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      Effects of lipid-based nutrient supplements and infant and young child feeding counseling with or without improved water, sanitation, and hygiene (WASH) on anemia and micronutrient status: results from 2 cluster-randomized trials in Kenya and Bangladesh

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          ABSTRACT

          Background

          Anemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene.

          Objective

          We evaluated the effects of water quality, sanitation, handwashing, and nutrition interventions on micronutrient status and anemia among children in rural Kenya and Bangladesh.

          Design

          We nested substudies within 2 cluster-randomized controlled trials enrolling pregnant women and following their children for 2 y. These substudies included 4 groups: water, sanitation, and handwashing (WSH); nutrition (N), including lipid-based nutrient supplements (LNSs; ages 6–24 mo) and infant and young child feeding (IYCF) counseling; WSH+N; and control. Hemoglobin and micronutrient biomarkers were measured after 2 y of intervention and compared between groups using generalized linear models with robust SEs.

          Results

          In Kenya, 699 children were assessed at a mean ± SD age of 22.1 ± 1.8 mo, and in Bangladesh 1470 participants were measured at a mean ± SD age of 28.0 ± 1.9 mo. The control group anemia prevalences were 48.8% in Kenya and 17.4% in Bangladesh. There was a lower prevalence of anemia in the 2 N intervention groups in both Kenya [N: 36.2%; prevalence ratio (PR): 0.74; 95% CI: 0.58, 0.94; WSH+N: 27.3%; PR: 0.56; 95% CI: 0.42, 0.75] and Bangladesh (N: 8.7%; PR: 0.50; 95% CI: 0.32, 0.78; WSH+N: 7.9%, PR: 0.46; 95% CI: 0.29, 0.73). In both trials, the 2 N groups also had significantly lower prevalences of iron deficiency, iron deficiency anemia, and low vitamin B-12 and, in Kenya, a lower prevalence of folate and vitamin A deficiencies. In Bangladesh, the WSH group had a lower prevalence of anemia (12.8%; PR: 0.74; 95% CI: 0.54, 1.00) than the control group, whereas in Kenya, the WSH+N group had a lower prevalence of anemia than did the N group (PR: 0.75; 95% CI: 0.53, 1.07), but this was not significant ( P = 0.102).

          Conclusions

          IYCF counseling with LNSs reduced the risks of anemia, iron deficiency, and low vitamin B-12. Effects on folate and vitamin A varied between studies. Improvements in WSH also reduced the risk of anemia in Bangladesh but did not provide added benefit over the nutrition-specific intervention.

          These trials were registered at clinicaltrials.gov as NCT01590095 (Bangladesh) and NCT01704105 (Kenya).

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          Most cited references32

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          A structural approach to selection bias.

          The term "selection bias" encompasses various biases in epidemiology. We describe examples of selection bias in case-control studies (eg, inappropriate selection of controls) and cohort studies (eg, informative censoring). We argue that the causal structure underlying the bias in each example is essentially the same: conditioning on a common effect of 2 variables, one of which is either exposure or a cause of exposure and the other is either the outcome or a cause of the outcome. This structure is shared by other biases (eg, adjustment for variables affected by prior exposure). A structural classification of bias distinguishes between biases resulting from conditioning on common effects ("selection bias") and those resulting from the existence of common causes of exposure and outcome ("confounding"). This classification also leads to a unified approach to adjust for selection bias.
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            Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis.

            The World Health Organization recommends serum ferritin concentrations as the best indicator of iron deficiency (ID). Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated. The objective was to estimate the increase in ferritin in 32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP), individually and in combination, and to calculate factors to remove the influence of inflammation from ferritin concentrations. We estimated the increase in ferritin associated with inflammation (ie, CRP gt 5 mg/L and/or AGP gt 1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies), and women (16 studies) (n = 8796 subjects). In 2-group analyses (either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups: reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only). In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P lt 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P lt 0.001) higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ap 30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID. Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups.
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              Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique.

              The measurement of vitamin A (VA) and iron status is very important in the assessment of nutritional deficiencies. The objective of this research was to develop a sandwich ELISA technique for the simultaneous measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein (CRP) as indicators for VA and iron status. The inclusion of CRP as marker of infection allows for more accurate interpretation of VA and iron status. This is accomplished in a 30-microL serum or plasma sample using an ELISA with different capture and detection antibodies and different dilutions of the sample. Commercially available clinical serum controls were used for calibration purposes. The developed assays were compared to commercially available traditional tests. Regression coefficients comparing both assays were better than 0.84 (P < 0.001). Using a limited sample set, the sandwich ELISA assay produced very similar specificity and sensitivity compared to traditional methods when common cutoff values were applied. Intra- and interassay variability was between 5 and 14% for all tests. The cost of the materials for all 5 measurements decreases to less than $1/sample if a large number of samples is analyzed. Due to the low cost, high throughput, and comparability to traditional tests, this procedure has several advantages for assessing VA and iron status in population surveys.
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                Author and article information

                Journal
                Am J Clin Nutr
                Am. J. Clin. Nutr
                ajcn
                The American Journal of Clinical Nutrition
                Oxford University Press
                0002-9165
                1938-3207
                January 2019
                09 January 2019
                09 January 2019
                : 109
                : 1
                : 148-164
                Affiliations
                [1 ]Department of Nutrition, University of California, Davis, Davis, CA
                [2 ]Division of Epidemiology and Biostatistics, University of California, Berkeley, Berkeley, CA
                [3 ]Department of Civil and Environmental Engineering
                [4 ]Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA
                [5 ]International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh
                [6 ]Innovations for Poverty Action, Nairobi, Kenya
                [7 ]USDA, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA
                Author notes
                Address correspondence to CPS (e-mail: cpstewart@ 123456ucdavis.edu ).

                Present address for MK: One Acre Fund, Nairobi, Kenya.

                Present address for GR: Waterborne Disease Prevention Branch, Division of Foodborne, Waterborne, and Environmental Diseases, CDC, 1600 Clifton Road, Atlanta, GA 30329.

                Present address for CN: Mathmatica Policy Research, 1100 First Street, NE, 12th Floor, Washington, DC 20002.

                Present address for AJP: Department of Civil and Environmental Engineering, Tufts University, 200 College Avenue, Medford, MA 02155.

                Author information
                http://orcid.org/0000-0003-4575-8571
                http://orcid.org/0000-0002-4185-3451
                http://orcid.org/0000-0002-3877-3469
                http://orcid.org/0000-0001-6193-2221
                http://orcid.org/0000-0003-4528-752X
                http://orcid.org/0000-0002-5032-5327
                http://orcid.org/0000-0003-3883-1208
                http://orcid.org/0000-0001-6510-3172
                http://orcid.org/0000-0001-6105-7295
                http://orcid.org/0000-0002-5058-4935
                http://orcid.org/0000-0001-6002-1514
                http://orcid.org/0000-0002-1347-4446
                http://orcid.org/0000-0003-0520-2683
                http://orcid.org/0000-0001-5385-899X
                Article
                nqy239
                10.1093/ajcn/nqy239
                6358037
                30624600
                f069a068-1a06-4422-be59-47dcd12eba50
                © 2018 American Society for Nutrition.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 May 2018
                : 28 February 2018
                : 14 August 2018
                Page count
                Pages: 17
                Categories
                Original Research Communications

                Nutrition & Dietetics
                lipid-based nutrient supplement,water,sanitation,hygiene,anemia,micronutrients,children

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