SandfordSmith JH, The studies by Rosales and Ogaro were associated with no effect on the risk of mortality in the supplemented group. The study, led by the University of Tampere in Finland, is part of the long-term . Vitamin A supplementation has been shown to reduce morbidity and mortality due to measles in children in medically underserved areas. Kumar R, Xerophthalmia is a severe drying of the eye surface caused by a malfunction of the tear glands. In the first data collection round, information was obtained on whether each child had ever been hospitalized or had ever had measles. We will assess funnel plot asymmetry visually and use formal tests for funnel plot asymmetry. These are also the studies using two doses and showing a protective effect on measles mortality in the children treated with vitamin A. et al. Diarrhea Skin problems While vitamin A is essential for good health, it can be toxic in high doses. The measles vaccine isn't given to children until they're at least 12 months old. Ramaswamy K, Measles has been preventable since 1963 through vaccination. and as a result attenuates the therapeutic effect estimates for vitamin A treatment of measles. We used the following terms in MEDLINE and CENTRAL and adapted them for EMBASE. There was no significant reduction in the risk of mortality in the vitamin A group when all the studies were pooled (RR 0.70; 95% CI 0.42 to 1.15). 3 morbilli virus.tw. et al. At each round, information was obtained on illnesses within the past week, the child's weight, and left midupper arm circumference and, from the second dosing round, on hospitalization or measles since the last visit. A MEDLINE (PubMed) search was conducted in July 1999 (1994 to 1998). Vitamin A reduces the risk of death from measles by 87% for children younger than 2 years. Sension MG, The two studies (Ogaro 1993; Rosales 1996) that used an oilbased single dose of vitamin A (200,000 IU) were carried out in areas where the casefatality rate was less than 6% and were not associated with any reduction in the risk of mortality. Key facts Even though a safe and cost-effective vaccine is available, in 2018, there were more than 140 000 measles deaths globally, mostly among children under the age of five. In another metaanalysis of 12 controlled trials, including community preventative studies (Fawzi 1993), vitamin A supplementation for hospitalized measles participants (children) was found to be highly protective against mortality. Bhaskaram P, Federal government websites often end in .gov or .mil. Kumar L, All the Vitamin A supplements in the eight trials included in this review were administrated orally. The children in the Rosales (Rosales 1996) and Ogaro studies may not have benefited from receiving vitamin A oilbased preparations in a single dose (200,000 IU) as this might not have been sufficient to reverse the hyporetinemia occurring during measles; the dose may have been stored, mostly in the liver. We calculated mean differences (MDs) with 95% CIs for continuous outcomes using the randomeffects model. and transmitted securely. 7 exp Vitamin A/ Ogaro's study used a single dose of vitamin A and did not show any benefit either. Eight trials met the inclusion criteria (2574 participants). None of the studies included in this review reported any adverse effects. Dollimore used at least two doses of vitamin A and showed there was no significant difference in the risk of mortality in the community between vitamin Asupplemented and placebo groups. Measles can reduce serum concentrations of vitamin A in wellnourished children to levels less than those observed in malnourished children without measles (Inua 1983). In 1991, Rosales (Rosales 1996) came to the same conclusion as did Sommer, who suggested that it was prudent to follow the doubledose schedule already proven in the Barclay, Hussey and Coutsoudis trials rather than the single dose recommended by WHO at that time. 5 rubeola.tw. The highly sensitive search strategy was combined with the MEDLINE search strategy (Lefebvre 2011). 1. In Barclay's study (Barclay 1987) the staff and participants were blinded but not the treating physician who also assessed the outcomes. et al. Broughton M, In a number of community studies in Asia, vitamin A deficiency has been linked to an increased risk of childhood morbidity (Bloem 1990; Milton 1987; Sommer 1984) and mortality (Sommer 1983). The Nordic Cochrane Centre, The Cochrane Collaboration. Katz J, None of the studies included in this review reported any adverse effects. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. Although in South Africa the measles casefatality rate was greater than 10% in hospitals, Coutsoudis had low casefatality rates in both the vitamin A and control groups. [Skip to Navigation] Our website uses cookies to enhance your experience. All children should get 2 doses of the MMR vaccine to prevent measles. Measles is a major cause of childhood morbidity and mortality. Headaches, loss of appetite, vomiting and bulging fontanelles (in infants) are some of the known adverse effects occasionally occurring with the administration of high doses of vitamin A. Driskell WJ, In Barclay's study, which used two doses, there was a 65% reduction in risk of developing diarrhea while there was no evidence of reduction in Ogaro's study, which used a single dose. We carried out subgroup analyses for dose, formulation, age, hospitalization and pneumoniaspecific