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  • There is a lot to celebrate and

    2019-04-29

    There is a lot to celebrate and applaud in this month\'s issue of , but also some sobering findings and a clear demonstration of the need for more research. To start with the positive, Osman Sankoh and fellow INDEPTH Network colleagues announce a new freely accessible repository of Health and Demographic Surveillance System data generated by its member centres across Africa, Asia, and the Pacific. This triumph of dedication, which currently holds data on around 800 000 individuals and more than 3·7 million person-years of observation, represents the first harmonised database of longitudinal population-based data from low-income and middle-income countries. The Network also launched INDEPTHStats, a publicly accessible source of summary statistics generated from the data repository. The INDEPTH team should be congratulated on this effort, which can only improve as more data are added and more centres sign up to the Network.
    In this issue of , Sant-Rayn Pasricha and colleagues report findings from a meta-analysis examining the effects of daily iron supplementation on the health of young children. Eligibility included randomised controlled trials (RCTs) that provided intervention in the form of iron or a placebo to children within the age range of 4–23 months. The authors report on multiple outcomes relevant to programmes aimed at controlling anaemia in developing countries, namely: haematological and iron status, cognitive and psychomotor development, physical growth, safety, and other micronutrients. The haematological effects of iron deficiency and supplementation have long been known, but, more recently, non-haematological findings of iron deficiency have been acknowledged. These non-haematological outcomes are often subtle and, therefore, may be largely underestimated. The strongest reported findings were for the haematology and iron status outcomes, for which increased haematology and iron status were seen in those supplemented with iron. Subgroup analyses were informative and consistent with previous findings that indicated greater increases in these outcomes for those who began the trial with the poorest iron status. Findings of no effect of iron supplementation on cognitive and psychomotor development may seem counterintuitive, given the known necessity of iron for optimal Tenofovir Disoproxil Fumarate processing. One interpretation is that studies need to be longer because differences may not emerge until a later age. However, these findings are consistent with those of previous reports. The large volume of published animal studies detailing the neurological effects of iron deficiency renders it foolish to conclude that iron is not necessary for brain processes in this age group, but these findings are a reminder of the many unanswered questions that we have with respect to this relation. Of concern are the findings of reduced length and weight gain and increased prevalence of fever in those receiving iron. These findings did become non-significant when only studies regarded to be at low risk for bias were included. However, the finding of increased vomiting with iron supplementation was seen even in the one study with low risk of bias. It is possible that children who were iron deficient, anaemic, or both at baseline benefitted from supplementation whereas those who were iron sufficient at baseline experienced harm. Lack of stratification of analyses by baseline iron status makes this impossible to determine. Altered zinc status in those receiving combined iron and zinc supplementation has been reported previously but it should be remembered that zinc status of children supplemented with the combined nutrients is still higher than those who receive a placebo. This paper contributes to the literature in multiple ways. First, the focus on this young age group is informative. Given the incredible rate of growth and the developmental changes occurring in this age group, coupled with the fact that the highest prevalence of iron-deficiency anaemia is found in children younger than 4 years (ranging from 7% in high-income countries to 76% in south Asia), it is imperative that we clearly understand the risks and benefits of iron supplementation in this age group. It is also helpful that Pasricha and colleagues report on multiple outcomes on which policy is likely to be based. Most meta-analyses to date have not been as focused on one particular age group yet broad in the outcomes assessed. The authors\' inclusion criteria (confined to RCTs in otherwise well, community, or outpatient children) helped to focus the analysis and allowed for better comparability across studies. Although this does not guarantee elimination of all potential confounders, it narrows the possibility. The clear assessment of risk of bias provided for each study and the multiple subgroup analyses allowed for better interpretability of the findings and are pieces frequently missing from previous analyses. Limitations of meta-analyses are often based on the strength of the data available. Only 26% of the eligible studies were judged to be at low risk of overall bias in this analysis. Other studies may have been at low risk for bias but failed to report information necessary for this determination. All RCTs have a methodology for randomisation and concealment of allocation and reporting such information will allow for better comparison across studies in the future. It is also imperative that future reports include information on adherence, preferably in a standardised manner. Future meta-analyses would also benefit from findings where data have been stratified by baseline iron status. Iron is an essential trace element required for growth, development, and normal cellular functioning. However, there is also considerable danger of toxicity with iron if excessive amounts accumulate in the body. Although a finely tuned feedback control system helps to limit the possibility of excessive accumulation, it is possible that various pathologies may alter this feedback, placing the individual at risk. Therefore, knowing the baseline iron status of an individual will aid in properly interpreting the research findings. As stated by Pasrich and colleagues, more RCTs of non-haematological outcomes are needed to make definitive conclusions as to the benefits and harm of daily iron supplementation in this age group. Detailed reporting of findings that include stratification of results by baseline iron status will provide us with data needed to properly inform policy.