Fig 3 - uploaded by Filippo Curtale
Content may be subject to copyright.
Comparison of the 5-year costs of the capsule distribution and nutrition education components of the project, by number of districts covered.
Source publication
The impact on vitamin A deficiency (VAD), wasting malnutrition, and excessive childhood mortality of two alternative approaches-nutrition education and mega-dose capsule distribution (6-12-month-olds: 100,000 IU; 1-5-year-olds: 200,000 IU)-in communities in Nepal are compared. Approximately 40,000 children from 75 locations in seven districts in tw...
Context in source publication
Context 1
... that influ- ence community risk (rather than individual risk) are maternal literacy and agricultural practices. The nu- trition education programme can also affect cultiva- tion practices and patterns, and the maternal literacy programme directly reduces one of the risk factors that predict xerophthalmia, wasting, or mortality risk in a village. Fig. 3 shows that economies of scales can be generated in the nutrition education programme as it is enlarged to a national programme. For a nutrition programme, savings can be made by spreading the investment cost of materials development and the start-up cost over a larger group of people. As the nutrition education programme reached higher ...
Citations
... Types of studies. Of the included studies, five trials [23][24][25][26][27] were individual-RCT designs and the remaining ten trials [28][29][30][31][32][33][34][35][36][37] were cluster-RCT. Further information about individual studies is available in "S3 Appendix". ...
... Location/Setting. Studies took place in 6 countries; five trials in India [26,28,32,35,36], three trials in Nepal [29,31,37], one trial in Indonesia [34], two trials in Ghana [25,33], two trials in Guinea-Bissau [23,24] and one trial each in Sudan [30] and Congo [27]. ...
... Comparisons. Five trials compared VAS against usual care [27,29,31,34,35] and the remainder of the ten trials used a placebo as a comparator. ...
Background
The World Health Organization has recommended Vitamin A supplementation for children in low- and middle-income countries for many years to reduce child mortality. Nepal still practices routine Vitamin A supplementation. We examined the potential current impact of these programs using national data in Nepal combined with an update of the mortality effect estimate from a meta-analysis of randomized controlled trials.
Methods
We used the 2017 Cochrane review as a template for an updated meta-analysis. We conducted fresh searches, re-applied the inclusion criteria, re-extracted the data for mortality and constructed a summary of findings table using GRADE. We applied the best estimate of the effect obtained from the trials to the national statistics of the country to estimate the impact of supplementation on under-five mortality in Nepal.
Results
The effect estimates from well-concealed trials gave a 9% reduction in mortality (Risk Ratio: 0.91, 95% CI 0.85 to 0.97, 6 trials; 1,046,829 participants; low certainty evidence). The funnel plot suggested publication bias, and a meta-analysis of trials published since 2000 gave a smaller effect estimate (Risk Ratio: 0.96, 95% CI 0.89 to 1.03, 2 trials, 1,007,587 participants), with the DEVTA trial contributing 55.1 per cent to this estimate. Applying the estimate from well-concealed trials to Nepal’s under-five mortality rate, there may be a reduction in mortality, and this is small from 28 to 25 per 1000 live births; 3 fewer deaths (95% CI 1 to 4 fewer) for every 1000 children supplemented.
Conclusions
Vitamin A supplementation may only result in a quantitatively unimportant reduction in child mortality. Stopping blanket supplementation seems reasonable given these data.
... This is quite understandable since educational programs can be quite challenging and costly. A cost analysis of the national vitamin A supplementation programs in Nepal comparing the cost of capsule distribution with education indicates that, although the effects of both programs were similar, the capsule program achieved higher coverage rates at a lower cost while the educational intervention provided economies of scale and potential for long-term sustainability [18]. ...
The aim was to evaluate the vitamin A supplementation in three districts of Ghana. The specific objectives were to determine the proportion of children aged 6 to 59 months who received vitamin A supplements in the 12 months before 2010, to determine if the actual coverage corresponds with data from the Ministry of health of Ghana and to determine the factors associated with non-uptake of vitamin A supplements.
