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1. Perinatal intervention strategies providing food with micronutrients to pregnant and breastfeeding women in low‐ and middle‐income countries: A scoping review

Author

Christine M. McDonald, K. Ryan Wessells, Christine P. Stewart, Kathryn G. Dewey, Saskia dePee, Ritu Rana, Hajra Hafeez‐ur‐Rehman, Martin N. Mwangi, and Sonja Y. Hess

Subjects
antenatal nutrition, balanced energy protein, lactation, LNS, maternal nutrition, perinatal nutrition, Pediatrics, RJ1-570, Gynecology and obstetrics, RG1-991, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract In resource‐constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient‐fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low‐ and middle‐income countries. We conducted a PubMed search using pre‐defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid‐based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk‐based beverages [n = 2], and local food/snacks [n = 3]) that provided 118–750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost‐effectiveness, and incorporation into multi‐component interventions.

Published
2024
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2. Why small-quantity lipid-based nutrient supplements should be integrated into comprehensive strategies to prevent child undernutrition in nutritionally vulnerable populations: response to Gupta et al.’s commentary

Author

Kathryn G Dewey, Christine P. Stewart, Christine McDonald, K. Ryan Wessells, Charles D. Arnold, Elizabeth L. Prado, Souheila Abbeddou, Seth Adu-Afarwuah, Benjamin F. Arnold, Per Ashorn, Ulla Ashorn, Sania Ashraf, Elodie Becquey, Robert E. Black, Kenneth H. Brown, Parul Christian, John M. Colford, Lia C.H. Fernald, Emanuela Galasso, Lotta Hallamaa, Sonja Hess, Jean H. Humphrey, Lieven Huybregts, Lora L. Iannotti, Kaniz Jannat, Elizabeth Y. Jimenez, Anna Lartey, Agnes Le Port, Jef L. Leroy, Stephen P. Luby, Kenneth Maleta, Andrew Matchado, Susana L. Matias, Mduduzi NN Mbuya, Malay K. Mridha, Rina R. Paul, Harriet Okronipa, Jean-Bosco Ouédraogo, Amy J. Pickering, Andrew J. Prendergast, Marie Ruel, Saijuddin Shaikh, Ann M. Weber, and Patricia Wolff

Subjects
prevention of malnutrition, Nutrition. Foods and food supply, TX341-641, Food processing and manufacture, TP368-456
Published
2023
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3. Out-of-pocket costs and time spent attending antenatal care services: a case study of pregnant women in selected rural communities in Zinder, Niger

Author

Césaire T. Ouédraogo, Stephen A. Vosti, K. Ryan Wessells, Charles D. Arnold, M. Thierno Faye, and Sonja Y. Hess

Subjects
Out-of-pocket costs, Antenatal care, Opportunity cost of time, Pregnancy, Niger, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Despite an official policy of exemption from health care costs, pregnant women in Niger still face some out-of-pocket costs (OPC) in addition to time costs when they attend antenatal care (ANC) services. We aimed to: 1) assess the OPC for pregnant woman attending ANC, 2) estimate the time spent to attend ANC and the opportunity cost of that time, and 3) assess how OPC and time spent to attend ANC affected ANC attendance. Methods Data were obtained from a quasi-experimental descriptive study carried out in the region of Zinder, Niger, which compared pre- and post-intervention cohorts of pregnant women (n = 1736 women who reported attending ANC during their current pregnancy). An ANC attendance score was developed to describe the timing of ANC attendance in regard to the WHO recommendation of attending 4 ANC sessions. OPC and time spent were evaluated separately for associations with ANC attendance using Spearman correlations. Results The mean (±SD) age of pregnant women was 25.0 ± 6.4 yr, 19.0% were ≤ 19 yr and 99.7% were in their second or third trimester of gestation at the time of the interview. Among those who were > 13 weeks and > 27 weeks of gestation, 4.0 and 74.4% had attended ANC during their first and second trimesters, respectively. The median (1st quartile (Q1), 3rd quartile (Q3)) ANC score was 0 (− 1, 0), reflecting that the majority of women failed to follow the WHO recommendation. More than half of the women (72.5%) experienced OPC related to ANC. The majority of women (> 80%) reported spending ~ 3 h for an ANC visit, including travel and waiting time. Time spent to attend ANC was not associated with ANC attendance score. Women who experienced OPC, and those who received iron folic acid (IFA) or long-lasting insecticide-treated bednets during an ANC visit, were more likely to have a higher ANC attendance score compared to those who did not. Conclusion OPC and time spent were not identified as barriers to ANC visits, and IFA and long-lasting insecticide-treated bednets distribution could be used to motivate pregnant women to attend ANC. Trial registration The NiMaNu project was registered at www.clinicaltrials.gov as NCT01832688 . Registered 16 April 2013.

Published
2021
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4. A multicenter analytical performance evaluation of a multiplexed immunoarray for the simultaneous measurement of biomarkers of micronutrient deficiency, inflammation and malarial antigenemia

Author

Eleanor Brindle, Lorraine Lillis, Rebecca Barney, Pooja Bansil, Sonja Y. Hess, K. Ryan Wessells, Césaire T. Ouédraogo, Francisco Arredondo, Mikaela K. Barker, Neal E. Craft, Christina Fischer, James L. Graham, Peter J. Havel, Crystal D. Karakochuk, Mindy Zhang, Ei-Xia Mussai, Carine Mapango, Jody M. Randolph, Katherine Wander, Christine M. Pfeiffer, Eileen Murphy, and David S. Boyle

Subjects
Medicine, Science
Abstract

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at

Published
2021

5. Comparison of two forms of daily preventive zinc supplementation versus therapeutic zinc supplementation for diarrhea on young children’s physical growth and risk of infection: study design and rationale for a randomized controlled trial

Author

K. Ryan Wessells, Kenneth H. Brown, Sengchanh Kounnavong, Maxwell A. Barffour, Guy-Marino Hinnouho, Somphou Sayasone, Charles B. Stephensen, Kethmany Ratsavong, Charles P. Larson, Charles D. Arnold, Kimberly B. Harding, Gregory A. Reinhart, Ganjana Lertmemongkolchai, Supan Fucharoen, Robin M. Bernstein, and Sonja Y. Hess

Subjects
Zinc, Diarrhea, Micronutrient, Supplementation, Home-fortification, Growth, Nutrition. Foods and food supply, TX341-641, Food processing and manufacture, TP368-456, Medicine (General), R5-920
Abstract

Abstract Background Zinc is an essential nutrient that is required for children’s normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Daily or weekly preventive zinc supplementation has been shown to improve growth and reduce the risk of infection, while therapeutic zinc supplementation for 10–14 days is recommended for the treatment of diarrhea. The overall objective of the present study is to compare several regimens for delivering zinc to young children, both for the prevention of zinc deficiency and the treatment of diarrhea. Methods The present study is a community-based, randomized controlled trial in the Lao People’s Democratic Republic (PDR). Three thousand, four hundred children 6–23 months of age will be randomized to one of four intervention groups (daily preventive zinc dispersible tablet, daily preventive multiple micronutrient powder, therapeutic zinc dispersible tablet for diarrhea, or placebo control); interventions will be delivered for 9 months and outcomes measured at pre-determined intervals. Primary outcomes include physical growth (length and weight), diarrhea incidence, hemoglobin and micronutrient status, and innate and adaptive immune function. Secondary outcomes include mid-upper-arm circumference, neuro-behavioral development, hair cortisol concentrations, markers of intestinal inflammation and parasite burden. Incidence of adverse events and the modifying effects of inherited hemoglobin disorders and iron status on the response to the intervention will also be examined. We will estimate unadjusted effects and effects adjusted for selected baseline covariates using ANCOVA. Discussion Many countries are now rolling out large-scale programs to include therapeutic zinc supplementation in the treatment of childhood diarrhea, but few have established programs demonstrated to be effective in the prevention of zinc deficiency. This study will address how best to deliver supplemental zinc to prevent zinc deficiency and reduce the severity of diarrhea-related health complications. Trial registration Trial registration identifier (NCT02428647) ; Date of registration: April 29, 2015.

Published
2018
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6. Benefits of small-quantity lipid-based nutrient supplements for child nutrition and survival warrant moving to scale

Author

Victor M. Aguayo, Shawn K. Baker, Kathryn G. Dewey, Emanuela Galasso, Abigail Perry, Zeina Sifri, Dina Aburmishan, Saskia de Pee, Saul I. Guerrero Oteyza, Grainne Moloney, Elizabeth L. Prado, Rahul Rawat, Linda Shaker-Berbari, Meera Shekar, Christine P. Stewart, Alison Tumilowicz, and K. Ryan Wessells

Subjects
Animal Science and Zoology, Agronomy and Crop Science, Food Science
Published
2023
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7. Insulin-like Growth Factor 1 (IGF1), IGF Binding Protein-3 (IGFBP3) and Growth Response to Daily Zinc Supplementation: A Randomized Trial in Rural Laotian Children

Author

Hess, Maxwell A. Barffour, Robin M. Bernstein, Guy-Marino Hinnouho, K. Ryan Wessells, Charles D. Arnold, Sengchanh Kounnavong, and Sonja Y.

Subjects
IGF1, IGFBP3, zinc supplementation, multiple micronutrient powder, physical growth
Abstract

Objectives: To assess (a) the impact of daily preventive zinc tablets (7 mg; PZ), zinc-containing multiple micronutrient powder (10 mg zinc, and 13 other micronutrients; MNP) or placebo, delivered for 9 months, on Insulin-like Growth Factor 1 (IGF1) and IGF Binding Protein 3 (IGFBP3) among Laotian children 6–23 months, and (b) whether the effects of PZ and MNP on length-for-age z-scores (LAZ) and weight-for-age z-scores (WAZ) are modified by baseline IGF1 and IGFBP3. Design: A double-blind, placebo-controlled trial (N = 419). Methods: Plasma IGF1 and IGFBP3 concentrations at baseline and 36 weeks were analyzed by automated chemiluminescent assay. Anthropometry was assessed at baseline, at 18 and 36 weeks. Intervention effects were estimated using ANCOVA. Results: At 36 weeks, geometric mean IGF1 (~39.0–39.2 ng/mL; p = 0.99) and IGFBP3 (2038–2076 ng/mL; p = 0.83) did not differ by group. At 18 weeks (but not at 36 weeks), LAZ in the PZ group (−1.45) was higher than the MNP (−1.70) and control (−1.55) groups (p = 0.01) among children in the highest baseline IGF1 tertile (p for interaction = 0.006). At 36 weeks (but not at 18 weeks), WAZ in the PZ group (−1.55) was significantly higher than the MNP (−1.75) and control (−1.65) groups (p = 0.03), among children in the lowest baseline IGFBP3 tertile (p for interactions = 0.06). Conclusions: Although IGF1 and IGFBP3 did not respond to PZ and MNP, baseline IGF1 and IGFBP3 significantly modified the impact of PZ on linear and ponderal growth, suggesting that IGF1 bioavailability may drive catch-up growth in zinc-supplemented children

Published
2023
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8. Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B12 status among young Laotian children: a randomized controlled trial

Author

Guy-Marino Hinnouho, Daniela Hampel, Setareh Shahab-Ferdows, Maxwell A. Barffour, Liadhan McAnena, Charles D. Arnold, K. Ryan Wessells, Sengchanh Kounnavong, Lindsay H. Allen, Helene McNulty, and Sonja Y. Hess

Subjects
Folate, and promotion of well-being, MNP, Vitamin B-12, Riboflavin, Clinical Trials and Supportive Activities, Young children, Medicine (miscellaneous), Nutritional Status, Folic Acid, Lao PDR, Clinical Research, Complementary and Integrative Health, Humans, Micronutrients, Thiamine, Child, 3.3 Nutrition and chemoprevention, Nutrition, Pediatric, Nutrition and Dietetics, Vitamin B12, Nutrition & Dietetics, Evaluation of treatments and therapeutic interventions, Vitamins, Prevention of disease and conditions, Vitamin B 12, Laos, 6.1 Pharmaceuticals, Dietary Supplements, Powders, Micronutrient powder
Abstract

Purpose To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B12 status among young Laotian children. Methods Children (n = 1704) aged 6–23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin B12 along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B12 concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline. Results There was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B12 concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B12 deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p p = 0.015). Conclusions Compared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B12 status in young Laotian children. Trial registration The trial was registered at www.clinicaltrials.gov (NCT02428647) on April 29 2015.

Published
2022

9. Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial

Author

Chidchamai, Kewcharoenwong, Myint Myint, Sein, Arnone, Nithichanon, Aranya, Khongmee, K Ryan, Wessells, Guy-Marino, Hinnouho, Maxwell A, Barffour, Sengchanh, Kounnavong, Sonja Y, Hess, Charles B, Stephensen, and Ganjana, Lertmemongkolchai

Subjects
and promotion of well-being, Multidisciplinary, Prevention, Clinical Trials and Supportive Activities, Infant, Evaluation of treatments and therapeutic interventions, Prevention of disease and conditions, Zinc, Clinical Research, Immunoglobulin G, 6.1 Pharmaceuticals, Antibody Formation, Dietary Supplements, Escherichia coli, Humans, Micronutrients, Powders, Child, 3.3 Nutrition and chemoprevention, Nutrition
Abstract

Zinc deficiency impairs the antibody-mediated immune response and is common in children from lower-income countries. This study aimed to investigate the impact of different zinc supplementation regimens (7, 10 or 20 mg/day elemental zinc)—therapeutic dispersible zinc tablets (TZ), daily multiple micronutrient powder (MNP), daily preventive zinc tablets (PZ) and placebo powder (control)—and compare between baseline and endline antibody production against pathogenic Escherichia coli in Laotian children (aged 6–23 months). Fifty representative plasma samples of each treatment group were randomly selected from 512 children to determine anti-E. coli IgG antibody levels and avidity. Of the 200 children, 78.5% had zinc deficiency (plasma zinc concentration E. coli IgG levels were significantly increased compared with baseline; the effect on the antibody level was more pronounced in children with zinc deficiency. Interestingly, there was increased anti-E. coli IgG avidity in the control and PZ groups. This study suggests that PZ might be the optimal zinc supplementation regimen to increase both the quantity and quality of antibody responses in children with zinc deficiency. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02428647 (NCT02428647, 29/04/2015).

Published
2022

10. Preventive small-quantity lipid-based nutrient supplements reduce severe wasting and severe stunting among young children: an individual participant data meta-analysis of randomized controlled trials

Author

Kathryn G. Dewey, Charles D. Arnold, K. Ryan Wessells, Elizabeth L. Prado, Souheila Abbeddou, Seth Adu-Afarwuah, Hasmot Ali, Benjamin F. Arnold, Per Ashorn, Ulla Ashorn, Sania Ashraf, Elodie Becquey, Kenneth H. Brown, Parul Christian, John M. Colford, Sherlie J. L. Dulience, Lia C.H. Fernald, Emanuela Galasso, Lotta Hallamaa, Sonja Y. Hess, Jean H. Humphrey, Lieven Huybregts, Lora L. Iannotti, Kaniz Jannat, Anna Lartey, Agnes Le Port, Jef L. Leroy, Stephen P. Luby, Kenneth Maleta, Susana L. Matias, Mduduzi NN Mbuya, Malay K. Mridha, Minyanga Nkhoma, Clair Null, Rina R. Paul, Harriet Okronipa, Jean-Bosco Ouédraogo, Amy J. Pickering, Andrew J. Prendergast, Marie Ruel, Saijuddin Shaikh, Ann M. Weber, Patricia Wolff, Amanda Zongrone, and Christine P. Stewart

Subjects
Nutrition and Dietetics, Medicine (miscellaneous)
Abstract

Background Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNS) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting. Objective We aimed to identify the effect of SQ-LNS on prevalence of severe wasting (weight-for-length z-score < -3) and severe stunting (length-for-age z-score < -3). Methods We conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. Results SQ-LNS provision led to a relative reduction of 31% in severe wasting (Prevalence Ratio, PR 0.69 (0.55, 0.86), n=34,373) and 17% in severe stunting (PR 0.83 (95% CI: 0.78, 0.90), n=36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded: PR 0.74 (0.57, 0.96), n=26,327 for severe wasting and PR 0.88 (0.81, 0.95), n=28,742 for severe stunting. Study-level characteristics generally did not significantly modify the effects of SQ-LNS, but results suggested greater effects of SQ-LNS in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation. Conclusions Including SQ-LNS in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. Registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592. This is a pre-copyedited, author-produced PDF of an article accepted for publication in The American Journal of Clinical Nutrition following peer review. The version of record [Preventive small-quantity lipid-based nutrient supplements reduce severe wasting and severe stunting among young children: an individual participant data meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition (2022)] is available online at: https://doi.org/10.1093/ajcn/nqac232. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.

Published
2022

11. Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial

Author

Sonja Y. Hess, K. Ryan Wessells, Somphou Sayasone, Guy Marino Hinnouho, Maxwell A. Barffour, Sengchanh Kounnavong, and Charles D Arnold

Subjects
Diarrhea, Male, medicine.medical_specialty, Population, Placebo, Neopterin, Gastroenterology, law.invention, Feces, chemistry.chemical_compound, Child Development, Double-Blind Method, Randomized controlled trial, law, Virology, Internal medicine, medicine, Humans, Micronutrients, education, Peroxidase, education.field_of_study, business.industry, Child Health, Infant, Articles, Micronutrient, Zinc, Infectious Diseases, chemistry, Laos, Dietary Supplements, Female, Parasitology, Calprotectin, medicine.symptom, business, Leukocyte L1 Antigen Complex, Biomarkers
Abstract

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6–23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.