mortality. Coutsoudis (Coutsoudis 1991) found that the vitamin A group had a 1.5 times better chance of complete clinical recovery than the placebo group, which was statistically significant. Coutsoudis A, The level of immunization would have had an impact on the severity of measles as it could reduce the intensity of exposure and hence the dose of the infecting virus (Hussey 1997). The pooled estimate of these studies suggests the risk of pneumoniaspecific mortality (RR 0.57; 95% CI 0.24 to 1.37); none of these studies showed statistically significant reductions on their own. There was considerable variation in the outcomes measured and reported in the studies. Recommended doses are 30,000 mcg RAE (100,000 IU) of vitamin A once for . official website and that any information you provide is encrypted The study showed a statistically significant reduction by two days in the vitamin Atreated group (MD 2.00; 95% CI 2.71 to 1.29). In the current version of the review, however, there were not enough trials reporting on the same outcomes to present a meaningful analysis. Thulasiraj RD, Although the waterbased product may be associated with greater mortality reductions the advantage may be offset by its lower stability, higher cost and nonavailability. Only the Coutsoudis study indicated some longterm benefit of vitamin A as children were followed for six months; the outcomes used for this review were at the time of discharge from hospital. Cleveland Clinic is a non-profit academic medical center. Comparison 1 Vitamin A versus placebo, Outcome 3 Morbidity (continuous data). We have rounded these off to 98 and 107 per 1000 respectively. Sixtysix references were found using this search strategy. In four studies that reported large reductions in mortality, measles mortality fell but acute respiratory infection (ARI) mortality did not change (Daulaire 1992; Rahmathullah 1990; VAST Study 1993; West 1991). An absence of vitamin A effect, or a smaller effect, in the community studies (Dollimore 1997; Rosales 1996) may be due to the study populations being healthier than the studies in hospitals. Two studies (Coutsoudis 1991; Hussey 1990) reported the duration of diarrhea in days. Impact of vitamin A supplementation on childhood mortality. Only one study (Ellison 1932) received a score of less than three and we included this in the sensitivity analysis. Rahmathullah L, At least 2,188,891 children (67.87 percent) received bivalent oral polio vaccines while a total of 3,600,773 children have received vitamin A supplementation. Ellison 1932 first documented the protective effect of vitamin A on measles mortality. Egger RJ, Schrijver J, It would have been useful to have the baseline incidence of measles in the study populations reported and if there were epidemics during the study period. The baseline prevalence of vitamin A deficiency and other baseline characteristics vary across countries and even within the same country, as in South Africa. Measles is by no means limited to lowincome countries. They looked at ambulatory participants who were followed up closely for one month with daily and weekly visits to urban health centres. The severity of measles would be less in already vaccinated children (showing vaccine failure) and in areas where the immunization coverage was high. The World Health Organization recommends large oral doses of vitamin A for children living in areas with a high prevalence of vitamin A deficiency to prevent morbidity and mortality, including from measles . West CE, Because low serum levels of vitamin A are associated with severe disease due to measles, vitamin A treatment is recommended for all children with measles. Parenteral and oral formulations of vitamin A are available in the United States. Chowdhury S, Dossetor J, Ross DA, Where loss to follow up was greater than 20%, or where trial authors had excluded participants at a level greater than 15% and for reasons that were deemed to impact on outcomes, that study was excluded. The site is secure. The reduction in deaths from respiratory diseases was seen only in the measles studies. However, data were collected and no side effects were reported in any of the studies. It may also be worth mentioning that the objectives of those reviews were different from the objective of this review. In Coutsoudis' study (Coutsoudis 1991) the supplemented group had significantly higher concentrations than the placebo group, which indicates that the liver stores were not depleted but that there was temporary impairment of mobilization and increased utilization of vitamin A. Houston RM, Only Barclay and Ogaro (Barclay 1987; Ogaro 1993) reported on the development of diarrhea. Bloem MW, However, two doses of vitamin A (200,000 international units (IUs) on consecutive days) reduced the mortality in children aged less than two years (RR 0.21; 95% CI 0.07 to 0.66) and pneumoniaspecific mortality (RR 0.57; 95% CI 0.24 to 1.37). Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. Whittle HC, Peterson DE, Coovadia HM, Coutsoudis A, We used the scores from this assessment in a sensitivity analysis (that is, including and excluding studies of low quality to determine how robust the summary effect measures were). We wish to thank Rennie D'Souza and Ron D'Souza, the previous review authors. The tradeoff of using highdose, oilbased vitamin A versus a waterbased formula has to be viewed in terms of the advantages of each product. #9. When the studies that used the twodose regimen were stratified by formulation (whether water or oilbased) an 81% reduction in the risk of mortality (RR 0.23; 95% CI 0.06 to 0.89) was seen in studies that used waterbased preparations. Summary: A recent study suggests higher doses of Vitamin D3 supplementation during early childhood may reduce the risk of internalizing psychiatric symptoms in later years. Only Barclay's study slightly deviates from the other two studies as he used an oilbased preparation rather than a waterbased formulation. However, these symptoms are minor and transitory, with no known longterm effects and requiring no special treatment (WHO 1998). 1.5 Age more than two years (> 200,000 IU), 4.2 Recovery from diarrhea in < five days, 4.5 Compete clinical recovery in < eight days, 4.12 Recovery from pneumonia in < eight days, Randomized clinical trial using a random number table, 200,000 IU vitamin A orally for 2 days, or routine treatment without vitamin A, Random sequence generation (selection bias), Randomized clinical trial using a random numbers table, Blinding (performance bias and detection bias), Randomized, placebocontrolled, doubleblind trial, 60 children aged 4 to 24 months hospitalized with complicated measles, WHO recommended dose (54.5 mg < 12 months or 109 mg > 12 months) of retinyl palmitate drops or a placebo syrup, The patients were allocated to treatment or placebo groups according to a random numbers table, Vitamin A or placebo was administered by the same person, Blinding of participants and personnel (performance bias), Blinding of outcome assessment (detection bias), 946 children aged 6 to 90 months, in the community, 100,000 IU of vitamin A for children aged 6 to 11 months or 200,000 IU of vitamin A for older children every 4 months for 2 years, The study area was divided into 185 small geographic units, each comprising 30 to 77 compounds. To avoid unitofanalysis errors in clusterrandomized trials, we conducted the analysis at the same level as the allocation, using a summary measurement from each cluster. Barclay 1987 drew attention to the importance of vitamin A therapy in reducing measles mortality and led to the 1987 joint recommendation between the World Health Organization (WHO) and the United Nations International Children's Fund (UNICEF) for the administration of a single oral dose of vitamin A (200,000 international units (IUs), or 100,000 IUs in infants) at the time of initial measles diagnosis in nonxerophthalmic children who lived in areas where measles casefatality rates were greater than 1% (WHO 1988). A similar but apparently stronger reduction effect (66%) was seen in children hospitalized with measles, although this was not significantly different from the 30% seen in lowincome country community settings. Although all the studies reported the baseline nutritional status of the vitamin Asupplemented and placebo groups only, Barclay specified the nutritional status of the children who died; vitamin A recipients suffered lower mortality at every nutritional level. Reddy V. Effect of massive dose vitamin A on morbidity and mortality in Indian children. Vitamin A deficiency. Permeisih D, The twodose, oilbased vitamin A was associated with a statistically significant reduction in risk of mortality in the study by Barclay while the waterbased preparations almost reached statistical significance (RR 0.23; 95% CI 0.06 to 0.89). They were of different durations, in slightly different age groups, using different doses of vitamin A in different formulations (oil or waterbased), in different settings (hospital or community) and in different geographical areas with varying measles casefatality rates. Tarwotjo I, et al. The recommended dose for children 6-11 months is 100 000 International Units (IU), and for children 12-59 months, it is 200 000 IU. The incidence for five trials that excluded highrisk participants was 9.8% and the incidence for the two trials that recruited highrisk participants (with at least one risk factor) was 10.7%. The Cochrane Collaboration. Underwood BA, Keywords used were measles, vitamin A, randomized, controlled trial, respiratory disease, pneumonia, random allocation and clinical trial. London children can get protected through primary schools and community venues. This content does not have an English version. MeSH terms Humans Infant Male Measles / drug therapy* Pseudotumor Cerebri / chemically induced* Vitamin A / administration & dosage Vitamin A / adverse effects* Vitamin A / therapeutic use* Vitamin A Deficiency / drug therapy* Substances The effect of vitamin A was more pronounced in children under the age of two years as a greater reduction in the risk of mortality was observed in this age group. Muherdiyantiningsih BS, Katayose M, Secondly, not all settings, even in Africa, have high measles casefatality rates and the usefulness of vitamin A supplementation where mortality and severe complications are much less frequent, has had limited study" (Ogaro 1993). 