Methods: All the districts in the Ashanti region were stratified by ecological zone. Simple random sampling was used to select one district in each of the zones. Each selected district was divided into sub districts and probability proportional to size was then used to select villages where the clusters would be located. The caretakers of children were interviewed to get data on demographics, socioeconomics, receiving vitamin A supplements and knowledge of vitamin A. Coverage was assessed from mother’s own account and a direct inspection of the health charts of the children.
Results: Comparing mother’s account of coverage with health records showed that records of supplementation coverage were lower than coverage reported by the mothers. Seventy nine percent of mothers reported receiving one dose in the last year whilst the health charts showed 63.5%. Forty percent of the mothers reported receiving two doses in the last year against 20.1% recorded on the health charts. In a multivariate logistic regression analysis, the factors associated with poor uptake of vitamin A supplements were, type of material house was made of, caretakers’ ability to correctly identify vitamin A supplements, knowledge of the medical effects of vitamin A deficiency and how the child got the vitamin A supplements.
Conclusion: This study shows satisfactory coverage if coverage is taken as receiving at least one dose in the last year but poor coverage if the recommended two doses is used. Poor knowledge of the medical effect of vitamin A deficiency and natural sources of vitamin A did not affect coverage. There is the need to improve on documentation and to redefine coverage.
... As presented in a recent review [7], this conclusion is substantiated when more recent studies are included ( Figure 1). [2], the two subsequent [8,9], and the two new trials [10,11] of vitamin A supplementation to children above 6 months of age (Modified by Beaton et al., 1993 [2], and first presented in Benn et al., Int. J. Epidemiol. ...
... VAS has been seen as a golden bullet against child mortality, and enormous resources, both in terms of dollars and opportunity costs, have been invested in providing VAS biannually to millions of children every year. As an unfortunate side-effect, VAS programs may have prevented the [2], the two subsequent [8,9], and the two new trials [10,11] of vitamin A supplementation to children above 6 months of age (Modified by Beaton et al., 1993 [2], and first presented in Benn et al., Int. J. Epidemiol. ...
It is usually acknowledged that high-dose vitamin A supplementation (VAS) provides no sustained improvement in vitamin A status, and that the effect of VAS on mortality is more likely linked to its immunomodulating effects. Nonetheless, it is widely assumed that we can deduce something about the need for continuing or stopping VAS programs based on studies of the biochemical prevalence of vitamin A deficiency (VAD). This is no longer a tenable assumption. The justification for using VAS is to reduce child mortality, but there is now doubt that VAS has any effect on overall child mortality. What we need now are not surveys of VAD, but proper randomized trials to evaluate whether VAS has beneficial effects on overall child survival.
... In sum, these trials included 1 180 718 children, average age 31.5 months (range: 6-63 months) at baseline (Table 1). 1,7,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In 9 of the 17 trials, a factorial randomized design was used, with vitamin E as a second intervention. Supplementation frequency ranged from every 3 months to every 2 years, total cumulative dose 134 361 to 2 200 000 IU (mean ¼ 667 132 IU; standard deviation [SD]: 540 795), and duration of supplementation 4 to 60 months (mean ¼ 15.4; SD: 12.8). ...
Background:
Although vitamin A supplementation reduces child mortality, it remains unclear whether dosing frequency, total dose, or duration modifies effectiveness.
Objective:
Determine whether mortality effects of vitamin A vary by dosing frequency, total dose, or duration.
Methods:
Meta-analysis of randomized controlled trials, identified by systematic review and expert opinion, utilizing relatively standard World Health Organization doses in children <5 years. Meta-regression evaluated whether mortality effects varied by dosing frequency, total dose, or supplementation duration.