Published
2020
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12. Plasma and Nail Zinc Concentrations, But Not Hair Zinc, Respond Positively to Two Different Forms of Preventive Zinc Supplementation in Young Laotian Children: a Randomized Controlled Trial

Author

David W. Killilea, Maxwell A. Barffour, Kenneth H. Brown, K. Ryan Wessells, Guy Marino Hinnouho, Sengchanh Kounnavong, Sonja Y. Hess, and Charles D Arnold

Subjects
and promotion of well-being, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Nail, Medical Biochemistry and Metabolomics, Toxicology, Biochemistry, law.invention, Plasma, 0302 clinical medicine, Randomized controlled trial, law, 030212 general & internal medicine, Micronutrients, Child, Pediatric, 0303 health sciences, General Medicine, Micronutrient, Diarrhea, Zinc, medicine.anatomical_structure, 6.1 Pharmaceuticals, Child, Preschool, Nail (anatomy), medicine.symptom, medicine.medical_specialty, Clinical Trials and Supportive Activities, chemistry.chemical_element, Placebo, Article, Inorganic Chemistry, 03 medical and health sciences, Dispersible tablet, Double-Blind Method, Clinical Research, Internal medicine, Complementary and Integrative Health, medicine, Humans, Preschool, 3.3 Nutrition and chemoprevention, Plasma zinc, Nutrition, business.industry, Prevention, Biochemistry (medical), Evaluation of treatments and therapeutic interventions, Infant, Biomarker, Prevention of disease and conditions, Endocrinology, chemistry, Nails, Dietary Supplements, Biochemistry and Cell Biology, business, Supplement, Hair
Abstract

Plasma zinc concentrations (PZC) have been shown to significantly increase during zinc supplementation. This study investigated the effects of daily preventive zinc supplementation on hair and nail zinc concentrations compared with a control group. In a randomized controlled trial, 6- to 23-month-old children (n = 3407) in Lao PDR were randomly assigned to one of four groups and followed for ~ 36 weeks: daily preventive zinc dispersible tablet (7 mg/d; PZ), daily micronutrient powder (10 mg zinc/d; MNP), therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days; TZ), or daily placebo powder (Control). Plasma, hair, and nail zinc concentrations were assessed in a sub-sample of participants (n = 457) at baseline and endline. At baseline, 75% of children had low PZC (P P = 0.99). Nail zinc concentrations were marginally higher in the PZ (115.8 (111.6, 119.9) μg/g) and the MNP (117.8 (113.3, 122.3) μg/g) groups than in the TZ group (110.4 (106.0, 114.8) μg/g; P = 0.055) at endline. This study does not support the use of hair zinc as a biomarker of zinc exposure in young children. However, it provides some evidence that zinc concentrations in nails may respond to supplemental zinc interventions and supports the need for collecting additional data on this emerging biomarker.

Published
2020

13. The cost-effectiveness of small-quantity lipid-based nutrient supplements for prevention of child death and malnutrition and promotion of healthy development: modeling results for Uganda

Author

Katherine P Adams, Stephen A Vosti, Charles D Arnold, Reina Engle-Stone, Elizabeth L Prado, Christine P Stewart, K Ryan Wessells, and Kathryn G Dewey

Abstract

ObjectiveRecent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modeling framework to estimate the cost and cost-effectiveness of SQ-LNS and apply the framework in the context of rural Uganda.DesignWe adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anemia, and developmental disability.SettingRural Uganda.ParticipantsNot applicable.ResultsProviding SQ-LNS daily to all children in rural Uganda (>1 million) for 12 months (from 6-18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars), or ∼$58.7 million annually. Annually, SQ-LNS could avert an average of >242,000 disability adjusted life years (DALYs) as a result of preventing 3,689 deaths, >160,000 cases of moderate or severe anemia, and ∼6,000 cases of developmental disability. The estimated cost per DALY averted is $242, which is considered “very cost effective” relative to the Uganda per capita GDP of $822.ConclusionsIn this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a program including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.

Published
2022
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14. Testing metal, proving mettle—findings from the 2016–2018 India Comprehensive National Nutrition Survey regarding the prevalence of low serum zinc concentrations among children and adolescents, and their implications for public health

Author

K. Ryan Wessells, Sonja Y. Hess, Christine McDonald, and Kenneth H. Brown

Subjects
medicine.medical_specialty, Nutrition and Dietetics, Adolescent, Serum zinc, business.industry, Public health, Malnutrition, MEDLINE, India, Medicine (miscellaneous), Nutrition Surveys, Zinc, Environmental health, Prevalence, Humans, Medicine, Nutrition survey, Public Health, Child, business
Published
2021
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15. Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials

Author

K. Ryan Wessells, Lotta Hallamaa, Hasmot Ali, Sonja Y. Hess, Per Ashorn, Parul Christian, Harriet Okronipa, Andrew J. Prendergast, Mduduzi N. N. Mbuya, Jean-Bosco Ouédraogo, Seth Adu-Afarwuah, Kathryn G. Dewey, Kaniz Jannat, Anna Lartey, Amy J. Pickering, Saijuddin Shaikh, Sherlie Jean Louis Dulience, Souheila Abbeddou, Marie T. Ruel, Malay K. Mridha, Emanuela Galasso, Jef L. Leroy, Clair Null, Ann M. Weber, Sania Ashraf, Jaden Bendabenda, Benjamin F. Arnold, Amanda Zongrone, Charles D Arnold, Elizabeth L. Prado, Minyanga Nkhoma, Jean H. Humphrey, Agnès Le Port, John M. Colford, Lora Iannotti, Susana L Matias, Christine P. Stewart, Lia C. H. Fernald, Lieven Huybregts, Kenneth Maleta, Kenneth H. Brown, Elodie Becquey, Patricia B. Wolff, Stephen P. Luby, Ulla Ashorn, Rina Rani Paul, University of California, Research Group on Combinatorial Algorithms and Algorithmic Graph Theory (Ghent University), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Ghana, University of Tampere [Finland], International Food Policy Research Institute [Washington] (IFPRI), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Tampere University, Department of Paediatrics, Clinical Medicine, BioMediTech, and Health Sciences

Subjects
Male, 030309 nutrition & dietetics, Psychological intervention, Medicine (miscellaneous), LOW-INCOME, Medical and Health Sciences, law.invention, AcademicSubjects/MED00160, 0302 clinical medicine, Child Development, Engineering, Randomized controlled trial, law, 3123 Gynaecology and paediatrics, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Child growth, Child, Infant Nutritional Physiological Phenomena, Wasting, OFT-FORGOTTEN PRACTICES, Randomized Controlled Trials as Topic, 2. Zero hunger, Pediatric, COMPLEMENTARY FOOD, 0303 health sciences, Bangladesh, home fortification, Nutrition and Dietetics, LINEAR GROWTH, RURAL BANGLADESH, stunting, Random effects model, Lipids, 3142 Public health care science, environmental and occupational health, WATER-QUALITY, Meta-analysis, Supplement Article, Female, Zero Hunger, Underweight, medicine.symptom, YOUNG-CHILDREN, wasting, Clinical Trials and Supportive Activities, Nutritional Status, Child Nutrition Disorders, complementary feeding, 03 medical and health sciences, AcademicSubjects/MED00060, AGE, Clinical Research, Environmental health, Nutrient supplementation, Humans, Preschool, Africa South of the Sahara, nutrient supplements, Nutrition, NUTRITIONAL SUPPLEMENTATION, Epidemiologic, Nutrition & Dietetics, business.industry, Individual participant data, Prevention, Infant, medicine.disease, Haiti, Effect Modifier, Malnutrition, Good Health and Well Being, child undernutrition, Dietary Supplements, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Demography
Abstract

Author(s): Dewey, Kathryn G; Wessells, K Ryan; Arnold, Charles D; Prado, Elizabeth L; Abbeddou, Souheila; Adu-Afarwuah, Seth; Ali, Hasmot; Arnold, Benjamin F; Ashorn, Per; Ashorn, Ulla; Ashraf, Sania; Becquey, Elodie; Bendabenda, Jaden; Brown, Kenneth H; Christian, Parul; Colford, John M; Dulience, Sherlie JL; Fernald, Lia CH; Galasso, Emanuela; Hallamaa, Lotta; Hess, Sonja Y; Humphrey, Jean H; Huybregts, Lieven; Iannotti, Lora L; Jannat, Kaniz; Lartey, Anna; Port, Agnes Le; Leroy, Jef L; Luby, Stephen P; Maleta, Kenneth; Matias, Susana L; Mbuya, Mduduzi NN; Mridha, Malay K; Nkhoma, Minyanga; Null, Clair; Paul, Rina R; Okronipa, Harriet; Ouedraogo, Jean-Bosco; Pickering, Amy J; Prendergast, Andrew J; Ruel, Marie; Shaikh, Saijuddin; Weber, Ann M; Wolff, Patricia; Zongrone, Amanda; Stewart, Christine P | Abstract: ABSTRACTBackgroundMeta-analyses have demonstrated that small-quantity lipid-based nutrient supplements (SQ-LNS) reduce stunting and wasting prevalence among infants and young children. Identification of subgroups who benefit most from SQ-LNS may facilitate program design.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child growth outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n=37,066). We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models, with random-effects models as sensitivity analyses. We used random effects meta-regression to examine study-level effect modifiers. Heterogeneity was assessed using I2 and Tau2 statistics. Sensitivity analyses were conducted to examine whether results differed depending on inclusion criteria for arms within trials and types of comparisons.ResultsSQ-LNS provision decreased stunting (length-for-age z-score l −2) by 12% (relative reduction), wasting (weight-for-length (WLZ) z-score l −2) by 14%, low mid-upper arm circumference (MUAC l 125 mm or MUACZ l −2) by 18%, acute malnutrition (WLZ l −2 or MUAC l 125 mm) by 14%, underweight (weight-for-age z-score l −2) by 13%, and small head size (head-circumference z-score l −2) by 9%. Effects of SQ-LNS on growth outcomes generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact or average reported compliance with SQ-LNS. Effects of SQ-LNS on stunting, wasting, low MUAC and small head size were greater among girls than among boys; effects on stunting, underweight and low MUAC were greater among later-born (vs. first-born) children; and effects on wasting and acute malnutrition were greater among children in households with improved (vs. unimproved) sanitation. Results were similar across sensitivity analyses.ConclusionsThe positive impact of SQ-LNS on growth is apparent across a wide variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNS in the mix of interventions to prevent both stunting and wasting. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Published
2021
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16. Lipid-based nutrient supplements and all-cause mortality in children 6–24 months of age: a meta-analysis of randomized controlled trials

Author

Lieven Huybregts, Elodie Becquey, K. Ryan Wessells, Kathryn G. Dewey, Per Ashorn, Jean H. Humphrey, Christine P. Stewart, Charles D Arnold, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, and Tampere University

Subjects
Male, medicine.medical_specialty, Psychological intervention, Medicine (miscellaneous), infants and young children, child mortality, complementary feeding, law.invention, Passive control, Child Development, Randomized controlled trial, law, Internal medicine, Risk of mortality, medicine, Humans, Terveystiede - Health care science, Infant Nutritional Physiological Phenomena, Randomized Controlled Trials as Topic, home fortification, Nutrition and Dietetics, business.industry, Malnutrition, Infant, Nutrients, Naisten- ja lastentaudit - Gynaecology and paediatrics, Lipid Metabolism, medicine.disease, Dietary Fats, Child mortality, Meta-analysis, Female, business, lipid-based nutrient supplement, All cause mortality
Abstract

Background Undernutrition is associated with an elevated risk of mortality among children in low- and middle-income countries. Small-quantity lipid-based nutrient supplements (LNS) have been evaluated as a method to prevent undernutrition and improve infant development, but the effects on mortality are unknown. Objective Our objective was to evaluate the effect of LNS on all-cause mortality among children 6-24 mo old. Methods We conducted a systematic review and meta-analysis of randomized controlled trials of LNS designed to prevent undernutrition, with or without other interventions. Literature was searched in May 2019 and trials were included if they enrolled children between 6 and 24 mo old and the period of supplementation lasted ≥6 mo. We extracted data from participant flow diagrams and contacted study investigators to request data. We conducted a meta-analysis to produce summary RR estimates. Results We identified 18 trials conducted in 11 countries that enrolled 41,280 children and reported 586 deaths. The risk of mortality was lower in the LNS arms than in the non-LNS comparison arms (RR: 0.73; 95% CI: 0.59, 0.89; 13 trials). Estimates were similar when trials with maternal LNS intervention arms were added or when alternative formulations of LNS were excluded. The results appeared stronger in trials in which LNS were compared with passive control arms. Excluding these contrasts and only comparing multicomponent arms with LNS groups and comparison groups that contained all the same components without LNS attenuated the effect estimate (RR: 0.82; 95% CI: 0.61, 1.10). Conclusions LNS provided for the prevention of undernutrition may reduce the risk of mortality, but more trials with appropriate comparison groups allowing isolation of the effect of LNS alone are needed.This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019128718.

Published
2020
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17. Small-quantity lipid-based nutrient supplements for the prevention of child malnutrition and promotion of healthy development: overview of individual participant data meta-analysis and programmatic implications

Author

K. Ryan Wessells, Kathryn G. Dewey, Christine P. Stewart, Elizabeth L. Prado, and Charles D Arnold

Subjects
Male, and promotion of well-being, Medicine (miscellaneous), Medical and Health Sciences, Child Development, Engineering, iron status, Child, Infant Nutritional Physiological Phenomena, Wasting, Randomized Controlled Trials as Topic, Pediatric, home fortification, Bangladesh, Nutrition and Dietetics, stunting, Hematology, Micronutrient, anemia, Lipids, Research Design, Zero Hunger, Female, Underweight, medicine.symptom, Anemia, wasting, Nutritional Status, Child Nutrition Disorders, complementary feeding, Environmental health, medicine, Humans, Preschool, 3.3 Nutrition and chemoprevention, nutrient supplements, Africa South of the Sahara, Metabolic and endocrine, Nutrition, Nutrition & Dietetics, business.industry, Prevention, Infant, Prevention of disease and conditions, medicine.disease, Child development, Haiti, Child mortality, undernutrition, Malnutrition, Good Health and Well Being, Iron-deficiency anemia, micronutrients, Dietary Supplements, business
Abstract

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12-14% lower prevalence of stunting, wasting, and underweight; were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.

Published
2021

18. Understanding Patterns and Drivers of Bouillon Use in Northern Ghana to Inform Fortification Planning

Author

Marjorie J Haskell, Charles D Arnold, Emily Becher, Reina Engle-Stone, Katherine P. Adams, Seth Adu-Afarwuah, Sika M Kumordzie, Jennie Davis, Ann Tarini, Stephen A. Vosti, Xiuping Tan, and K. Ryan Wessells

Subjects
Global Nutrition, Nutrition and Dietetics, Geography, Environmental health, Fortification, Medicine (miscellaneous), Gastrointestinal irritation, Micronutrient, Purchasing, Food Science, Shrimp
Abstract

OBJECTIVES: To explore the potential for bouillon as a micronutrient fortification vehicle in northern Ghana, we assessed market availability, household purchase and consumption of bouillon products, and perceptions of bouillon and salt. METHODS: We selected 28 clusters in the Tolon and Kumbungu districts of the Northern region of Ghana (7 urban, 4 semi-urban, and 3 rural clusters per district). Among 369 randomly selected households, women of reproductive age (15–49 y; WRA) were interviewed about household bouillon purchasing habits, its use in food preparation, and perceptions about the positive/negative effects of bouillon consumption. Twenty focus groups of 5–6 participants each were held in 11 clusters (10 WRA, 5 men, 5 women > 49y). We also assessed availability of bouillon products for sale from vendors in clusters (n = 11) and major markets (n = 4). RESULTS: In the survey, almost all (99%) respondents had ever cooked with bouillon, and 77% reported typically cooking with bouillon at least twice per day. Seven brands and three flavors of bouillon products were for sale. Most households (87%) reported consuming shrimp flavor without other spice most frequently. On average, households purchased bouillon cubes weekly, most from open markets (74%) or kiosks (22%). Most common reasons for bouillon use included taste (98%) and family preference (46%). Economic access was also important: 59% reported purchasing less bouillon or switching bouillon brands (28%) or flavors (11%) when they had less money available. About two-thirds of respondents perceived having bouillon in a person's diet was “good” (vs 43% for salt); reasons provided included: “gives more energy” (43%) and “makes you stronger” (41%). Among the 18% of respondents who perceived having bouillon in a person's diet was “bad”, reasons included: stomach upset (63%) and high blood pressure (39%). High blood pressure (85%) was the most common concern among the 32% perceiving salt as “bad”. Focus groups revealed seasonal variation in quantity of bouillon used. CONCLUSIONS: Bouillon consumption is common and frequent in northern Ghana, indicating good potential as a micronutrient fortification vehicle. Understanding perceptions of bouillon by different household members will inform research and program messaging. FUNDING SOURCES: Funded by a grant to the University of California, Davis from Helen Keller International.

Published
2021

19. Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B

Author

Guy-Marino, Hinnouho, Daniela, Hampel, Setareh, Shahab-Ferdows, Maxwell A, Barffour, Liadhan, McAnena, Charles D, Arnold, K, Ryan Wessells, Sengchanh, Kounnavong, Lindsay H, Allen, Helene, McNulty, and Sonja Y, Hess

Subjects
Vitamin B 12, Folic Acid, Laos, Riboflavin, Dietary Supplements, Humans, Nutritional Status, Micronutrients, Thiamine, Vitamins, Powders, Child
Abstract

To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and BChildren (n = 1704) aged 6-23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin BThere was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and BCompared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or BThe trial was registered at www.gov (NCT02428647) on April 29 2015.

