supplementation is recognized as one of the most cost-effective interventions for improving child survival.
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3 years ago