Results:
Identified 17 trials, including 1,180,718 children, mean (standard deviation [SD]) age 31.5 (15.4) months at baseline. Supplementation frequency ranged every 3 months-every 2 years, supplementation duration 4-60 months (mean = 15.4; SD = 12.8), and total dose 134,361-2,200,000 IU (mean = 667,132 IU; SD = 540,795). Compared with control, vitamin A reduced mortality 22% (95% confidence interval [CI] = 10-32; P = 0.002). This protective effect was not modified by increasing supplementation frequency (dose/year: relative risk [RR] = 1.02; 95% CI = 0.98-1.06; P = .22), total dose (per 200,000 IU: RR = 1.02; 95% CI = 0.97-1.06; P = .31), nor supplementation duration (per year: RR = 1.06; 95% CI = 0.97-1.15; P = 0.14). Multivariate meta-regression showed similar results. Sensitivity analyses excluding 1 controversial trial (Aswathi 2013) did not alter findings.
Conclusion:
Results confirm benefits of vitamin A supplementation in children <5 years in nations with vitamin A deficiency, without influence of frequency, total dose, or dosing duration within ranges evaluated. These findings inform design and efficiency of vitamin A supplementation policies.
... Most of the studies (n = 18) were intervention studies (pre and post or two group comparison), ten RCT, one randomised crossover study and one crossover trial. The sample sizes of the studies ranged from 42 [36] to 40,000 [37] participants. The duration of the study also varied; from a once-off nutrition counselling training [38] to a 48 months nutrition education intervention in Nicaragua [39]. ...
Background
Although linkages have been found between agricultural interventions and nutritional health, and the development of clean fuels and improved solid fuel stoves in reducing household air pollution and adverse health effects, the extent of the potential of combined household interventions to improve health, nutrition and the environment has not been investigated. A systematic review was conducted to identify the extent and type of community-based agricultural and household interventions aimed at improving food security, health and the household environment in low and middle income countries. MethodsA systematic search of Ovid MEDLINE, PUBMED, EMBASE and SCOPUS databases was performed. Key search words were generated reflecting the “participants, interventions, comparators, outcomes and study design” approach and a comprehensive search strategy was developed following “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” recommendations. Any community-based agricultural and/or household interventions were eligible for inclusion if the focus was to improve at least one of the outcome measures of interest. All relevant study designs employing any of these interventions (alone/in combination) were included if conducted in Low and middle income countries. Review articles, and clinical and occupational studies were excluded. ResultsA total of 123 studies were included and grouped into four intervention domains; agricultural (n = 27), air quality (n = 34), water quality (n = 32), and nutritional (n = 30). Most studies were conducted in Asia (39.2 %) or Africa (34.6 %) with the remaining 26.1 % in Latin America. Very few studies (n = 11) combined interventions across more than one domain. The majority of agricultural and nutritional studies were conducted in Africa and Asia, whereas the majority of interventions to improve household air quality were conducted in Latin America. Conclusions
It is clear that very little trans-disciplinary research has been done with the majority of studies still being discipline specific. It also appears that certain low and middle income countries seem to focus on domain-specific interventions. The review emphasizes the need to develop holistic, cross-domain intervention packages. Further investigation of the data is being conducted to determine the effectiveness of these interventions and whether interdisciplinary interventions provide greater benefit than those that address single health or community problems.
... It is evident that Vitamin A prevents deaths due to Measles but the correct intervention would be to give Measles immunization not to give a mega dose of Vitamin A. Kapil et al. suggested that it is the occasion to discontinue giving indiscriminate enormous doses of synthetic vitamin A to Indian children, which has to be considered equivalent to Nepal as a neighbouring country with ethnic similarities [18]. Pant et al. conducted a three-year follow-up evaluation of the effectiveness of two approaches to Vitamin A deficiency prevention--nutrition education and megadose capsule distribution--with almost 40,000 children 6 months to 10 years of age in Nepal [19]. Although the effects of both programmes were equal the capsule achieved higher coverage rates at a lower expenditure while the educational intervention provided economies of scale and potential for long-term sustainability. ...
... Although the effects of both programmes were equal the capsule achieved higher coverage rates at a lower expenditure while the educational intervention provided economies of scale and potential for long-term sustainability. The most practical approach would be a comprehensive national programme that included both these components as well as maternal literacy training by their study [19]. There are several systematic reviews, randomized control trials, cohort studies and commentaries published in this context but still there is no precautionary measures have been taken. ...