Published
2021

20. Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers

Author

Emanuela Galasso, Anna Lartey, Charles D Arnold, Stephen P. Luby, Lora Iannotti, Susana L Matias, Lee S.F. Wu, Per Ashorn, Lia C. H. Fernald, Lotta Hallamaa, Ulla Ashorn, Abu Ahmed Shamim, Elizabeth Yakes Jimenez, Fahmida Tofail, Holly N. Dentz, Ann M. Weber, Sonja Y. Hess, Clair Null, Zakia Siddiqui, Lieven Huybregts, Andrew Matchado, Elizabeth L. Prado, Sarker Masud Parvez, Christine P. Stewart, Kenneth Maleta, Jaya Chandna, Elodie Becquey, Patricia L. Kohl, Sherlie Jean Louis Dulience, Kenneth H. Brown, Seth Adu-Afarwuah, Benjamin F. Arnold, Maku E. Ocansey, Agnès Le Port, Souheila Abbeddou, Robert Ntozini, Andrew J. Prendergast, K. Ryan Wessells, Amy J. Pickering, Kathryn G. Dewey, Malay K. Mridha, John Phuka, Parul Christian, University of California, University of Tampere [Finland], International Food Policy Research Institute [Washington] (IFPRI), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Male, 030309 nutrition & dietetics, Medicine (miscellaneous), Group comparison, Medical and Health Sciences, law.invention, AcademicSubjects/MED00160, Decile, Child Development, Engineering, 0302 clinical medicine, Nutrient, Randomized controlled trial, law, Medicine and Health Sciences, motor development, Medicine, 030212 general & internal medicine, Early childhood, Child, Infant Nutritional Physiological Phenomena, OFT-FORGOTTEN PRACTICES, Motor skill, Randomized Controlled Trials as Topic, Pediatric, 2. Zero hunger, Bangladesh, 0303 health sciences, Nutrition and Dietetics, Intelligence quotient, LINEAR GROWTH, RURAL BANGLADESH, HOME FORTIFICATION, Micronutrient, Random effects model, Lipids, Language development, WATER-QUALITY, Motor Skills, Meta-analysis, Zero Hunger, Female, Supplement Article, language development, YOUNG-CHILDREN, Clinical Trials and Supportive Activities, complementary feeding, AcademicSubjects/MED00060, 03 medical and health sciences, SANITATION, Clinical Research, NUTRITIONAL INTERVENTIONS, Humans, INFANT DEVELOPMENT SCORES, Preschool, Socioeconomic status, Africa South of the Sahara, nutrient supplements, Nutrition, Epidemiologic, social-emotional development, Nutrition & Dietetics, business.industry, Individual participant data, Infant, Haiti, RANDOMIZED-TRIAL, Effect Modifier, Social-emotional development, Socioeconomic Factors, executive function, child undernutrition, Dietary Supplements, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Demography
Abstract

BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) reduce child stunting and provide many of the fatty acids and micronutrients that are necessary for rapid brain development that occurs during infancy and early childhood. Positive effects of SQ-LNS on developmental outcomes have been found in some trials, but not others.ObjectivesOur objectives were to generate pooled estimates of the effect of SQ-LNS, compared to control groups that received no intervention or an intervention without any nutritional supplement, on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 intervention versus control group comparisons in 13 randomized trials of SQ-LNS provided to infants and young children age 6 to 24 months in 9 low- or middle-income countries (total n=30,024). We generated study-specific estimates of SQ-LNS vs. control groups (including main effects and subgroup estimates for individual-level effect modifiers) and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.ResultsIn 11-13 intervention versus control group comparisons (n=23,588-24,561), SQ-LNS increased mean language (mean difference: 0.07 standard deviations; 95% CI: 0.04, 0.10), social-emotional (0.08; 0.05, 0.11), and motor scores (0.08; 0.05, 0.11) and reduced the prevalence of children in the lowest decile of these scores by 17% (prevalence ratio: 0.83, 95% CI 0.76, 0.91), 19% (0.81; 0.74, 0.90), and 16% (0.84; 0.77, 0.92), respectively. SQ-LNS also increased the prevalence of children walking without support at 12 months by 9% (1.09; 1.05, 1.14). Effects of SQ-LNS on language, social-emotional, and motor outcomes were larger among study populations with a higher burden (≥ 35%) of child stunting at 18 months (mean difference 0.11-0.13 SD; 8-9 comparisons) than in populations with lower stunting burden (estimates near zero). At the individual level, greater effects of SQ-LNS were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socio-economic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).ConclusionsSQ-LNS provided daily to children in the range of 6-24 months of age can be expected to result in modest, but potentially important, developmental gains, particularly in populations with high child stunting burden. Certain groups of children who experience higher risk environments, such as those from poor households or with poor baseline nutritional status, have greater potential to benefit from SQ-LNS in developmental outcomes. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Published
2021
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21. Out-of-pocket costs and time spent attending antenatal care services: a case study of pregnant women in selected rural communities in Zinder, Niger

Author

M. Thierno Faye, Sonja Y. Hess, K. Ryan Wessells, Césaire T. Ouédraogo, Stephen A. Vosti, and Charles D Arnold

Subjects
Rural Population, medicine.medical_specialty, Antenatal care, Reproductive health and childbirth, Nursing, Time cost, Health administration, 03 medical and health sciences, 0302 clinical medicine, Library and Information Studies, Pregnancy, Clinical Research, hemic and lymphatic diseases, Health care, medicine, Humans, 030212 general & internal medicine, Niger, reproductive and urinary physiology, 030219 obstetrics & reproductive medicine, business.industry, lcsh:Public aspects of medicine, Health Policy, Public health, Nursing research, Attendance, lcsh:RA1-1270, Prenatal Care, Patient Acceptance of Health Care, medicine.disease, female genital diseases and pregnancy complications, Opportunity cost of time, Cross-Sectional Studies, Good Health and Well Being, Quartile, Public Health and Health Services, Health Policy & Services, Female, Pregnant Women, Health Expenditures, business, Demography, Research Article, Out-of-pocket costs
Abstract

Background Despite an official policy of exemption from health care costs, pregnant women in Niger still face some out-of-pocket costs (OPC) in addition to time costs when they attend antenatal care (ANC) services. We aimed to: 1) assess the OPC for pregnant woman attending ANC, 2) estimate the time spent to attend ANC and the opportunity cost of that time, and 3) assess how OPC and time spent to attend ANC affected ANC attendance. Methods Data were obtained from a quasi-experimental descriptive study carried out in the region of Zinder, Niger, which compared pre- and post-intervention cohorts of pregnant women (n = 1736 women who reported attending ANC during their current pregnancy). An ANC attendance score was developed to describe the timing of ANC attendance in regard to the WHO recommendation of attending 4 ANC sessions. OPC and time spent were evaluated separately for associations with ANC attendance using Spearman correlations. Results The mean (±SD) age of pregnant women was 25.0 ± 6.4 yr, 19.0% were ≤ 19 yr and 99.7% were in their second or third trimester of gestation at the time of the interview. Among those who were > 13 weeks and > 27 weeks of gestation, 4.0 and 74.4% had attended ANC during their first and second trimesters, respectively. The median (1st quartile (Q1), 3rd quartile (Q3)) ANC score was 0 (− 1, 0), reflecting that the majority of women failed to follow the WHO recommendation. More than half of the women (72.5%) experienced OPC related to ANC. The majority of women (> 80%) reported spending ~ 3 h for an ANC visit, including travel and waiting time. Time spent to attend ANC was not associated with ANC attendance score. Women who experienced OPC, and those who received iron folic acid (IFA) or long-lasting insecticide-treated bednets during an ANC visit, were more likely to have a higher ANC attendance score compared to those who did not. Conclusion OPC and time spent were not identified as barriers to ANC visits, and IFA and long-lasting insecticide-treated bednets distribution could be used to motivate pregnant women to attend ANC. Trial registration The NiMaNu project was registered at www.clinicaltrials.gov as NCT01832688. Registered 16 April 2013.

Published
2021

22. A multicenter analytical performance evaluation of a multiplexed immunoarray for the simultaneous measurement of biomarkers of micronutrient deficiency, inflammation and malarial antigenemia

Author

Christina M Fischer, Carine Mapango, K. Ryan Wessells, Sonja Y. Hess, Eleanor Brindle, James L. Graham, Francisco Arredondo, Crystal D Karakochuk, Lorraine Lillis, Eileen Murphy, Mikaela K Barker, Césaire T. Ouédraogo, David S. Boyle, Neal E. Craft, Christine M. Pfeiffer, Rebecca Barney, Pooja Bansil, Peter J. Havel, Jody M. Randolph, Mindy Zhang, Katherine Wander, Ei Xia Mussai, and Sebastiani, Guido

Subjects
Physiology, Organic chemistry, Biochemistry, Medicine and Health Sciences, Medicine, Multicenter Studies as Topic, Vitamin A, Immunoassay, Multidisciplinary, biology, medicine.diagnostic_test, Nutritional Deficiencies, Vitamins, C-Reactive Proteins, Micronutrient, Body Fluids, Physical sciences, Chemistry, Blood, Concordance correlation coefficient, C-Reactive Protein, Micronutrient Deficiencies, Engineering and Technology, Anatomy, Research Article, Quality Control, Analyte, General Science & Technology, Coefficient of variation, Science, Thyroglobulin, Blood Plasma, Chemical compounds, Clinical Research, Industrial Engineering, Organic compounds, Nutrition, Soluble transferrin receptor, Inflammation, Ferritin, Retinol binding protein 4, Chromatography, business.industry, Biology and Life Sciences, Protein Complexes, Proteins, Good Health and Well Being, Ferritins, biology.protein, business, Biomarkers, Software
Abstract

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at

Published
2021

23. Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials

Author

Jef L. Leroy, Rina Rani Paul, Benjamin F. Arnold, Malay K. Mridha, Emma Kortekangas, K. Ryan Wessells, Lia C. H. Fernald, Agnès Le Port, Kuda Mutasa, Harriet Okronipa, Kathryn G. Dewey, Sonja Y. Hess, Ann M. Weber, Per Ashorn, Souheila Abbeddou, Mduduzi N. N. Mbuya, Amy J. Pickering, Abu Mohd Naser, Amanda Zongrone, Christine P. Stewart, Kerry Schulze, Kenneth Maleta, Elizabeth L. Prado, Kendra A. Byrd, Rebecca Campbell, Lieven Huybregts, Audrie Lin, Elodie Becquey, Jean-Bosco Ouédraogo, Seth Adu-Afarwuah, Ulla Ashorn, Susana L Matias, Laura E. Smith, Parul Christian, Kenneth H. Brown, Emanuela Galasso, Charles D Arnold, Mahbubur Rahman, Anna Lartey, Josh M Jorgensen, Yue Mei Fan, Marion Kiprotich, University of California, Research Group on Combinatorial Algorithms and Algorithmic Graph Theory (Ghent University), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Ghana, University of Tampere [Finland], Tampere University Hospital, International Food Policy Research Institute [Washington] (IFPRI), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Tampere University, Department of Paediatrics, Clinical Medicine, and BioMediTech

Subjects
Male, and promotion of well-being, Micronutrient deficiency, COMPLEMENTARY FOODS, 030309 nutrition & dietetics, Physiology, Medicine (miscellaneous), LOW-INCOME, Medical and Health Sciences, AcademicSubjects/MED00160, 0302 clinical medicine, iron deficiency, Engineering, 3123 Gynaecology and paediatrics, Medicine and Health Sciences, 030212 general & internal medicine, Micronutrients, Child, Infant Nutritional Physiological Phenomena, OFT-FORGOTTEN PRACTICES, Randomized Controlled Trials as Topic, 2. Zero hunger, Pediatric, 0303 health sciences, education.field_of_study, home fortification, Bangladesh, Nutrition and Dietetics, biology, Anemia, Iron-Deficiency, RURAL BANGLADESH, VITAMIN-A-DEFICIENCY, Anemia, Iron deficiency, Hematology, Micronutrient, Lipids, 3. Good health, IRON-DEFICIENCY, Editorial, Nutrient supplements, Child, Preschool, Supplement Article, Female, Zero Hunger, YOUNG-CHILDREN, Home fortification, Population, Clinical Trials and Supportive Activities, Nutritional Status, Complementary feeding, anemiairon deficiency, Effect Modifier, Epidemiologic, complementary feeding, 03 medical and health sciences, AcademicSubjects/MED00060, Child undernutrition, NUTRITIONAL INTERVENTIONS, Clinical Research, Micronutrient status, RETINOL-BINDING-PROTEIN, medicine, Humans, education, Preschool, 3.3 Nutrition and chemoprevention, nutrient supplements, Africa South of the Sahara, Soluble transferrin receptor, Nutrition, Epidemiologic, Nutrition & Dietetics, business.industry, Prevention, Infant, medicine.disease, Prevention of disease and conditions, Vitamin A deficiency, Ferritin, Effect Modifier, micronutrient status, Iron-deficiency anemia, child undernutrition, Dietary Supplements, biology.protein, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Author(s): Wessells, K Ryan; Arnold, Charles D; Stewart, Christine P; Prado, Elizabeth L; Abbeddou, Souheila; Adu-Afarwuah, Seth; Arnold, Benjamin F; Ashorn, Per; Ashorn, Ulla; Becquey, Elodie; Brown, Kenneth H; Byrd, Kendra A; Campbell, Rebecca K; Christian, Parul; Fernald, Lia CH; Fan, Yue-Mei; Galasso, Emanuela; Hess, Sonja Y; Huybregts, Lieven; Jorgensen, Josh M; Kiprotich, Marion; Kortekangas, Emma; Lartey, Anna; Le Port, Agnes; Leroy, Jef L; Lin, Audrie; Maleta, Kenneth; Matias, Susana L; Mbuya, Mduduzi NN; Mridha, Malay K; Mutasa, Kuda; Naser, Abu Mohd; Paul, Rina R; Okronipa, Harriet; Ouedraogo, Jean-Bosco; Pickering, Amy J; Rahman, Mahbubur; Schulze, Kerry; Smith, Laura E; Weber, Ann M; Zongrone, Amanda; Dewey, Kathryn G | Abstract: ABSTRACTBackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to reduce the prevalence of anemia and iron deficiency among infants and young children, but effects on other micronutrients are less well known. Identifying subgroups who may experience greater benefits from SQ-LNS, or who are more likely to respond to the intervention, may facilitate the development of public health policies and programs.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child hematological and micronutrient status outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n = 15,946). Outcomes were hemoglobin (Hb), inflammation-adjusted plasma ferritin, soluble transferrin receptor, zinc, retinol and retinol binding protein (RBP), and erythrocyte zinc protoporphyrin, and respective dichotomous outcomes indicative of anemia and micronutrient deficiency. We generated study-specific estimates of SQ-LNS vs. control, including main effects and subgroup estimates for individual-level effect modifiers, and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.ResultsProvision of SQ-LNS decreased the prevalence of anemia (Hb l 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin l 12 µg/L) by 56% and iron deficiency anemia (IDA; Hb l 110 g/L and plasma ferritin l 12 µg/L) by 64%. We observed positive effects of SQ-LNS on hematological and iron status outcomes within all subgroups of the study-level and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNS on anemia and iron status were greater in trials that provided SQ-LNS for g 12 months and provided 9 mg/d vs. l 9 mg iron/d, and among later-born (vs. first-born) children. There was no effect of SQ-LNS on plasma zinc or retinol, but there was a 7% increase in plasma RBP and a 56% reduction in vitamin A deficiency (RBP l 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics.ConclusionsSQ-LNS provided to infants and young children 6-24 months of age can substantially reduce the prevalence of anemia, iron deficiency, and IDA across a range of individual, population and study design characteristics. Policy-makers and program planners should consider SQ-LNS within intervention packages to prevent anemia and iron deficiency. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Published
2021
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25. Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial

Author

Bangone Bounheuang, Sonja Y. Hess, Maxwell A. Barffour, Khanpaseuth Sengnam, Sengchanh Kounnavong, Guy-Marino Hinnouho, Bigphone Chanhthavong, Charles D Arnold, Kethmany Ratsavong, Kenneth H. Brown, K. Ryan Wessells, Charles P. Larson, and Dalaphone Sitthideth

Subjects
Male, Rural Population, and promotion of well-being, Gastroenterology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Medicine, 030212 general & internal medicine, Respiratory Tract Infections, Pediatric, Respiratory tract infections, Health Policy, Incidence (epidemiology), Incidence, Articles, Micronutrient, Diarrhea, Zinc, Infectious Diseases, Treatment Outcome, Laos, 6.1 Pharmaceuticals, Public Health and Health Services, Female, medicine.symptom, medicine.medical_specialty, Stridor, Clinical Trials and Supportive Activities, 030231 tropical medicine, chemistry.chemical_element, Placebo, 03 medical and health sciences, Double-Blind Method, Clinical Research, Internal medicine, Humans, 3.3 Nutrition and chemoprevention, Nutrition, business.industry, Prevention, Public Health, Environmental and Occupational Health, Evaluation of treatments and therapeutic interventions, Infant, Prevention of disease and conditions, Good Health and Well Being, chemistry, Dietary Supplements, Digestive Diseases, business
Abstract

BackgroundDiarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment.MethodsChildren were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models.ResultsBaseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (18 months, TZ reduced diarrhea incidence by 24% vs MNP (P = 0.035), and 36% vs Control (P = 0.004), but there was no difference with PZ. This patterned remained when analyses were restricted to diarrhea episode occurring after the first treatment with TZ. Also, in children >18 months, TZ reduced diarrhea duration by 15% vs PZ (P = 0.03), and 16% vs Control (P = 0.03), but there was no difference with MNP. There were no overall effects of study group on incidence of ALRI (overall mean 0.005 ± 0.001 episodes/100 days, P = 0.14) or AURI (overall mean 0.09 ± 0.01 episodes/100 days, P = 0.72).ConclusionsThere was no overall impact of TZ, PZ or MNP on diarrhea, ALRI and AURI. However, in children >18 months, TZ significantly reduced both the duration of diarrhea episodes and the incidence of future diarrhea episodes compared with placebo.Trial registrationClinicalTrials.gov: NCT02428647.