87-100%] of children that failed to seroconvert to first dose measles vaccine developed immunity after a second dose. Measles is a viral disease that infects and damages these tissues (Morley 1969a). Duration of pneumonia was reported in only two studies (Coutsoudis 1991; Hussey 1990). Minder C. Bias in metaanalysis detected by a simple, graphical test. The fatality rate in hospitalized children often exceeds 10% (Morley 1969a) and casefatality ratios of up to 20% have been found in community studies in West Africa (Aaby 1984). Only the studies by Rosales and Dollimore were carried out in a community setting, in a group of participants with mild disease (i.e. The most recent Cochrane review for vitamin A treatment of children with measles erroneously includes a supplementation trial; . Beaton GH, Three trials recruited highrisk participants defined as those living in areas with casefatality > 10% or aged two years or less. Hospitalization may be a measure of severity of illness. Joanne Katz, Sc.D. Not every study collected information on recovery from morbidity. #7 AND #10 611 28 Feb 2011 Recent studies show that vitamin A levels decrease during measles and that vitamin A therapy can improve measles outcome in children in the developing world. This suggests that basic health care then was not dissimilar to that available in Africa in the 1980s and 1990s. There were no trials comparing mortality reductions in children with measles who were given a single dose compared to two doses of vitamin A. Susanto D. Increased mortality in children with mild vitamin A deficiency, Increased risk of respiratory disease and diarrhea in children with preexisting mild vitamin A deficiency. Children under the age of 15 years with measles. Treatment of measles cases with vitamin A also has relevance to highincome countries as a reduction is seen in morbidity outcomes in Kawasaki's study. Hussaini G, Although Ellison 1932 was a large study (600 children) we awarded it a low quality score because it was not randomized. No new trials were included or excluded. Another possible explanation is that vitamin A is not mobilized fast enough, even in the presence of adequate hepatic stores (Hussey 1990). Careers, Unable to load your collection due to an error. Orinda VA, The children in the Rosales (Rosales 1996) and Ogaro (Ogaro 1993) studies may not have benefited from receiving vitamin A oilbased preparations in a single dose (200,000 IU) as this might not have been sufficient to reverse the hyporetinemia occurring during measles; the dose may have been stored, mostly in the liver. This raises an issue about whether randomization balanced this important confounder. One explanation is through depletion of hepatic stores. Measles is a major cause of death in children in low-income countries and is particularly dangerous in children with vitamin A deficiency. For the purposes of this review, the outcomes were taken at the time of discharge, hence it is not possible to make comparisons for delayed mortality across these studies. Effect of Vitamin A supplementation on childhood morbidity and mortality, Overcrowding and intensive exposure as determinants of measles mortality. Duggan MB, In settings where vitamin A deficiency is a public health problem, the World Health Organization (WHO) recommends a high-dose vitamin A supplement every six months for children 6-59 months to reduce child morbidity and mortality. Martorell R, Measles Tools and Resources For additional information and resources about measles, visit www.nfid.org/measles and view the following resources: 4 exp PNEUMONIA/ New citation required but conclusions have not changed. In a 100% susceptible population, a single case of measles results in 12 to 18 secondary cases, on average. But when measles does occur, vitamin A can be an effective treatment when appropriately administered by a healthcare professional. Huff DL, Hussey (Hussey 1990) demonstrated that the duration of hospital stay for children given vitamin A was decreased by an average of 4.7 days; by half a day in another study (Kawasaki 1999). The only study carried out in a highincome country (Japan) used onefourth of the recommended dose (100,000 IU), showed a reduced morbidity and did not report any toxicity. Four of the eight studies reported the age distribution of the participants and the ages of those who died. It is assumed that all have been followed up until they were discharged from hospital. government site. As a library, NLM provides access to scientific literature. Journal of experimental & clinical cancer research, 40(1), 1-44. The argument for including this study as part of the sensitivity analysis is that the mortality rates of 8.66 and 3.66 in the placebo and vitamin A groups, respectively, were less than those observed in studies conducted almost 60 years later in Africa. Applies to the following strengths: 10000 intl units; 25000 units; 50000 units/mL; 50000 units; 8000 units Usual Adult Dose for: Vitamin A Deficiency Vitamin/Mineral Supplementation Usual Pediatric Dose for: Vitamin A Deficiency The study by Markowitz et al (Markowitz 1989) highlighted the fact that children aged less than two years of age with low vitamin A levels had a higher risk of dying than those with higher levels; the number of children in the age group older than two years were too few to detect any statistically significant difference. As part of a sensitivity analysis, when we included the study with a poor methodological quality score (Ellison 1932) vitamin A was associated with a 47% reduction in overall mortality (RR 0.70; 95% CI 0.42 to 1.15). Coovadia HM, This study was not randomized and two separate wards were allocated to receive the placebo or vitamin A supplementation. The Coutsoudis study had only one death but dropping this study did not change the summary estimate.

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