Journal of Biomedical Sciences 2015, 2(4):28-30
... The analysis did not take into account the possible changes in epidemiological patterns in the time between the studies; moreover since the weight ascribed to the newer studies was only 11%, it is not surprising that the conclusion was not altered. What is surprising is that it was not stressed that from 1994 on, only one study 22 showed a mortality effect compared with the no-intervention comparison group [P < 0.01, relative risk (RR) ¼ 0.57, 95% CI ¼ 0.42-0.77), although not compared with nutrition education. ...
... In this light, the DEVTA result is less surprising, as we have noted elsewhere. 23 The change through time is illustrated in Figure 2. 6,14,19,22,[24][25][26][27][28][29][30][31][32] Here, the results of trials quoted in the Imdad et al. (2011) 19 meta-analysis are plotted against year of research completion, in terms of the estimated protective effect [1-relative risk, i.e. equivalent to the 23% reduction in mortality widely quoted from Beaton et al. (1993)]. 15 (Three trials of low weight in the Imdad metaanalysis, omitted also in the DEVTA 6 meta-analysis, are excluded-see notes to Figure 2-which has little effect on the results). ...
The prevalence of vitamin A (VA) deficiency, which affects about one-third of children in developing countries, is falling only slowly. This is despite extensive distribution and administration of periodic (4– to 6-monthly) high-dose VA capsules over the past 20 years, now covering a reported 80% of children in developing countries. This massive programme was motivated largely by an expectation of reducing child mortality, stemming from findings in the 1980s and early 90s. Efficacy trials since 1994 have in most cases not confirmed a mortality impact of VA capsules. Only one large scale programme evaluation has ever been published, which showed no impact on 1–6–year-old mortality (the DEVTA trial, ending in 2003, in Uttar Pradesh, India). Periodic high-dose VA capsules may have less relevance now with changing disease patterns (notably, reductions in measles and diarrhoea). High-dose VA 6-monthly does not reduce prevalence of the deficiency itself, estimated by low serum retinol. It is proposed that: (i) there is no longer any evidence that intermittent high-dose VA programmes are having any substantial mortality effect, perhaps due to changing disease patterns; (ii) frequent intakes of vitamin A in physiological doses —e.g. through food-based approaches, including fortification, and through regular low-dose supplementation—are highly effective in increasing serum ret-inol (SR) and reducing vitamin A deficiency; (iii) therefore a policy shift is needed, based on consideration of current evidence. A prudent phase-over is needed towards increasing frequent regular intakes of VA at physiological levels, daily or weekly, replacing the high-dose periodic capsule distribution programmes. Moving resources in this direction must happen sooner or later: it should be sooner.
... Season is a potential effect modifier of VAS, which may be linked to pathogen exposure and could provide clues about the biological mechanisms behind the variable effect of VAS was again no strong association between the effect of VAS and degree of underlying VAD. 17,18 In the two new RCTs in children above 6 months of age, the Indian RCT was conducted in a population with 3.5% of control children having Bitot's spots, a clinical manifestation of xerophthalmia. 15 The Guinea-Bissau RCT was conducted in a population with no xerophthalmia but more than 60% of the children having low levels of serum retinol-binding protein. ...
... The relative risk comparing vitamin A vs no vitamin A by prevalence of xerophthalmia in the original eight, the two subsequent, and the two new trials of vitamin A supplementation to children above 6 months of age2,14,15,17,18 (modified from Beaton et al.2 ). ...
Vitamin A deficiency (VAD) is associated with increased mortality. To prevent VAD, WHO recommends high-dose vitamin A supplementation (VAS) every 4-6 months for children aged between 6 months and 5 years of age in countries at risk of VAD. The policy is based on randomized clinical trials (RCTs) conducted in the late 1980s and early 1990s. Recent RCTs indicate that the policy may have ceased to be beneficial. In addition, RCTs attempting to extend the benefits to younger children have yielded conflicting results. Stratified analyses suggest that whereas some subgroups benefit more than expected from VAS, other subgroups may experience negative effects.