Published
2020

26. Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Author

Kenneth H. Brown, Sonja Y. Hess, Christine McDonald, Sanober Ismaily, Sabuktagin Rahman, K. Ryan Wessells, Frank T. Wieringa, Anne M Williams, Parminder S. Suchdev, Nancy F. Krebs, and Janet C. King

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Anemia, Medicine (miscellaneous), Nutritional Status, Inflammation, Gastroenterology, Medical and Health Sciences, AcademicSubjects/MED00160, Decile, AcademicSubjects/MED00060, Young Adult, Engineering, Internal medicine, medicine, Humans, Child, Preschool, Nutrition, Inflammation biomarkers, Supplements and Symposia, Nutrition and Dietetics, Serum zinc, Nutrition & Dietetics, business.industry, zinc, Infant, Orosomucoid, Middle Aged, medicine.disease, Micronutrient, undernutrition, Malnutrition, C-Reactive Protein, Cross-Sectional Studies, nutritional assessment, inflammation, Child, Preschool, micronutrients, Zinc deficiency, Female, medicine.symptom, business, Biomarkers
Abstract

Author(s): McDonald, Christine M; Suchdev, Parminder S; Krebs, Nancy F; Hess, Sonja Y; Wessells, K Ryan; Ismaily, Sanober; Rahman, Sabuktagin; Wieringa, Frank T; Williams, Anne M; Brown, Kenneth H; King, Janet C | Abstract: BACKGROUND:The accurate estimation of zinc deficiency at the population level is important, as it guides the design, targeting, and evaluation of nutrition interventions. Plasma or serum zinc concentration (PZC) is recommended to estimate zinc nutritional status; however, concentrations may decrease in the presence of inflammation. OBJECTIVES:We aimed to assess the relation between PZC and inflammation in preschool children (PSC; 6-59 mo) and nonpregnant women of reproductive age (WRA; 15-49 y), and to compare different inflammation adjustment approaches, if adjustment is warranted. METHODS:Cross-sectional data from 13 nationally representative surveys (18,859 PSC, 22,695 WRA) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed. Correlation and decile analyses were conducted, and the following 3 adjustment methods were compared if a consistent negative association between PZC and C-reactive protein (CRP) or α-1-acid glycoprotein (AGP) was observed: 1) exclude individuals with CRPngn5nmg/L or AGPngn1ng/L; 2) apply arithmetic correction factors; and 3) use the BRINDA regression correction (RC) approach. RESULTS:In 6 of 12 PSC surveys, the estimated prevalence of zinc deficiency increased with increasing CRP deciles, and to a lesser extent, with increasing AGP deciles. In WRA, the association of PZC with CRP and AGP was weak and inconsistent. In the 6 PSC surveys in which adjustment methods were compared, application of RC reduced the estimated prevalence of zinc deficiency by a median of 11 (range: 4-18) percentage points, compared with the unadjusted prevalence. CONCLUSIONS:Relations between PZC and inflammatory markers were inconsistent, suggesting that correlation and decile analyses should be conducted before applying any inflammation adjustments. In populations of PSC that exhibit a significant negative association between PZC and CRP or AGP, application of the RC approach is supported. At this time, there is insufficient evidence to warrant inflammation adjustment in WRA.

Published
2020

27. Impact of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Plasma Biomarkers of Environmental Enteric Dysfunction among Rural Laotian Children: A Randomized Controlled Trial

Author

Charles B. Stephensen, K. Ryan Wessells, Sonja Y. Hess, Sengchanh Kounnavong, Gertrud U. Schuster, Maxwell A. Barffour, Guy-Marino Hinnouho, Charles D Arnold, Ganjana Lertmemongkolchai, and Chidchamai Kewcharoenwong

Subjects
Diarrhea, Male, Rural Population, medicine.medical_specialty, 030231 tropical medicine, Population, chemistry.chemical_element, Zinc, Placebo, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Virology, Internal medicine, Citrulline, medicine, Humans, education, education.field_of_study, business.industry, Infant, Articles, medicine.disease, Micronutrient, Infectious Diseases, chemistry, Laos, Dietary Supplements, Zinc deficiency, Parasitology, Female, medicine.symptom, business, Kynurenine, Biomarkers
Abstract

Environmental enteric dysfunction (EED) may be ameliorated by zinc supplementation. The objective of this study was to investigate the impact of different forms of zinc supplementation on biomarkers of EED (i.e., plasma citrulline, kynurenine, and tryptophan concentrations and the kynurenine:tryptophan [KT] ratio) among young Laotian children. In a double-blind randomized controlled trial, 3,407 children aged 6–23 months were randomized into one of four groups: daily preventive zinc dispersible tablets (PZ; 7 mg zinc), daily multiple micronutrient powders (MNP; 10 mg zinc, 6 mg iron, and 13 other micronutrients), therapeutic zinc supplements for diarrhea treatment (TZ; 20 mg/day for 10 days), or daily placebo powder, and followed up for ∼36 weeks. Plasma samples at baseline and endline for 359 children were analyzed for citrulline, kynurenine, and tryptophan concentrations. At baseline, the prevalence of stunting and zinc deficiency was 37% and 76.5%, respectively. The mean plasma citrulline, kynurenine, and tryptophan concentrations were 24.6 ± 5.4 µmol/L, 3.27 ± 0.83 µmol/L, and 72.3 ± 12.9 µmol/L, respectively; the mean KT ratio (×1,000) was 45.9 ± 12.0. At endline, neither plasma citrulline, kynurenine, or tryptophan concentrations, nor the KT ratio differed among intervention groups (P > 0.05). In this population, PZ, MNP, and TZ had no overall effect on plasma concentrations of citrulline, kynurenine, and tryptophan, or the KT ratio. The need remains to better understand the etiology of EED, and the development of biomarkers to diagnose EED and evaluate the impact of interventions.

Published
2020

28. The mixed effects of a package of multilevel interventions on the health and care of pregnant women in Zinder, Niger

Author

K. Ryan Wessells, Rebecca R Young, Césaire T. Ouédraogo, M. Thierno Faye, Ibrahim Foungotin Bamba, Sonja Y. Hess, and Ndiaye Banda

Subjects
Psychological intervention, Behaviour change communication, maternal health, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Environmental health, medicine, lcsh:RC109-216, 030212 general & internal medicine, anaemia, lcsh:R5-920, business.industry, Research, 030503 health policy & services, Health Policy, Public Health, Environmental and Occupational Health, Attendance, Gestational age, nutrition, Cohort, Mixed effects, Gestation, medicine.symptom, 0305 other medical science, business, lcsh:Medicine (General), Weight gain
Abstract

BackgroundAnaemia is prevalent among pregnant women in rural Niger and antenatal care (ANC) attendance is suboptimal. We designed a programmatic intervention including community-based behaviour change communication, provision of essential drugs (including iron folic acid (IFA) supplements) and quality improvement activities at selected integrated health centres (IHCs).ObjectiveTo assess the impact of the programmatic intervention on: (1) utilisation of ANC, (2) adherence to daily IFA supplementation and (3) prevalence of adequate gestational weight gain (GWG) and anaemia among pregnant women in Zinder, Niger.MethodsUsing a quasi-experimental study design comparing a cohort of women at baseline to another cohort of women at endline, 18 IHCs and surrounding villages were randomly assigned to time of enrolment over 1 year. A baseline survey was implemented among randomly selected pregnant women in 68 village clusters. Subsequently, the intervention was rolled out and an endline survey was implemented 6 months later in the same villages.ResultsMean age in the baseline (n=1385) and endline (n=922) surveys was 25.8±6.4 years. The percentage of pregnant women who reported attending any number of ANC and an adequate number of ANC for their gestational age, respectively, was not significantly different between the endline and the baseline surveys. Pregnant women in the endline survey were more likely to have received IFA (60.0% vs 45.8%, OR: 2.7 (1.2, 6.1)); and the proportion of pregnant women who reportedly consumed IFA daily in the previous 7 days was significantly higher in the endline than in the baseline survey (46.4% vs 32.8%, OR: 2.8 (1.2, 6.5)). There was no impact on the prevalence of adequate GWG or anaemia.ConclusionsThe programmatic intervention resulted in a modest increase in the number of pregnant women who reported receiving and consuming IFA supplements as recommended, but did not affect ANC attendance and nutritional status.

Published
2019

29. Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial

Author

Charles B. Stephensen, Janet M Peerson, Maxwell A. Barffour, K. Ryan Wessells, Inthira Tussakhon, Gertrud U. Schuster, Sengchanh Kounnavong, Kenneth H. Brown, Chidchamai Kewcharoenwong, Ganjana Lertmemongkolchai, Guy-Marino Hinnouho, Sonja Y. Hess, and Waraporn Samer

Subjects
0301 basic medicine, Rural Population, medicine.medical_specialty, Lymphocyte, Medicine (miscellaneous), chemistry.chemical_element, Zinc, Placebo, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Prevalence, Medicine, Humans, Lymphocytes, Nutrition and Dietetics, medicine.diagnostic_test, business.industry, Complete blood count, Infant, Eosinophil, Micronutrient, medicine.disease, Eosinophils, Diarrhea, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, chemistry, Laos, 030220 oncology & carcinogenesis, Dietary Supplements, Zinc deficiency, medicine.symptom, business, Deficiency Diseases
Abstract

Author(s): Kewcharoenwong, Chidchamai; Schuster, Gertrud U; Wessells, K Ryan; Hinnouho, Guy-Marino; Barffour, Maxwell A; Kounnavong, Sengchanh; Brown, Kenneth H; Hess, Sonja Y; Samer, Waraporn; Tussakhon, Inthira; Peerson, Janet M; Lertmemongkolchai, Ganjana; Stephensen, Charles B | Abstract: BACKGROUND:Zinc deficiency impairs immune function and is common among children in South-East Asia. OBJECTIVES:The effect of zinc supplementation on immune function in young Laotian children was investigated. METHODS:Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration). RESULTS:T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL, P = 0.012). CONCLUSIONS:Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647.

Published
2019

30. Impact of Preventive and Therapeutic Zinc Supplements on Citrulline Concentration and the kynurenine: tryptophan Ratio Among Lao Children: A Randomized Controlled Trial (OR07-02-19)

Author

Kenneth H. Brown, Somphou Sayasone, K. Ryan Wessells, Guy-Marino Hinnouho, Sonja Y. Hess, Maxwell A. Barffour, Charles D Arnold, and Sengchanh Kounnavong

Subjects
Global Nutrition, Nutrition and Dietetics, business.industry, Tryptophan, Medicine (miscellaneous), Pharmacology, medicine.disease, Micronutrient, law.invention, chemistry.chemical_compound, chemistry, Plasma drug concentration, Randomized controlled trial, law, Zinc deficiency, medicine, Citrulline, business, Kynurenine, Food Science, Zinc Supplements
Abstract

OBJECTIVES: To investigate the impact of different forms of zinc supplementation on plasma citrulline (CIT), kynurenine (KYN) and tryptophan (TRP) concentrations and the kynurenine: tryptophan ratio (KTR), considered as markers of intestinal function and systemic inflammatory response, among young Lao children. METHODS: In a randomized controlled double-blind trial, 3407 children aged 6–23 mo were randomized into one of four groups and followed for ∼36 weeks: daily preventive zinc dispersible tablet (7 mg zinc; PZ), daily multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP), therapeutic zinc supplements for the treatment of diarrhea (20 mg/d for 10 days with each diarrhea episode; TZ), or daily placebo powder (Control). Plasma samples at baseline and endline for 359 children participating in the parent trial were analyzed at the NIH West Coast Metabolomics Center (UC Davis); plasma CIT, KYN and TRP concentrations were determined by hydrophilic interaction chromatography (HILIC) quadrupole time of flight mass spectrometer (QTOF) tandem mass spectrometry (MS/MS). Linear regression models were used to assess the treatment effect, controlling for baseline value, child age and district. RESULTS: The parent trial found no overall group-wise effects on linear growth or diarrhea outcomes. In the subgroup included in the present analyses, mean age at enrollment was 16.0 ± 4.9 mo, 37% were stunted and 83% were zinc deficient. At baseline, mean plasma CIT, KYN and TRP concentrations were 24.6 ± 5.4 µM, 3.27 ± 0.83 µM and 72.3 ± 12.9 µM, respectively; the mean KT ratio was 0.046 ± 0.013. 5% of children had low CIT (

Published
2019

31. Exogenous Phytase Added to Lipid Based Nutrient Supplements Increases Fractional and Total Absorption of Zinc Among Young Gambian Children: A Randomized Controlled Trial (OR07-01-19)

Author

Andrew M. Prentice, K. Ryan Wessells, Kenneth H. Brown, Kabiru Ceesay, Rita Wegmüller, Sarah J Zyba, and Leslie R. Woodhouse

Subjects
Global Nutrition, Nutrition and Dietetics, Chemistry, Medicine (miscellaneous), chemistry.chemical_element, Zinc, Absorption (skin), law.invention, Nutrient, Animal science, Randomized controlled trial, law, medicine, Phytase, Underweight, medicine.symptom, Food Science
Abstract

OBJECTIVES: Dietary phytate inhibits zinc absorption from composite meals in adults. The objective of this study was to investigate the efficacy of adding exogenous phytase to a small-quantity lipid based nutrient supplement (SQ-LNS) on zinc absorption among young children. METHODS: In a double-blind randomized controlled trial, intra-individual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from SQ-LNS with and without phytase were measured in 30 asymptomatic 18–23 month old children in the Kiang West district of The Gambia. Using a cross-over design, children received for one day each test meals of a millet-based porridge with 20 g SQ-LNS containing 8 mg zinc and either: 1) exogenous phytase (∼500 phytase units (FTU)) or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a dual-stable isotope tracer ratio technique with (67) Zn and (70) Zn as oral tracers, randomized independently of SQ-LNS product, and (68) Zn as the intravenous tracer. TAZ was calculated as the product of total dietary zinc (TDZ) intake from test meals (i.e., porridge, SQ-LNS and stable isotope) and FAZ. FAZ and TAZ were compared for meals with and without phytase using mixed-models ANOVA with product, study day, and oral isotope allocation as fixed effects and individual child as a random effect. RESULTS: Twenty-six participants completed the study. The prevalence of stunting, underweight and wasting were 20%, 30% and 13%, respectively; no children had low plasma zinc concentrations (

Published
2019

32. Effect of exogenous phytase added to small-quantity lipid-based nutrient supplements (SQ-LNS) on the fractional and total absorption of zinc from a millet-based porridge consumed with SQ-LNS in young Gambian children: a randomized controlled trial

Author

Kabiru Ceesay, Leslie R. Woodhouse, Andrew M. Prentice, K. Ryan Wessells, Rita Wegmüller, Sarah J Zyba, and Kenneth H. Brown

Subjects
Male, Phytic Acid, Medicine (miscellaneous), chemistry.chemical_element, Absorption (skin), Zinc, law.invention, Nutrient, Animal science, Randomized controlled trial, law, medicine, Humans, Micronutrients, Millets, Wasting, 6-Phytase, Nutrition and Dietetics, Chemistry, Infant, Lipid Metabolism, Crossover study, Lipids, Phytase activity, Dietary Supplements, Phytase, Female, Food Additives, Gambia, medicine.symptom
Abstract

BACKGROUND Dietary phytate inhibits zinc absorption from composite meals in adults. OBJECTIVE The objective of this study was to investigate the effect of adding exogenous phytase to a small-quantity lipid-based nutrient supplement (SQ-LNS) on zinc absorption among young children. METHODS In a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from a millet-based porridge containing SQ-LNS with and without phytase were measured in 30 asymptomatic children 18-23 mo of age in the Kiang West district of The Gambia. Using a crossover design, children received for 1 d each porridge test meals with 20 g SQ-LNS containing 8 mg zinc and either 1) exogenous phytase or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a triple stable isotope tracer ratio technique with Zn-67 and Zn-70 as oral tracers and Zn-68 as the intravenous tracer. RESULTS Twenty-six participants completed the study. The prevalence of stunting and wasting were 20% and 13%, respectively; no children had low plasma zinc concentrations (

Published
2019

33. Dietary Consumption Patterns and Their Predictors Among Young Children in Northern Ghana

Author

Reina Engle-Stone, Emily Becher, Stephen A. Vosti, Sika M Kumordzie, K. Ryan Wessells, Jennie Davis, Marjorie J Haskell, Katherine P. Adams, Charles D Arnold, Xiuping Tan, and Seth Adu-Afarwuah

Subjects
Global Nutrition, Consumption (economics), Food insecurity, Nutrition and Dietetics, Geography, Environmental health, digestive, oral, and skin physiology, Physical activity, food and beverages, Medicine (miscellaneous), Food Science
Abstract

OBJECTIVES: To assess the prevalence and frequency of consumption of vegetables, fruits, sugar sweetened beverages (SSBs), salty and sweet snacks and the relationship between consumption and household characteristics (residence location, food insecurity, and socioeconomic status [SES]) among children 2–5 years of age in two districts in the Northern region of Ghana. METHODS: Households were recruited from 14 urban, 8 semi-urban and 6 rural clusters in the Tolon and Kumbungu districts in Northern Ghana. Primary caregivers of children 2–5 years (n = 242) reported the number of days in a typical week selected food items were consumed, and the number of servings per day. Household characteristics, food insecurity (USAID Household Food Insecurity Access Scale) and SES, were assessed via questionnaires administered to the head of household. We examined the relationships between consumption of each food and 1) residence (urban vs. semi-urban/rural), 2) household food insecurity (moderate/severe vs. none/mild) and 3) household SES (lowest quartile vs. other quartiles). RESULTS: The proportion of children who consumed each food in a typical week was: 98% vegetables, 81% sweet snacks, and 75% fruits; approximately half of children consumed salty snacks (51%) or SSBs (46%). Mean (SD) servings consumed in a typical week were: 7.85 (7.32) vegetables, 2.82 (2.51) sweet snacks, 2.54 (3.69) SSBs, 1.77 (1.70) fruits, and 1.17 (1.67) salty snacks. Consumption of fruits (82% vs 68%, p = 0.01) and sweet snacks (91% vs 71%, p