We reviewed the potential modifiers of the effect of VAS. The variable effect of VAS was not explained by underlying differences in VAD. Rather, the effect may depend on the sex of the child, the vaccine status and previous supplementation with vitamin A. Vitamin A is known to affect the Th1/Th2 balance and, in addition, recent evidence suggests that vitamin A may also induce epigenetic changes leading to down-regulation of the innate immune response. Thus VAS protects against VAD but has also important and long-lasting immunological effects, and the effect of providing VAS may vary depending on the state of the immune system.
To design optimal VAS programmes which target those who benefit and avoid those harmed, more studies are needed. Work is ongoing to define whether neonatal VAS should be considered in subgroups. In the most recent RCT in older children, VAS doubled the mortality for males but halved mortality for females. Hence, we urgently need to re-assess the effect of VAS on older children in large-scale RCTs powered to study effect modification by sex and other potential effect modifiers, and with nested immunological studies.
© The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association.
... The analysis did not take into account the possible changes in epidemiological patterns in the time between the studies; moreover since the weight ascribed to the newer studies was only 11%, it is not surprising that the conclusion was not altered. What is surprising is that it was not stressed that from 1994 on, only one study 22 showed a mortality effect compared with the no-intervention comparison group [P < 0.01, relative risk (RR) ¼ 0.57, 95% CI ¼ 0.42-0.77), although not compared with nutrition education. ...
... .6,14,19,22,[24][25][26][27][28][29][30][31][32] Here, the results of trials quoted in theImdad et al. (2011) 19 meta-analysis are plotted against year of research completion, in terms of the estimated protective effect [1-relative risk, i.e. equivalent to the 23% reduction in mortality widely quoted fromBeaton et al. (1993)].15 (Three trials of low weight in the Imdad metaanalysis, omitted also in the DEVTA 6 meta-analysis, are excluded-see notes toFigure 2-which has little effect on the results). ...
The prevalence of vitamin A (VA) deficiency, which affects about one-third of children in developing countries, is falling only slowly. This is despite extensive distribution and administration of periodic (4- to 6-monthly) high-dose VA capsules over the past 20 years, now covering a reported 80% of children in developing countries. This massive programme was motivated largely by an expectation of reducing child mortality, stemming from findings in the 1980s and early 90s. Efficacy trials since 1994 have in most cases not confirmed a mortality impact of VA capsules. Only one large scale programme evaluation has ever been published, which showed no impact on 1-6-year-old mortality (the DEVTA trial, ending in 2003, in Uttar Pradesh, India). Periodic high-dose VA capsules may have less relevance now with changing disease patterns (notably, reductions in measles and diarrhoea). High-dose VA 6-monthly does not reduce prevalence of the deficiency itself, estimated by low serum retinol. It is proposed that: (i) there is no longer any evidence that intermittent high-dose VA programmes are having any substantial mortality effect, perhaps due to changing disease patterns; (ii) frequent intakes of vitamin A in physiological doses -e.g. through food-based approaches, including fortification, and through regular low-dose supplementation-are highly effective in increasing serum retinol (SR) and reducing vitamin A deficiency; (iii) therefore a policy shift is needed, based on consideration of current evidence. A prudent phase-over is needed towards increasing frequent regular intakes of VA at physiological levels, daily or weekly, replacing the high-dose periodic capsule distribution programmes. Moving resources in this direction must happen sooner or later: it should be sooner.
... Imdad et al. conducted a meta-analysis to evaluate the effects of vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age (211) (4,37,48,94,124,130,133,192,262,346,435,471,481,495) reported all-cause mortality. Vitamin A supplementation was associated with a 24% reduction in all-cause mortality (RR = 0.76, 95% CI: 0.69, 0.83). ...
... Studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation were also excluded. Forty-three trials (N = 215,633) met inclusion criteria; 39 studies were included in the final meta-analysis (4,27,34,37,48,57,90,94,124,130,133,155,192,223,259,260,262,270,271,346,363,364,372,377,380,387,410,414,416,419,429,431,434,435,471,473,481,495). Seventeen trials(N = 194,795) ...
ABSTRACT An evidence-based systematic review of vitamin A by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated and reproducible grading rationale. This paper includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