Published
2021
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34. Analyses Using National Survey Data From Cameroon, Haiti, and Ghana Indicate the Potential for Bouillon Fortification to Help Fill Dietary Gaps for 5 Nutrients

Author

Reina Engle-Stone, Ismael Teta, K. Ryan Wessells, Alex Ndjebayi, Marjorie J Haskell, Stephen A. Vosti, Katherine P. Adams, Seth Adu-Afarwuah, Sika M Kumordzie, Yves-Laurent Régis, and Hanqi Luo

Subjects
Global Nutrition, Dietary iron, Nutrition and Dietetics, Cost effectiveness, Fortification, Medicine (miscellaneous), Micronutrient, Geography, Nutrient, Folic acid, Environmental health, Survey data collection, Vitamin B12, Food Science
Abstract

OBJECTIVES: We modeled the potential impacts of bouillon fortification with different levels of vitamin A, folic acid, vitamin B12, iron, and zinc on dietary micronutrient adequacy to inform multi-stakeholder discussions around bouillon fortification programs. METHODS: We used individual dietary intake data in Cameroon from women of reproductive age (WRA) and children 1–5 y (n = 902 and 872), and household (HH) survey data in Cameroon (n = 11,384 HH), Ghana (n = 11,870 HH), and Haiti (n = 4,951 HH) to estimate micronutrient (MN) intake. The Adult Male Equivalent method was applied to estimate “apparent intake” of WRA, children, and men from HH surveys. We examined intake of bouillon and calculated prevalence of inadequate (below the estimated average requirement) and high (above the tolerable upper intake level, UL) micronutrient intake. Analyses included the contributions of mandatory fortification of oil or wheat flour at estimated current micronutrient levels. We simulated the impacts of bouillon fortification with varying levels of vitamin A, folic acid, vitamin B12, iron, and zinc on inadequate and high intakes of each nutrient. RESULTS: Bouillon was commonly consumed in all countries, with any reported consumption ranging from 67–81% in Ghana to over 90% in Cameroon and Haiti. Median (apparent) bouillon consumption ranged from 1.6–2.1 g/d for women, 0.7–1.0 g/d for children, and 1.8–2.2 g/d for men. Bouillon fortification with vitamins was predicted to reduce dietary inadequacy (120 μg/g vitamin A: 15–33 percentage points, pp, depending on the country and target group; 80 μg/g folate: 11–33 pp; 1.2 μg/g B12: 12–67 pp) with minimal risk of high intake. In contrast, predicted effects on dietary iron inadequacy were modest (5–12 pp reduction at 5 mg iron/g, assuming 2% absorption). Simulated zinc fortification showed reductions in inadequate absorbable zinc intake (14–42 pp at 3 mg/g), but children's intakes commonly exceeded the UL. CONCLUSIONS: Modeling suggests that bouillon fortification could reduce inadequate MN intakes in these countries. Further work is needed to identify fortification levels that will meet criteria for nutritional benefits, technical feasibility, and cost-effectiveness. FUNDING SOURCES: This analysis was supported by a grant to UC Davis from Helen Keller International.

Published
2021
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35. Urinary iodine concentration identifies pregnant women as iodine deficient yet school-aged children as iodine sufficient in rural Niger

Author

K. Ryan Wessells, Michael B. Zimmermann, Sonja Y. Hess, Rebecca R Young, Césaire T. Ouédraogo, Sara Stinca, and Ibrahim Foungotin Bamba

Subjects
Male, Rural Population, 0301 basic medicine, Thyrotropin, Medicine (miscellaneous), 0302 clinical medicine, Pregnancy, Salt iodization, Prevalence, Medicine, Niger, Child, Dried blood, Family Characteristics, education.field_of_study, Nutrition and Dietetics, School age child, Research Papers, Female, Iodine, Adult, medicine.medical_specialty, Population, Nutritional Status, chemistry.chemical_element, 030209 endocrinology & metabolism, Thyroglobulin, Young Adult, 03 medical and health sciences, Environmental health, Internal medicine, Humans, Sodium Chloride, Dietary, education, 030109 nutrition & dietetics, Dose-Response Relationship, Drug, business.industry, Pregnancy Complications, Hematologic, Public Health, Environmental and Occupational Health, medicine.disease, Iodine deficiency, Spot urine sample, Thyroxine, Cross-Sectional Studies, Endocrinology, Socioeconomic Factors, chemistry, Sample Size, Dried Blood Spot Testing, Urinary iodine, business, Follow-Up Studies
Abstract

ObjectiveTo assess iodine status among pregnant women in rural Zinder, Niger and to compare their status with the iodine status of school-aged children from the same households.DesignSeventy-three villages in the catchment area of sixteen health centres were randomly selected to participate in the cross-sectional survey.SettingSalt iodization is mandatory in Niger, requiring 20–60 ppm iodine at the retail level.SubjectsA spot urine sample was collected from randomly selected pregnant women (n662) and one school-aged child from the same household (n373). Urinary iodine concentration (UIC) was assessed as an indicator of iodine status in both groups. Dried blood spots (DBS) were collected from venous blood samples of pregnant women and thyroglobulin (Tg), thyroid-stimulating hormone and total thyroxine were measured. Iodine content of household salt samples (n108) was assessed by titration.ResultsMedian iodine content of salt samples was 5·5 ppm (range 0–41 ppm), 98 % had an iodine content 40 µg/l.ConclusionsIn this region of Niger, most salt is inadequately iodized. UIC in pregnant women indicated iodine deficiency, whereas UIC of school-aged children indicated marginally adequate iodine status. Thus, estimating population iodine status based solely on monitoring of UIC among school-aged children may underestimate the risk of iodine deficiency in pregnant women.

Published
2016
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36. Prevalence and determinants of gestational weight gain among pregnant women in Niger

Author

M. Thierno Faye, K. Ryan Wessells, Rebecca R Young, Sonja Y. Hess, and Césaire T. Ouédraogo

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Adolescent, Epidemiologic Factors, Nutritional Status, Guidelines as Topic, Logistic regression, 03 medical and health sciences, Hemoglobins, Young Adult, 0302 clinical medicine, Interquartile range, Pregnancy, medicine, Prevalence, Humans, 030212 general & internal medicine, Niger, 030109 nutrition & dietetics, Nutrition and Dietetics, Obstetrics, business.industry, Public Health, Environmental and Occupational Health, Obstetrics and Gynecology, Gestational age, weight gain, Maternal Nutritional Physiological Phenomena, Original Articles, medicine.disease, Micronutrient, Gestational Weight Gain, undernutrition, Malnutrition, Pediatrics, Perinatology and Child Health, Gestation, low income countries, Female, Original Article, Pregnant Women, medicine.symptom, business, Weight gain, Biomarkers, maternal nutrition
Abstract

Low gestational weight gain (GWG) and low mid‐upper arm circumference (MUAC) are associated with adverse pregnancy outcomes. We aimed to assess the prevalence and determinants of low GWG and low MUAC among pregnant women in rural Zinder, Niger. A community‐based survey was conducted among 1,384 pregnant women in the catchment areas of 18 integrated health centers in the region of Zinder, Niger. Weight and MUAC were measured during an in‐home visit and again 1 month later, when haemoglobin concentration and micronutrient status were also assessed. The prevalence of low GWG was defined based on the 2009 United States Institute of Medicine (U.S. IOM) guidelines (

Published
2019

37. Assessment of Dietary Intake and Nutrient Gaps, and Development of Food-Based Recommendations, among Pregnant and Lactating Women in Zinder, Niger: An Optifood Linear Programming Analysis

Author

Sonja Y. Hess, Rebecca R Young, Elaine L. Ferguson, K. Ryan Wessells, Césaire T. Ouédraogo, and M. Thierno Faye

Subjects
0301 basic medicine, and promotion of well-being, food-based recommendations, Riboflavin, Recommended Dietary Allowances, Cardiovascular, Optifood, chemistry.chemical_compound, 0302 clinical medicine, Nutrient, Pregnancy, Medicine, 030212 general & internal medicine, Micronutrients, Niger, 2. Zero hunger, Meal, education.field_of_study, Nutrition and Dietetics, Retinol, linear programming, Programming, Linear, deficiency, Micronutrient, Programming, Female, women, lcsh:Nutrition. Foods and food supply, Vitamin, Population, Nutritional Status, lcsh:TX341-641, lactation, Linear, Article, 03 medical and health sciences, Food Sciences, Environmental health, pregnant, Complementary and Integrative Health, Humans, micronutrient, education, 3.3 Nutrition and chemoprevention, Metabolic and endocrine, Nutrition, 030109 nutrition & dietetics, business.industry, Prevention, Feeding Behavior, Maternal Nutritional Physiological Phenomena, medicine.disease, Prevention of disease and conditions, Diet, chemistry, business, Energy Intake, dietary intake, Food Science
Abstract

Pregnant and lactating women in rural Niger are at high risk for inadequate intakes of multiple micronutrients. Thus, 24 h dietary recalls were conducted and analyzed for dietary intakes in this population (n = 202). Using linear programming analyses, micronutrient gaps in women&rsquo, s diets were identified, food-based recommendations (FBR) to improve dietary micronutrient adequacy were developed, and various supplementation strategies were modelled. Energy intakes were below estimated requirements, and, for most micronutrients, &gt, 50% of women were at risk of inadequate intakes. Linear programming analyses indicated it would be difficult to select a diet that achieved recommended dietary allowances for all but three (vitamin B6, iron and zinc) of 11 modeled micronutrients. Consumption of one additional meal per day, and adherence to the selected FBR (daily consumption of dark green leafy vegetables, fermented milk, millet, pulses, and vitamin A fortified oil), would result in a low percentage of women at risk of inadequate intakes for eight modeled micronutrients (vitamin A, riboflavin, thiamin, B6, folate, iron, zinc, and calcium). Because the promotion of realistic FBRs likely will not ensure that a low percentage of women are at risk of inadequate intakes for all modeled micronutrients, multiple micronutrient supplementation or provision of nutrient-dense foods should be prioritized.

Published
2019

38. Impact of Two Forms of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Hair Cortisol Concentrations Among Rural Laotian Children: A Randomized Controlled Trial

Author

Guy-Marino, Hinnouho, Robin M, Bernstein, Maxwell A, Barffour, Charles D, Arnold, K Ryan, Wessells, Kethmany, Ratsavong, Bangone, Bounheuang, Sengchanh, Kounnavong, and Sonja Y, Hess

Subjects
Diarrhea, Male, Rural Population, young children, MNP, Hydrocortisone, zinc supplementation, Infant, digestive system diseases, Article, Zinc, micronutrient powder, Lao PDR, Double-Blind Method, Laos, Risk Factors, Stress, Physiological, Dietary Supplements, hair cortisol, Humans, Female, Hair, chronic stress
Abstract

Zinc supplementation has been shown to reduce the morbidity burden among young children, and may reduce chronic stress. Hair cortisol has been promoted as an indicator of chronic stress. We assessed the impact of different strategies for delivering supplementary zinc on hair cortisol concentrations (HCC) in young Laotian children and examined risk factors associated with HCC. In a randomized double-blind controlled trial (NCT02428647), children aged 6–23 mo were randomized to one of four intervention groups and followed for ~36 weeks: daily preventive zinc (PZ) tablets (7 mg/day), daily multiple micronutrient powder (MNP) sachets (containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days) or daily placebo powder. HCC of 512 children was assessed at baseline and endline. ANCOVA and linear regression models were used to assess group differences in HCC and to examine the risk factors associated with HCC, respectively. At enrollment, mean HCC was 28.8 ± 43.9 pg/mg. In models adjusted for age at enrollment, health district, and baseline HCC there was no overall effect of the interventions on endline HCC and change in HCC. When controlling for additional predetermined covariates, there was a marginally significant effect on change in HCC (p = 0.075) with a slightly lower reduction of HCC in TZ compared to PZ (mean change (95% CI): −4.6 (−7.0; −2.3) vs. −9.4 (−11.7; −7.0) pg/mg; p = 0.053). At baseline, consumption of iron rich foods was negatively associated with HCC, whereas AGP (α1-acid glycoprotein) levels, elevated AGP and C-reactive protein and high soluble transferrin receptor were positively associated with HCC. In young Laotian children, MNP, PZ and TZ had no impact on HCC. The marginal difference in change in HCC between the PZ and TZ groups was too small to be considered of health significance.

Published
2018

39. Within-individual differences in plasma ferritin, retinol-binding protein, and zinc concentrations in relation to inflammation observed during a short-term longitudinal study are similar to between-individual differences observed cross-sectionally

Author

K. Ryan Wessells, Kenneth H. Brown, and Janet M Peerson

Subjects
Male, medicine.medical_specialty, Longitudinal study, Medicine (miscellaneous), Nutritional Status, Internal medicine, medicine, Prevalence, Humans, Longitudinal Studies, Micronutrients, Soluble transferrin receptor, Inflammation, Nutrition and Dietetics, biology, business.industry, Acute-phase protein, Repeated measures design, Infant, Reproducibility of Results, Orosomucoid, Ferritin, Retinol-Binding Proteins, Retinol binding protein, Zinc, Endocrinology, C-Reactive Protein, Cross-Sectional Studies, Nutrition Assessment, Research Design, Ferritins, biology.protein, Population study, Female, Geometric mean, business, Deficiency Diseases
Abstract

Background Cross-sectional (CS) surveys indicate that individuals with acute inflammation have higher plasma ferritin (pF), and lower retinol-binding protein (RBP) and zinc (pZn) concentrations than those without. In populations with a high burden of infection, correction factors (CFs) or regression corrections (RCs) are applied to biomarkers to estimate the prevalence of micronutrient (MN) deficiencies adjusted for inflammation. This assumes that individuals with and without inflammation have the same nutritional status, which may not be the case. Objectives The aim of this study was to investigate relations between short-term, longitudinal within-individual changes in acute phase proteins (C-reactive protein [CRP], α-1-acid glycoprotein [AGP]) and biomarkers of MN status (pF, soluble transferrin receptor [sTfR], RBP, and pZn), and compare them to CS differences. Methods Two blood samples were obtained 21 d apart from 451 asymptomatic Burkinabe children aged 6-23 mo. To calculate CFs, inflammation was defined as CRP >5 mg/L or AGP >1 g/L, or both. The RC approach adjusted MN biomarkers to a presumably healthy reference point within the study population (10th percentile CRP or AGP concentration). CS CFs and RCs were estimated from a naive regression model, treating observations from the same children as independent. Longitudinal CFs and RCs, to estimate effects of within-individual changes in CRP and/or AGP, were estimated from general linear models, accounting for repeated measures. Results In CS models, geometric mean pF and sTfR concentrations were 8-340% greater, and RBP and pZn 2-18% lower, in children with inflammation than those without. Except for sTfR, biomarker concentrations differed in the same direction and by similar magnitude within individuals whose inflammation status changed during the observation period. Although geometric mean MN concentrations differed significantly when adjusted with CS compared with longitudinal models, the estimated prevalence of MN deficiencies in CS and longitudinally adjusted models was similar. Conclusions The CF and RC approaches to adjust MN biomarkers for inflammation between individuals in CS surveys are valid approaches for data collection and programmatic decisions in comparable populations. This study was registered at clinicaltrials.gov as NCT00944853.

Published
2018

40. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013

Author

Yong Zhao, Hadi Danawi, Bach Xuan Tran, Gene Bukhman, Vasiliki Stathopoulou, Taavi Tillmann, Nelson Alvis-Guzman, Yongmei Li, Jerry Puthenpurakal Abraham, Sudan Prasad Neupane, Jack Caravanos, Ben Schöttker, Rafael Lozano, Damian G Hoy, Yoshihiro Kokubo, Nicholas J K Breitborde, Sergey Soshnikov, Yukito Shinohara, Randall V. Martin, Michael Brainin, Fernando Perez-Ruiz, Yingfeng Zheng, Santosh Mishra, Julio Cesar Montañez Hernandez, Michael Phillips, Belinda J. Gabbe, Hebe N. Gouda, Ziad A. Memish, Rupert R A Bourne, Guoqing Hu, Emmanuel A. Ameh, Abigail McLain, Michelle L. Bell, Christopher Margono, Marissa Iannarone, Wilkister N. Moturi, Donald H. Silberberg, Carl Abelardo T. Antonio, Nataliya Foigt, Anand Dayama, Yanping Wang, Amanda J. Mason-Jones, Bolajoko O. Olusanya, Monica S. Vavilala, Katherine B Gibney, David Tanne, Sidibe S Kany Roseline, Marcella Montico, Abhishek Singh, Sarah Derrett, Alireza Esteghamati, Seok Jun Yoon, Corine Karema, Rakhi Dandona, David M. Pereira, Kazem Rahimi, Gitanjali M. Singh, Vivekanand Jha, John Hornberger, Anne M. Riederer, Kathryn H. Jacobsen, Andrea Pedroza, Lily Alexander, Fiona M. Blyth, Tommi Vasankari, Kyle J Foreman, Rana J. Asghar, Tilahun Nigatu Haregu, Yousef Khader, Rafael Alfonso-Cristancho, Suzanne Barker-Collo, Lydia S. Atkins, Simerjot K. Jassal, Mohammad Ali Sahraian, Peter Scarborough, Hans W. Hoek, E. Ray Dorsey, Muluken Dessalegn, David C. Schwebel, Gavin Shaddick, Thomas D. Fleming, Mohammad Tavakkoli, Dorairaj Prabhakaran, Mohammad H. Forouzanfar, Christopher C. Mapoma, Jost B. Jonas, Erin C Mullany, Gene F. Kwan, Johanna M. Geleijnse, Antonio Luiz Pinho Ribeiro, Roberto Tchio Talongwa, Tolesa Bekele, Jed D. Blore, Gunn Marit Aasvang, Philimon Gona, Miguel Angel Alegretti, Babak Eshrati, Mitsuru Mukaigawara, Richard F. Gillum, Odgerel Chimed-Ochir, Ubai Alsharif, Richard C. Franklin, Felix Masiye, Richard T. Burnett, Sanjay Krishnaswami, Martin McKee, John J Huang, Lucía Cuevas-Nasu, Wagner Marcenes, Walid Ammar, Knud Juel, Joseph R. Zunt, Martha M Téllez Rojo, Mamta Swaroop, Noela M Prasad, Azmeraw T. Amare, Tim Driscoll, Michael Kravchenko, Heresh Amini, Amir Sapkota, Theo Vos, Charlotte Watts, Dennis Odai Laryea, D. Alex Quistberg, Justin Beardsley, Cheng Huang, Adnan M. Durrani, Sarah V Thackway, Rita Van Dingenen, Manami Inoue, Martha Híjar, Honglei Chen, Amany H. Refaat, Yichong Li, Vineet K. Chadha, Wenzhi Wang, Louisa Degenhardt, Kingsley N. Ukwaja, Nayu Ikeda, James D. Wilkinson, Linh N Bui, Maria Hagströmer, Gonghuan Yang, Ann Kristin Knudsen, David J. Margolis, Soewarta Kosen, Hans Kromhout, Atsushi Goto, Man Mohan Mehndiratta, Thomas N. Williams, Michael Soljak, Yun Jin Kim, Hideaki Toyoshima, Jeyaraj D Pandian, Borja del Pozo-Cruz, Soufiane Boufous, Ivy Shiue, Anders Larsson, Guilherme V. Polanczyk, John Powles, Yara A. Halasa, Robin Room, Ratilal Lalloo, Carolina Batis Ruvalcaba, Panniyammakal Jeemon, Elisabete Weiderpass, Jürgen Rehm, Ejaz Ahmad Khan, Alicia Aleman, Zacharie Tsala Dimbuene, Elena Alvarez, Rachelle Buchbinder, Randah R. Hamadeh, Bryan Hubbell, Sadaf G. Sepanlou, Farhad Islami, Costas A. Christophi, Heidi Stöckl, Ismael R. Campos-Nonato, Nigel Bruce, Edward J Mills, Samuel A L Perry, Taavi Lai, Baffour Awuah, Mete Saylan, Karen J. Courville, Arindam Basu, Vanessa De la Cruz-Góngora, Teresita González de Cosío, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Muluken Azage Yenesew, Atte Meretoja, Michael Brauer, Cyrus Cooper, Giorgia Giussani, Valentina S. Arsic Arsenijevic, Vasiliy Victorovich Vlassov, André Karch, Leilei Duan, Matthew M Coates, Omid Ameli, Gelin Xu, Matthias Endres, Ganesan Karthikeyan, Ione Jayce Ceola Schneider, Mohamed Hsairi, Palwasha Anwari, Mazin J. Al Khabouri, Dariush Mozaffarian, Juan R. Sanabria, Pablo M. Lavados, Sumeet S. Chugh, Johan Ärnlöv, Ivo Rakovac, Maurice Giroud, Haidong Kan, Ibrahim Abdelmageem Mohamed Ginawi, José Luis Texcalac-Sangrador, Luigi Naldi, Erica Leigh Slepak, Deena Alasfoor, James E. Saunders, Richard Matzopoulos, Talal Bakfalouni, Stein Emil Vollset, Andrea Werdecker, Lennert J. Veerman, Lorenzo Monasta, Henrica A. F. M. Jansen, Reyna A Gutiérrez, Brittany Wurtz, Luz Maria Sanchez, Lijing L. Yan, M. Patrice Lindsay, Michele Meltzer, Sanjay Basu, Steven van de Vijver, Alaa Badawi, Thomas Claßen, Young-Ho Khang, Brett M. Kissela, Jun Zhu, In-Hwan Oh, Fiona J Charlson, Maria Cecilia Bahit, Dinorah González-Castell, Rosario Cárdenas, Dan Poenaru, Sayed Saidul Alam, Mitchell T. Wallin, Harish Chander Gugnani, James Leigh, Ferrán Catalá-López, Lidia Morawska, Jim van Os, Stephanie J. London, Kaire Innos, Isabelle Romieu, Fiorella Cavalleri, Adrian Davis, Hwee Pin Phua, Chakib Nejjari, Héctor Gómez Dantés, Boris I. Pavlin, Karen Sliwa, Lynne Gaffikin, Constance D. Pond, Michael F. MacIntyre, Blake Thomson, Norberto Perico, Ronny Westerman, Samantha M. Colquhoun, Michael H. Criqui, Ana Maria Nogales Vasconcelos, Wubegzier Mekonnen, Bulat Idrisov, Ana Basto-Abreu, Andrew G. M. Bulloch, Jasvinder A. Singh, Vinod K. Paul, Emin Murat Tuzcu, Svetlana Popova, Hmwe H Kyu, Richard L. Guerrant, Mohammed I. Albittar, Srikanth Mangalam, Steven E. Lipshultz, Lela Sturua, Semaw Ferede Abera, Eduardo Bernabé, George D. Thurston, Bruno F. Sunguya, Tiffany Ku, Alejandra G. Contreras, Abdullah Sulieman Terkawi, Charles Atkinson, Ashkan Afshin, Heidi J. Larson, Abdullatif Husseini, Jose C. Adsuar, Reza Assadi, Ademola Lukman Adelekan, Joshua A. Salomon, Yousef M. Elshrek, Gokalp Kadri Yentur, Devina Nand, Narayanaswamy Venketasubramanian, Graça Maria Ferreira De Lima, Maheswar Satpathy, Fotis Topouzis, Traolach S. Brugha, Hywel C Williams, Coen H. Van Gool, Andrew H. Kemp, Awoke Misganaw, Amado D Quezada, Norito Kawakami, Bert Brunekreef, Peter Burney, Tati S. Warouw, Jongmin Lee, Inga Dora Sigfusdottir, Marcel Tanner, Solveig A. Cunningham, Benjamin O. Anderson, Tariku Jibat Beyene, Lars Barregard, Xia Wan, Giuseppe Remuzzi, Bernadette Thomas, Lilia S Pedraza, Massimo Cirillo, Alina Rodriguez, Ricky Leung, Farshad Pourmalek, K. Srinath Reddy, Charles D.A. Wolfe, Ulrich O Mueller, Neeraj Bedi, Al Artaman, Lucia Hernandez, Itamar S. Santos, C. Arden Pope, Norlinah Mohamed Ibrahim, Carlo Irwin A. Panelo, Selen Begüm Uzun, Miltiadis K. Tsilimbaris, Anwar Rafay, Daniel Dicker, Melvin Barrientos Marzan, Sajjad Ur Rahman, Mohammed O. Basulaiman, Edgar P. Simard, Mohammad T Mashal, Maysaa El Sayed Zaki, Shiwei Liu, Don C. Des Jarlais, Bo Norrving, Salvador Villalpando, Miia Kivipelto, Yang Liu, Carolina Maria Teixeira, Catalina Medina, Sudha Jayaraman, Josep Maria Haro, Diego De Leo, Angel J Paternina Caicedo, Abigail C. McKay, Eric L. Ding, Mukesh Dherani, Ljiljana Pejin Stokic, Vinay Nangia, Sukanta Saha, Juan Liang, Elisabeth Cardis, Zourkaleini Younoussi, José R Nogueira, Braden Te Ao, Vasco Manuel Pedro Machado, Lionel Racapé, Ting Wu Chuang, Shahab Khatibzadeh, E Filipa de Castro, Barthelemy Kuate Defo, Ulises Trujillo, Alan D. Lopez, Soraya Seedat, Lope H Barrero, Linhong Wang, Daniel Pope, Alexandra Brazinova, Faris Lami, Valentina Colistro, G Anil Kumar, Derek F J Fay, Haidong Wang, Hwashin H. Shin, Raimundas Lunevicius, Suzanne Polinder, Dietrich Plass, David Rojas-Rueda, Stephen S Lim, Tania G Sánchez-Pimienta, K.M. Venkat Narayan, Yuantao Hao, Jung-Chen Chang, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Luciano A. Sposato, Stan Biryukov, Kunihiro Matsushita, Beth E. Ebel, Cleusa P. Ferri, Soumya Swaminathan, K. Ryan Wessells, Gustavo Velasquez-Melendez, Leslie T. Cooper, David O. Carpenter, Nancy Lopez, Bryan L. Sykes, Sandra Nolte, Murray B. Stein, Paul N. Jensen, Fabiola Mejía-Rodríguez, Xiaonong Zou, Bradford D. Gessner, Dhruv S. Kazi, Dragos Virgil Davitoiu, Alejandra Jáuregui, Pouria Heydarpour, Megan Bohensky, Harvey Whiteford, Berrak Bora Basara, Zhengming Chen, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Nima Hafezi-Nejad, John Nelson Opio, Scott Weichenthal, Deborah Salvo, Jun She, Tea Lallukka, Carolyn C. Gotay, Stephen G. Waller, Christian Kieling, Shivanthi Balalla, Valery L. Feigin, Qing Lan, Matias Trillini, Adam D M Briggs, Sungroul Kim, Niveen M E Abu-Rmeileh, Renata Micha, Sergey Petrovich Ermakov, Ole Frithjof Norheim, Zulfiqar A Bhutta, Paul S. F. Yip, Grant Nguyen, Ralph L. Sacco, Biju Abraham, Ken Takahashi, Jixiang Ma, Peter A. Meaney, Ayse Abbasoglu Ozgoren, Kimberly Cooperrider, M Rifat Kose, Shams Eldin Ali Hassan Khalifa, Rasmus Havmoeller, Alize J. Ferrari, Kebede Deribe, Nadim E. Karam, George A. Mensah, Bongani M. Mayosi, Konrad Pesudovs, Joanna Moschandreas, Ziad Nahas, James Damsere-Derry, Nsanzimana Sabin, Tonatiuh Barrientos-Gutiérrez, Ying Jiang, Andre Pascal Kengne, Peter Allebeck, Jonas Minet Kinge, Shankuan Zhu, Guy B. Marks, Daniel C Casey, Marco A Avila, Anna Roca, Lalit Dandona, Ami R. Moore, Adansi A. Amankwaa, David Gunnell, Andre Keren, Yohannes Adama Melaku, Nhung T Nguyen, Anthony D. Woolf, Mayuree Rao, Peter J. Allen, Christina Papachristou, Karzan Abdulmuhsin Mohammad, Ravi Kumar Balu, Marie Ng, Marcello Tonelli, Maziar Moradi-Lakeh, Maigeng Zhou, Emmanuela Gakidou, Mohammed K. Ali, Amanda W Pain, Dan J. Stein, Kawkab Shishani, Fortuné Gbètoho Gankpé, Howard J. Hoffman, James Scott, Nadine Steckling, Samia Alhabib, Deborah Jarvis, Kara Estep, Arsène Kouablan Adou, Ricardo Orozco, Holly Hagan, K. C. Astha, Reza Malekzadeh, Klara Dokova, Aliya Naheed, Ernst J. Kuipers, Valeria Caso, Derrick A Bennett, Andrea B. Feigl, Uche S. Uchendu, Holly E. Erskine, Shireen Sindi, Arjun Lakshmana Balaji, Francesco Saverio Violante, Monika Sawhney, Alejandra Cantoral, Ketevan Goginashvili, Raghib Ali, Fan Jiang, Robert G. Weintraub, Homie Razavi, Myriam Tobollik, Howard Hu, Emerito Jose A. Faraon, Irma Khonelidze, Patricia M. Riccio, Eun-Kee Park, Julio Cesar Campuzano, Ibrahim Abubakar, Jürgen C Schmidt, Konstantinos Stroumpoulis, Aref A. Bin Abdulhak, Graeme J. Hankey, Natan M. Bornstein, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Alanur Çavlin, Ruth W Kimokoti, Samir Soneji, Mark J. Nieuwenhuijsen, John Q. Wong, Joseph Frostad, Tom Achoki, Rahman Shiri, Ashish Bhalla, Kurt Straif, Simon I. Hay, Scott B. Patten, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Chandrashekhar T Sreeramareddy, Ryan M Barber, Rosana E. Norman, JianLi Wang, Siyi Shangguan, Luke Nyakarahuka, Kovin Naidoo, Charles D. H. Parry, Mercedes Colomar, H. Ross Anderson, Carlos Magis-Rodriguez, Joan M. Nolla, Muhammad Imran Nisar, Karen Devries, Andrew L. Thorne-Lyman, Denis Nash, Marape Marape, Rajiv Chowdhury, Dima M. Qato, Luca Ronfani, Nobhojit Roy, Daniel Kim, Yuichiro Yano, Luke D. Knibbs, Margaret Robinson, Hilda L Harb, Rogelio Pérez-Padilla, Janet L Leasher, Jonathan L. Wright, Peter Brooks, Cristiana Abbafati, Belinda K Lloyd, Victor Aboyans, Nikhil Tandon, Charles R. Newton, Simón Barquera, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Glen Mola, Paulo A. Lotufo, Burcu Kucuk Bicer, Peggy Pei-Chia Chiang, Alexander Kraemer, Solomon Meseret Woldeyohannes, Saman Fahimi, Lesley Rushton, Kim Moesgaard Iburg, Vafa Rahimi-Movaghar, Logan Sandar, Bruce Neal, Teresa Shamah Levy, Karen M. Tabb, Jeffrey A. Towbin, Christopher J L Murray, Ramesh Sahathevan, Aaron Cohen, Chanda Kulkarni, Van C. Lansingh, François Alla, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Uchechukwu K.A. Sampson, Rajeev Gupta, Neil Pearce, Mustafa Z. Younis, Veena S. Kulkarni, Francisco A García-Guerra, Amanda G. Thrift, Stefan Ma, Samaya Ismayilova, Evariste Gasana, Amitava Banerjee, Aslam Pervaiz, Emilie Agardh, Abraham D. Flaxman, Farshad Farzadfar, Peter W. Gething, Ileana Heredia-Pi, Boris Bikbov, Wanqing Chen, Saad B. Omer, Ruben Castro, Neeraj Bhala, Sara Sheikhbahaei, Hilton Lam, Urbano Fra Paleo, Lidia Sanchez-Riera, Alicia Elena Beatriz Lawrynowicz, Kristen Delwiche, Richard G. Ellenbogen, Max Petzold, Yuri Y Varakin, Guilherme Borges, Guohong Jiang, Francis Guillemin, Kyle R. Heuton, Yohannes Kinfu, Victoria F Bachman, Joseph A Wagner, Carlos A Castañeda-Orjuela, Leonardo Trasande, Abbas Ali Mahdi, Josef Coresh, Chuanhua Yu, Kenji Shibuya, Berrin Serdar, Laetitia Huiart, Xiaofeng Liang, Jean de Dieu Ngirabega, Takayoshi Ohkubo, Natalie Stephens, Francis Apolinary Mhimbira, Jefferson Traebert, Amiran Gamkrelidze, Kjetil Søreide, Samath D Dharmaratne, Robert P. Dellavalle, George Mugambage Ruhago, Lakshmi Vijayakumar, Joannie Lortet-Tieulent, Dipan Bose, Tania C Aburto, Saleem M Rana, Miriam Levi, Mohammad Taghi Hedayati, Rodolfo S Pagcatipunan, Ron T. Gansevoort, H. D. Hosgood, Michael Burch, Mohsen Naghavi, Vegard Skirbekk, Ayfer Pekericli, Walter Mendoza, Pengpeng Ye, Gabrielle deVeber, Ali H. Mokdad, David M. Broday, Koranteng Adofo, Zewdie Aderaw Alemu, Shifalika Goenka, Carrie Beth Peterson, Nicolas J. C. Stapelberg, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Giancarlo Logroscino, Kardiyoloji, Peterson, Carrie B., Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Wisconsin Division of Public Health, Laboratoire de psychologie sociale et de psychologie cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), London South Bank University, Metropolitan Police Service, Hong Kong Baptist University (HKBU), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Insight Centre for Data Analytics [Galway] (INSIGHT), National University of Ireland [Galway] (NUI Galway), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institute, karolinska institute, Department of Molecular Biosciences, Department of Molecular Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Computer Science Department [Bristol], University of Bristol [Bristol], Universität Mannheim [Mannheim], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Computational Science and Engineering Department [Daresbury] (STFC), Science & Technologie Facilities Council, Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, University of Southampton, Imperial College London, Neurology Department, Ichilov Medical Center, Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Risk Assessment Sciences Institute, Utrecht University [Utrecht], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Respiratory Epidemiology and Public Health, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], CIBER de Epidemiología y Salud Pública (CIBERESP), STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Tennent Institute of Ophthalmology, National University of Singapore (NUS), Centre de Robotique (CAOR), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Multidisciplinary Nanotechnology Centre, Swansea University, Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Genomics Research Center, Academia Sinica, Neuro Rehab Services LLP [New Delhi], Department of Signal Theory and Communications (TSC), Univ. Politec. de Catalunya, King‘s College London, Dept. Mat. Engn. De Ma, Sao Carlos, Fed. Univ. Sao Carlos UFSCar, RESPEC (RESPEC), RESPEC, Advanced Laboratories on Embedded Systems [Roma] (ALES), Department of Biology [Miami], University of Miami [Coral Gables], Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Department of Nephrology, University Medical Center, University of Groningen, Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] (WUR), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], College of Medicine, University of Hail, Saudi Arabia, Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] (UPC), Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University-Shahid Beheshti University, Center for Applied Medical Research (CIMA), University of Tehran, Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, George Washington University (GW), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent [Ghent], Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Fachbereich Physik [Berlin], Freie Universität Berlin, Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), Univ New Delhi, School of Physics and Astronomy, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center (TRDDC), TCS Innovation Labs, University of Helsinki, Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency (FOI), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Novartis Pharmaceutical Corporation, Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble [1985-2015] (OSUG [1985-2015]), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Centre d'études et de recherche en informatique et communications (CEDRIC), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), College of Information and Electrical Engineering [Beijing] (CIEE), China Agricultural University (CAU), Thales Research and Technology [Palaiseau], THALES, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), École supérieure du professorat et de l'éducation - Académie de Grenoble [2013-2019] (ESPE Grenoble [2013-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, Pennsylvania State University (Penn State), Penn State System-Penn State System, University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], American University of Beirut [Beyrouth] (AUB), Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Mailman School of Public Health, Columbia University [New York], The Georges Institute for International Health, The University of Sydney, Department of epidemiology and Public Health, Faculty of Medicine, Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université de la Méditerranée - Aix-Marseille 2, Department of Neurology Lunds University Hospital Lund, Unit of Functional Bionanomaterials, School of Biosciences, University of Birmingham [Birmingham], Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], World Health Organization, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Nordic School of Public Health, The James Hutton Institute, Horia Hulubei National Institute for Physics and Nuclear Engineering, Department of Pediatrics, University of Washington [Seattle], Institute of Public Health, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Dept.of Computer Science, Indian Institute of Technology Madras (IIT Madras), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut geològic de Catalunya (IGC), Institut Geològic de Catalunya-IGC, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Politecnico di Milano [Milan] (POLIMI), Symantec, University of Oviedo, European Microsoft Innovation Center (EMIC), Microsoft Corporation [Redmond, Wash.], Technion - Israel Institute of Technology [Haifa], Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Department of Physics, Cavendish Laboratory, University of Cambridge [UK] (CAM), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling (CMM), Department of Global Health and Development, London School of Hygiene and Tropical Medicine (LSHTM), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Universidade Federal de Pernambuco [Recife] (UFPE), Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute (NEST), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology (LICB), JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC), Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] (LNCC / MCT), Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] (KTH ), NICTA [Eveleigh], National ICT Australia [Sydney] (NICTA), Division of Solid Mechanics, Lund University [Lund], University of Calgary, BioWare Corp, Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Imaging Sciences and Biomedical Engineering Division [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Neurorestoration Group, Wolfson Centre for Age-related Diseases-King‘s College London, Electronic Navigation Research Institute (ENRI), Ministry of Land, Infrastructure, Transport and Tourism, Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Centre for Undergraduate Studies, University of the Punjab, Siemens Corporate Research, Siemens AG [Munich], University of Massachusetts [Boston] (UMass Boston), University of Massachusetts System (UMASS), Department of Materials Science, Sichuan University [Chengdu] (SCU), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Shahid Beheshti University of Medical Sciences, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH)-Universidad del Desarrollo, Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), École supérieure du professorat et de l'éducation - Académie de Grenoble (ESPE Grenoble), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), California Institute of Technology (CALTECH)-NASA, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), King‘s College London-Wolfson Centre for Age-related Diseases, Sichuan University, Universitat de Barcelona, Interne Geneeskunde, Medische Sociologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatrie & Neuropsychologie, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), RS: MHeNs - R2 - Mental Health, Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de psychologie sociale et de psychologie cognitive ( LAPSCO ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Erosion torrentielle neige et avalanches ( UR ETGR ), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture ( IRSTEA ), Hong Kong Baptist University ( HKBU ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Insight Centre for Data Analytics (National University of Ireland Galway (NUIG)) ( INSIGHT ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Oslo ( UiO ) -University of Oslo ( UiO ), Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Computational Science and Engineering Department [Daresbury] ( STFC ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], University of Southampton [Southampton], Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University Medical Center Utrecht, Biologie Fonctionnelle et Adaptative ( BFA ), Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), National University of Singapore ( NUS ), Centre de Robotique ( CAOR ), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University ( PSL ), Department of Signal Theory and Communications ( TSC ), RESPEC ( RESPEC ), Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Wageningen University and Research Centre [Wageningen] ( WUR ), Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Freie Universität Berlin [Berlin], Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Tata Research Development and Design Center ( TRDDC ), Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Swedish Defense Research Agency ( FOI ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Novartis Pharmaceutical Corp., East Hanover NJ 07936, USA, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mechanical and Automation Engineering ( CAD Laboratory ), National Institutes of Health ( NIH ), Centre d'étude et de recherche en informatique et communications ( CEDRIC ), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise ( ENSIIE ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), College of Information and Electrical Engineering [Beijing] ( CIEE ), China Agricultural University ( CAU ), Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), École supérieure du professorat et de l'éducation - Académie de Grenoble ( ESPE Grenoble ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Université Grenoble Alpes ( UGA ), PennState University [Pennsylvania] ( PSU ), Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), American University of Beirut [Beyrouth], The University of Sydney [Sydney], Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Laboratoire des signaux et systèmes ( L2S ), Université Paris-Sud - Paris 11 ( UP11 ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Center for Research in Environmental Epidemiology ( CREAL ), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Indian Institute of Technology Madras ( IIT Madras ), Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Laboratoire de Génie Informatique et Ingénierie de Production ( LGI2P ), IMT - Mines Alès Ecole Mines - Télécom ( IMT - MINES ALES ), Institut geològic de Catalunya ( IGC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physiologie et Génomique des Poissons ( LPGP ), Institut National de la Recherche Agronomique ( INRA ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Politecnico di Milano [Milan], European Microsoft Innovation Center ( EMIC ), Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), University of Cambridge [UK] ( CAM ), Laboratoire de Probabilités et Modèles Aléatoires ( LPMA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), London School of Hygiene and Tropical Medicine ( LSHTM ), University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Universidade Federal de Pernambuco [Recife] ( UFPE ), Nanoscience Institute ( NEST ), Laboratory Of Immune Cell Biology ( LICB ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ), Bonn Universität [Bonn], Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] ( LNCC / MCT ), Royal Institute of Technology [Stockholm] ( KTH ), National ICT Australia [Sydney] ( NICTA ), Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), Children’s Hospital of Philadelphia ( CHOP ), Univeristy of Pennsylvania Medical School, Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Medical College of Georgia, Electronic Navigation Research Institute ( ENRI ), Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), University of Massachusetts [Boston] ( UMass Boston ), Forouzanfar, Mohammad H, Alexander, Lily, Anderson, H. Ro, Bachman, Victoria F, Biryukov, Stan, Brauer, Michael, Burnett, Richard, Casey, Daniel, Coates, Matthew M, Cohen, Aaron, Delwiche, Kristen, Estep, Kara, Frostad, Joseph J, Kc, Astha, Kyu, Hmwe H, Moradi Lakeh, Maziar, Ng, Marie, Slepak, Erica Leigh, Thomas, Bernadette A, Wagner, Joseph, Aasvang, Gunn Marit, Abbafati, Cristiana, Ozgoren, Ayse Abbasoglu, Abd Allah, Foad, Abera, Semaw F, Aboyans, Victor, Abraham, Biju, Abraham, Jerry Puthenpurakal, Abubakar, Ibrahim, Abu Rmeileh, Niveen M. E, Aburto, Tania C, Achoki, Tom, Adelekan, Ademola, Adofo, Koranteng, Adou, Arsène K, Adsuar, José C, Afshin, Ashkan, Agardh, Emilie E, Al Khabouri, Mazin J, Al Lami, Faris H, Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I, Alegretti, Miguel A, Aleman, Alicia V, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Ali, Mohammed K, Alla, Françoi, Allebeck, Peter, Allen, Peter J, Alsharif, Ubai, Alvarez, Elena, Alvis Guzman, Nelson, Amankwaa, Adansi A, Amare, Azmeraw T, Ameh, Emmanuel A, Ameli, Omid, Amini, Heresh, Ammar, Walid, Anderson, Benjamin O, Antonio, Carl Abelardo T, Anwari, Palwasha, Cunningham, Solveig Argeseanu, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J, Assadi, Reza, Atkins, Lydia S, Atkinson, Charle, Avila, Marco A, Awuah, Baffour, Badawi, Alaa, Bahit, Maria C, Bakfalouni, Talal, Balakrishnan, Kalpana, Balalla, Shivanthi, Balu, Ravi Kumar, Banerjee, Amitava, Barber, Ryan M, Barker Collo, Suzanne L, Barquera, Simon, Barregard, Lar, Barrero, Lope H, Barrientos Gutierrez, Tonatiuh, Basto Abreu, Ana C, Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O, Ruvalcaba, Carolina Bati, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L, Benjet, Corina, Bennett, Derrick A, Benzian, Habib, Bernabé, Eduardo, Beyene, Tariku J, Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A, Bikbov, Bori, Abdulhak, Aref A. Bin, Blore, Jed D, Blyth, Fiona M, Bohensky, Megan A, Başara, Berrak Bora, Borges, Guilherme, Bornstein, Natan M, Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R, Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J, Brenner, Hermann, Briggs, Adam D. M, Broday, David M, Brooks, Peter M, Bruce, Nigel G, Brugha, Traolach S, Brunekreef, Bert, Buchbinder, Rachelle, Bui, Linh N, Bukhman, Gene, Bulloch, Andrew G, Burch, Michael, Burney, Peter G. J, Campos Nonato, Ismael R, Campuzano, Julio C, Cantoral, Alejandra J, Caravanos, Jack, Cárdenas, Rosario, Cardis, Elisabeth, Carpenter, David O, Caso, Valeria, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chen, Honglei, Chen, Wanqing, Chen, Zhengming, Chiang, Peggy P, Chimed Ochir, Odgerel, Chowdhury, Rajiv, Christophi, Costas A, Chuang, Ting Wu, Chugh, Sumeet S, Cirillo, Massimo, Claßen, Thomas Kd, Colistro, Valentina, Colomar, Mercede, Colquhoun, Samantha M, Contreras, Alejandra G, Cooper, Cyru, Cooperrider, Kimberly, Cooper, Leslie T, Coresh, Josef, Courville, Karen J, Criqui, Michael H, Cuevas Nasu, Lucia, Damsere Derry, Jame, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dargan, Paul I, Davis, Adrian, Davitoiu, Dragos V, Dayama, Anand, de Castro, E. Filipa, De la Cruz Góngora, Vanessa, De Leo, Diego, de Lima, Graça, Degenhardt, Louisa, Del Pozo Cruz, Borja, Dellavalle, Robert P, Deribe, Kebede, Derrett, Sarah, Jarlais, Don C. De, Dessalegn, Muluken, Deveber, Gabrielle A, Devries, Karen M, Dharmaratne, Samath D, Dherani, Mukesh K, Dicker, Daniel, Ding, Eric L, Dokova, Klara, Dorsey, E. Ray, Driscoll, Tim R, Duan, Leilei, Durrani, Adnan M, Ebel, Beth E, Ellenbogen, Richard G, Elshrek, Yousef M, Endres, Matthia, Ermakov, Sergey P, Erskine, Holly E, Eshrati, Babak, Esteghamati, Alireza, Fahimi, Saman, Faraon, Emerito Jose A, Farzadfar, Farshad, Fay, Derek F. J, Feigin, Valery L, Feigl, Andrea B, Fereshtehnejad, Seyed Mohammad, Ferrari, Alize J, Ferri, Cleusa P, Flaxman, Abraham D, Fleming, Thomas D, Foigt, Nataliya, Foreman, Kyle J, Paleo, Urbano Fra, Franklin, Richard C, Gabbe, Belinda, Gaffikin, Lynne, Gakidou, Emmanuela, Gamkrelidze, Amiran, Gankpé, Fortuné G, Gansevoort, Ron T, García Guerra, Francisco A, Gasana, Evariste, Geleijnse, Johanna M, Gessner, Bradford D, Gething, Pete, Gibney, Katherine B, Gillum, Richard F, Ginawi, Ibrahim A. M, Giroud, Maurice, Giussani, Giorgia, Goenka, Shifalika, Goginashvili, Ketevan, Dantes, Hector Gomez, Gona, Philimon, de Cosio, Teresita Gonzalez, González Castell, Dinorah, Gotay, Carolyn C, Goto, Atsushi, Gouda, Hebe N, Guerrant, Richard L, Gugnani, Harish C, Guillemin, Franci, Gunnell, David, Gupta, Rahul, Gupta, Rajeev, Gutiérrez, Reyna A, Hafezi Nejad, Nima, Hagan, Holly, Hagstromer, Maria, Halasa, Yara A, Hamadeh, Randah R, Hammami, Mouhanad, Hankey, Graeme J, Hao, Yuantao, Harb, Hilda L, Haregu, Tilahun Nigatu, Haro, Josep Maria, Havmoeller, Rasmu, Hay, Simon I, Hedayati, Mohammad T, Heredia Pi, Ileana B, Hernandez, Lucia, Heuton, Kyle R, Heydarpour, Pouria, Hijar, Martha, Hoek, Hans W, Hoffman, Howard J, Hornberger, John C, Hosgood, H. Dean, Hoy, Damian G, Hsairi, Mohamed, Hu, Guoqing, Hu, Howard, Huang, Cheng, Huang, John J, Hubbell, Bryan J, Huiart, Laetitia, Husseini, Abdullatif, Iannarone, Marissa L, Iburg, Kim M, Idrisov, Bulat T, Ikeda, Nayu, Innos, Kaire, Inoue, Manami, Islami, Farhad, Ismayilova, Samaya, Jacobsen, Kathryn H, Jansen, Henrica A, Jarvis, Deborah L, Jassal, Simerjot K, Jauregui, Alejandra, Jayaraman, Sudha, Jeemon, Panniyammakal, Jensen, Paul N, Jha, Vivekanand, Jiang, Fan, Jiang, Guohong, Jiang, Ying, Jonas, Jost B, Juel, Knud, Kan, Haidong, Roseline, Sidibe S. Kany, Karam, Nadim E, Karch, André, Karema, Corine K, Karthikeyan, Ganesan, Kaul, Anil, Kawakami, Norito, Kazi, Dhruv S, Kemp, Andrew H, Kengne, Andre P, Keren, Andre, Khader, Yousef S, Khalifa, Shams Eldin Ali Hassan, Khan, Ejaz A, Khang, Young Ho, Khatibzadeh, Shahab, Khonelidze, Irma, Kieling, Christian, Kim, Daniel, Kim, Sungroul, Kim, Yunjin, Kimokoti, Ruth W, Kinfu, Yohanne, Kinge, Jonas M, Kissela, Brett M, Kivipelto, Miia, Knibbs, Luke D, Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kose, M. Rifat, Kosen, Soewarta, Kraemer, Alexander, Kravchenko, Michael, Krishnaswami, Sanjay, Kromhout, Han, Ku, Tiffany, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kuipers, Ernst J, Kulkarni, Chanda, Kulkarni, Veena S, Kumar, G. Anil, Kwan, Gene F, Lai, Taavi, Balaji, Arjun Lakshmana, Lalloo, Ratilal, Lallukka, Tea, Lam, Hilton, Lan, Qing, Lansingh, Van C, Larson, Heidi J, Larsson, Ander, Laryea, Dennis O, Lavados, Pablo M, Lawrynowicz, Alicia E, Leasher, Janet L, Lee, Jong Tae, Leigh, Jame, Leung, Ricky, Levi, Miriam, Li, Yichong, Li, Yongmei, Liang, Juan, Liang, Xiaofeng, Lim, Stephen S, Lindsay, M. Patrice, Lipshultz, Steven E, Liu, Shiwei, Liu, Yang, Lloyd, Belinda K, Logroscino, Giancarlo, London, Stephanie J, Lopez, Nancy, Lortet Tieulent, Joannie, Lotufo, Paulo A, Lozano, Rafael, Lunevicius, Raimunda, Ma, Jixiang, Ma, Stefan, Machado, Vasco M. P, Macintyre, Michael F, Magis Rodriguez, Carlo, Mahdi, Abbas A, Majdan, Marek, Malekzadeh, Reza, Mangalam, Srikanth, Mapoma, Christopher C, Marape, Marape, Marcenes, Wagner, Margolis, David J, Margono, Christopher, Marks, Guy B, Martin, Randall V, Marzan, Melvin B, Mashal, Mohammad T, Masiye, Felix, Mason Jones, Amanda J, Matsushita, Kunihiro, Matzopoulos, Richard, Mayosi, Bongani M, Mazorodze, Tasara T, Mckay, Abigail C, Mckee, Martin, Mclain, Abigail, Meaney, Peter A, Medina, Catalina, Mehndiratta, Man Mohan, Mejia Rodriguez, Fabiola, Mekonnen, Wubegzier, Melaku, Yohannes A, Meltzer, Michele, Memish, Ziad A, Mendoza, Walter, Mensah, George A, Meretoja, Atte, Mhimbira, Francis Apolinary, Micha, Renata, Miller, Ted R, Mills, Edward J, Misganaw, Awoke, Mishra, Santosh, Ibrahim, Norlinah Mohamed, Mohammad, Karzan A, Mokdad, Ali H, Mola, Glen L, Monasta, Lorenzo, Hernandez, Julio C. Montañez, Montico, Marcella, Moore, Ami R, Morawska, Lidia, Mori, Rintaro, Moschandreas, Joanna, Moturi, Wilkister N, Mozaffarian, Dariush, Mueller, Ulrich O, Mukaigawara, Mitsuru, Mullany, Erin C, Murthy, Kinnari S, Naghavi, Mohsen, Nahas, Ziad, Naheed, Aliya, Naidoo, Kovin S, Naldi, Luigi, Nand, Devina, Nangia, Vinay, Narayan, Km Venkat, Nash, Deni, Neal, Bruce, Nejjari, Chakib, Neupane, Sudan P, Newton, Charles R, Ngalesoni, Frida N, de Dieu Ngirabega, Jean, Nguyen, Grant, Nguyen, Nhung T, Nieuwenhuijsen, Mark J, Nisar, Muhammad I, Nogueira, José R, Nolla, Joan M, Nolte, Sandra, Norheim, Ole F, Norman, Rosana E, Norrving, Bo, Nyakarahuka, Luke, Oh, In Hwan, Ohkubo, Takayoshi, Olusanya, Bolajoko O, Omer, Saad B, Opio, John Nelson, Orozco, Ricardo, Pagcatipunan, Rodolfo S, Pain, Amanda W, Pandian, Jeyaraj D, Panelo, Carlo Irwin A, Papachristou, Christina, Park, Eun Kee, Parry, Charles D, Caicedo, Angel J. 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Srinath, Refaat, Amany H, Rehm, Jürgen, Remuzzi, Giuseppe, Ribeiro, Antonio L, Riccio, Patricia M, Richardson, Lee, Riederer, Anne, Robinson, Margaret, Roca, Anna, Rodriguez, Alina, Rojas Rueda, David, Romieu, Isabelle, Ronfani, Luca, Room, Robin, Roy, Nobhojit, Ruhago, George M, Rushton, Lesley, Sabin, Nsanzimana, Sacco, Ralph L, Saha, Sukanta, Sahathevan, Ramesh, Sahraian, Mohammad Ali, Salomon, Joshua A, Salvo, Deborah, Sampson, Uchechukwu K, Sanabria, Juan R, Sanchez, Luz Maria, Sánchez Pimienta, Tania G, Sanchez Riera, Lidia, Sandar, Logan, Santos, Itamar S, Sapkota, Amir, Satpathy, Maheswar, Saunders, James E, Sawhney, Monika, Saylan, Mete I, Scarborough, Peter, Schmidt, Jürgen C, Schneider, Ione J. C, Schöttker, Ben, Schwebel, David C, Scott, James G, Seedat, Soraya, Sepanlou, Sadaf G, Serdar, Berrin, Servan Mori, Edson E, Shaddick, Gavin, Shahraz, Saeid, Levy, Teresa Shamah, Shangguan, Siyi, She, Jun, Sheikhbahaei, Sara, Shibuya, Kenji, Shin, Hwashin H, Shinohara, Yukito, Shiri, Rahman, Shishani, Kawkab, Shiue, Ivy, Sigfusdottir, Inga D, Silberberg, Donald H, Simard, Edgar P, Sindi, Shireen, Singh, Abhishek, Singh, Gitanjali M, Singh, Jasvinder A, Skirbekk, Vegard, Sliwa, Karen, Soljak, Michael, Soneji, Samir, Søreide, Kjetil, Soshnikov, Sergey, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stapelberg, Nicolas J. 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Ryan, Westerman, Ronny, Whiteford, Harvey A, Wilkinson, James D, Williams, Hywel C, Williams, Thomas N, Woldeyohannes, Solomon M, Wolfe, Charles D. A, Wong, John Q, Woolf, Anthony D, Wright, Jonathan L, Wurtz, Brittany, Xu, Gelin, Yan, Lijing L, Yang, Gonghuan, Yano, Yuichiro, Ye, Pengpeng, Yenesew, Muluken, Yentür, Gökalp K, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok Jun, Younis, Mustafa Z, Younoussi, Zourkaleini, Yu, Chuanhua, Zaki, Maysaa E, Zhao, Yong, Zheng, Yingfeng, Zhou, Maigeng, Zhu, Jun, Zhu, Shankuan, Zou, Xiaonong, Zunt, Joseph R, Lopez, Alan D, Vos, Theo, Murray, Christopher J., Cell biology, Epidemiology, Neurosciences, Health Technology Assessment (HTA), Public Health, General practice, Bachman, Victoria F., Coates, Matthew M., Frostad, Joseph J., Astha, K.C., Kyu, Hmwe H., Moradi-Lakeh, Maziar, Thomas, Bernadette A., Abbasoglu Ozgoren, Ayse, Abd-Allah, Foad, Abera, Semaw F., Puthenpurakal Abraham, Jerry, Abu-Rmeileh, Niveen M.E., Aburto, Tania C., Adou, Arsène K., Adsuar, José C., Agardh, Emilie E., Al Khabouri, Mazin J., Al Lami, Faris H., Albittar, Mohammed I., Alegretti, Miguel A., Aleman, Alicia V., Alemu, Zewdie A., Alfonso-Cristancho, Rafael, Ali, Mohammed K., Allen, Peter J., Alvis-Guzman, Nelson, Amankwaa, Adansi A., Amare, Azmeraw T., Ameh, Emmanuel A., Anderson, Benjamin O., Antonio, Carl Abelardo T., Argeseanu Cunningham, Solveig, Arsic Arsenijevic, Valentina S., Asghar, Rana J., Atkins, Lydia S., Avila, Marco A., Bahit, Maria C., Barber, Ryan M., Barker-Collo, Suzanne L., Barrero, Lope H., Barrientos-Gutierrez, Tonatiuh, Basto-Abreu, Ana C., Basulaiman, Mohammed O., Batis Ruvalcaba, Carolina, Bell, Michelle L., Bennett, Derrick A., Beyene, Tariku J., Bhutta, Zulfiqar A., Bin Abdulhak, Aref A., Blore, Jed D., Blyth, Fiona M., Bohensky, Megan A., Bora Başara, Berrak, Bornstein, Natan M., Bourne, Rupert R., Breitborde, Nicholas J., Briggs, Adam D.M., Broday, David M., Brooks, Peter M., Bruce, Nigel G., Brugha, Traolach S., Bui, Linh N., Bulloch, Andrew G., Burney, Peter G.J., Campos-Nonato, Ismael R., Campuzano, Julio C., Cantoral, Alejandra J., Carpenter, David O., Castañeda-Orjuela, Carlos A., Castro, Ruben E., Catalá-López, Ferrán, Chadha, Vineet K., Chang, Jung-Chen, Charlson, Fiona J., Chiang, Peggy P., Chimed-Ochir, Odgerel, Christophi, Costas A., Chuang, Ting-Wu, Chugh, Sumeet S., Claßen, Thomas K.D., Colquhoun, Samantha M., Contreras, Alejandra G., Cooper, Leslie T., Courville, Karen J., Criqui, Michael H., Cuevas-Nasu, Lucia, Damsere-Derry, Jame, Dargan, Paul I., Davitoiu, Dragos V., De Castro, E. Filipa, De La Cruz-Góngora, Vanessa, De Lima, Graça, Del Pozo-Cruz, Borja, Dellavalle, Robert P., Des Jarlais, Don C., Deveber, Gabrielle A., Devries, Karen M., Dharmaratne, Samath D., Dherani, Mukesh K., Ding, Eric L., Driscoll, Tim R., Durrani, Adnan M., Ebel, Beth E., Ellenbogen, Richard G., Elshrek, Yousef M., Ermakov, Sergey P., Erskine, Holly E., Faraon, Emerito Jose A., Fay, Derek F.J., Feigin, Valery L., Feigl, Andrea B., Fereshtehnejad, Seyed-Mohammad, Ferrari, Alize J., Ferri, Cleusa P., Flaxman, Abraham D., Fleming, Thomas D., Foreman, Kyle J., Fra Paleo, Urbano, Franklin, Richard C., Gankpé, Fortuné G., Gansevoort, Ron T., García-Guerra, Francisco A., Geleijnse, Johanna M., Gessner, Bradford D., Gibney, Katherine B., Gillum, Richard F., Ginawi, Ibrahim A.M., Gomez Dantes, Hector, Gonzalez De Cosio, Teresita, González-Castell, Dinorah, Gotay, Carolyn C., Gouda, Hebe N., Guerrant, Richard L., Gugnani, Harish C., Gutiérrez, Reyna A., Hafezi-Nejad, Nima, Halasa, Yara A., Hamadeh, Randah R., Hankey, Graeme J., Harb, Hilda L., Hay, Simon I., Hedayati, Mohammad T., Heredia-Pi, Ileana B., Heuton, Kyle R., Hoek, Hans W., Hoffman, Howard J., Hornberger, John C., Hosgood, H., Hoy, Damian G., Huang, John J., Hubbell, Bryan J., Iannarone, Marissa L., Iburg, Kim M., Idrisov, Bulat T., Jacobsen, Kathryn H., Jansen, Henrica A., Jarvis, Deborah L., Jassal, Simerjot K., Jensen, Paul N., Jonas, Jost B., Kany Roseline, Sidibe S., Karam, Nadim E., Karema, Corine K., Kazi, Dhruv S., Kemp, Andrew H., Kengne, Andre P., Khader, Yousef S., Ali Hassan Khalifa, Shams Eldin, Khan, Ejaz A., Khang, Young-Ho, Kimokoti, Ruth W., Kinge, Jonas M., Kissela, Brett M., Knibbs, Luke D., Kuate Defo, Barthelemy, Kucuk Bicer, Burcu, Kuipers, Ernst J., Kulkarni, Veena S., Kwan, Gene F., Lakshmana Balaji, Arjun, Lansingh, Van C., Larson, Heidi J., Laryea, Dennis O., Lavados, Pablo M., Lawrynowicz, Alicia E., Leasher, Janet L., Lee, Jong-Tae, Lim, Stephen S., Lipshultz, Steven E., Lloyd, Belinda K., London, Stephanie J., Lortet-Tieulent, Joannie, Lotufo, Paulo A., Machado, Vasco M.P., Macintyre, Michael F., Magis-Rodriguez, Carlo, Mahdi, Abbas A., Mapoma, Christopher C., Margolis, David J., Marks, Guy B., Martin, Randall V., Marzan, Melvin B., Mashal, Mohammad T., Mason-Jones, Amanda J., Mayosi, Bongani M., Mazorodze, Tasara T., Mckay, Abigail C., Meaney, Peter A., Mejia-Rodriguez, Fabiola, Melaku, Yohannes A., Memish, Ziad A., Mensah, George A., Apolinary Mhimbira, Franci, Miller, Ted R., Mills, Edward J., Mohamed Ibrahim, Norlinah, Mohammad, Karzan A., Mokdad, Ali H., Mola, Glen L., Montañez Hernandez, Julio C., Moore, Ami R., Moturi, Wilkister N., Mueller, Ulrich O., Mullany, Erin C., Murthy, Kinnari S., Naidoo, Kovin S., Narayan, K.M. Venkat, Neupane, Sudan P., Newton, Charles R., Ngalesoni, Frida N., Ngirabega, Jean De Dieu, Nguyen, Nhung T., Nieuwenhuijsen, Mark J., Nisar, Muhammad I., Nogueira, José R., Nolla, Joan M., Norheim, Ole F., Norman, Rosana E., Oh, In-Hwan, Olusanya, Bolajoko O., Omer, Saad B., Pagcatipunan, Rodolfo S., Pain, Amanda W., Pandian, Jeyaraj D., Panelo, Carlo Irwin A., Park, Eun-Kee, Parry, Charles D., Paternina Caicedo, Angel J., Patten, Scott B., Paul, Vinod K., Pavlin, Boris I., Pedraza, Lilia S., Pejin Stokic, Ljiljana, Pereira, David M., Perez-Padilla, Rogelio, Perez-Ruiz, Fernando, Perry, Samuel A.L., Phillips, Michael R., Polanczyk, Guilherme V., Pond, Constance D., Prasad, Noela M., Qato, Dima M., Quezada, Amado D., Quistberg, D. Alex A., Rahimi-Movaghar, Vafa, Ur Rahman, Sajjad, Rana, Saleem M., Refaat, Amany H., Ribeiro, Antonio L., Riccio, Patricia M., Rojas-Rueda, David, Ruhago, George M., Sacco, Ralph L., Salomon, Joshua A., Sampson, Uchechukwu K., Sanabria, Juan R., Sánchez-Pimienta, Tania G., Sanchez-Riera, Lidia, Santos, Itamar S., Saunders, James E., Saylan, Mete I., Schmidt, Jürgen C., Schneider, Ione J.C., Schwebel, David C., Scott, James G., Sepanlou, Sadaf G., Servan-Mori, Edson E., Shamah Levy, Teresa, Shin, Hwashin H., Sigfusdottir, Inga D., Silberberg, Donald H., Simard, Edgar P., Singh, Gitanjali M., Singh, Jasvinder A., Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stapelberg, Nicolas J.C., Stein, Dan J., Stein, Murray B., Sunguya, Bruno F., Sykes, Bryan L., Tabb, Karen M., Talongwa, Roberto T., Te Ao, Braden J., Teixeira, Carolina M., Téllez Rojo, Martha M., Terkawi, Abdullah S., Texcalac-Sangrador, José Lui, Thackway, Sarah V., Thorne-Lyman, Andrew L., Thrift, Amanda G., Thurston, George D., Towbin, Jeffrey A., Tran, Bach X., Tsala Dimbuene, Zacharie, Uchendu, Uche S., Ukwaja, Kingsley N., Uzun, Selen B., Van De Vijver, Steven, Van Gool, Coen H., Van Os, Jim, Varakin, Yuri Y., Vasankari, Tommi J., Vasconcelos, Ana Maria N., Vavilala, Monica S., Veerman, Lennert J., Velasquez-Melendez, Gustavo, Venketasubramanian, N., Violante, Francesco S., Victorovich Vlassov, Vasiliy, Wagner, Gregory R., Waller, Stephen G., Wallin, Mitchell T., Warouw, Tati S., Watts, Charlotte H., Weintraub, Robert G., Whiteford, Harvey A., Wilkinson, James D., Williams, Hywel C., Williams, Thomas N., Woldeyohannes, Solomon M., Wolfe, Charles D.A., Wong, John Q., Woolf, Anthony D., Wright, Jonathan L., Yan, Lijing L., Yentür, Gökalp K., Yoon, Seok-Jun, Younis, Mustafa Z., Zaki, Maysaa E., Zunt, Joseph R., Lopez, Alan D., and Temesgen, A.M.

Subjects
Male, Fine particulate matter, Nutrition and Disease, MESH : Sanitation, Health Behavior, Diseases, MESH: Metabolic Diseases, MESH: Global Health, 030204 cardiovascular system & hematology, MESH: Risk Assessment, Global Health, MESH : Nutritional Status, MESH: Occupational Exposure, 0302 clinical medicine, Unsafe Sex, MESH: Risk Factors, Risk Factors, Voeding en Ziekte, Medicine, Air-pollution, MESH : Female, 030212 general & internal medicine, MESH : Risk Assessment, Sanitation, Wasting, 2. Zero hunger, Factors de risc en les malalties, Medicine (all), [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, MESH : Occupational Diseases, MESH: Nutritional Status, All-cause mortality, MESH : Risk Factors, humanities, Environmental Exposure, Female, Humans, Metabolic Diseases, Nutritional Status, Occupational Diseases, Occupational Exposure, Risk Assessment, Tobacco smoking, 3. Good health, Nutritional Statu, MESH : Occupational Exposure, MESH : Metabolic Diseases, Cohort, medicine.symptom, Risk assessment, Blood-pressure, Human, MESH: Occupational Diseases, Risk factors in diseases, Coronary-heart-disease, MESH : Male, MESH: Health Behavior, MESH: Environmental Exposure, Population health, Body-mass index, 03 medical and health sciences, Household cooking, Cardiovascular-disease, Environmental health, General & Internal Medicine, parasitic diseases, Life Science, MESH: Sanitation, Risk factor, MESH : Health Behavior, VLAG, GBD2013, MESH: Humans, business.industry, Risk Factor, Global Burden of Disease Study, 79 behavioural, environmental and occupational, and metabolic risks, Long-term exposure, MESH : Humans, CAUSE-SPECIFIC MORTALITY, MESH: Male, Metabolic Disease, Occupational Disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, MALE BRITISH DOCTORS, Years of potential life lost, Relative risk, Malalties, MESH : Global Health, OUTDOOR AIR-POLLUTION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Environmental Exposure, MESH: Female
Abstract

Summary Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation. Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the fi rst of a series of annual updates of the GBD. Risk factor quantifi cation, particularly of modifi able risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the fi rst level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular fi ltration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation.

Published
2015
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41. Using formative research to promote antenatal care attendance and iron folic acid supplementation in Zinder, Niger

Author

K. Ryan Wessells, Sonja Y. Hess, Jennifer N. Nielsen, Thierno Faye, Banda Ndiaye, Nancy Keith, Césaire T. Ouédraogo, Maimouna Doudou, and Ibrahim Foungotin Bamba

Subjects
Adult, 0301 basic medicine, Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Iron+folic acid, Psychological intervention, Behaviour change communication, Health Services Accessibility, Interviews as Topic, 03 medical and health sciences, Folic Acid, 0302 clinical medicine, Pregnancy, hemic and lymphatic diseases, Humans, Medicine, Niger, 030212 general & internal medicine, Pregnancy outcomes, reproductive and urinary physiology, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Public Health, Environmental and Occupational Health, Attendance, Obstetrics and Gynecology, Prenatal Care, Original Articles, Focus Groups, medicine.disease, Focus group, female genital diseases and pregnancy complications, Family medicine, Dietary Supplements, Pediatrics, Perinatology and Child Health, Physical therapy, Patient Compliance, Female, business, Formative research
Abstract

In Niger, use of antenatal care (ANC) and iron folic acid (IFA) supplements is suboptimal. The objectives of this paper are as follows: (a) to conduct formative research to understand barriers and beliefs among pregnant women related to ANC, IFA supplementation, and pregnancy outcomes; (b) assess the quality of currently provided ANC services; (c) use the findings to guide the development of programmatic interventions to improve coverage of ANC services and IFA supplementation of pregnant women. Structured in‐home interviews (n = 72) and focus groups (n = 4) were conducted with pregnant women in 4 randomly selected villages in rural Zinder. ANC consultations (n = 33) were observed in 5 randomly selected health centres, and exit interviews were conducted with all pregnant women and seven health agents following these observations. During workshops with stakeholders, results of the formative research were interpreted, and programmatic interventions were developed. In home interviews, 72% of women reported having attended at least one ANC visit. They also reported husbands (71%), mothers (40%), and friends (33%) supporting ANC attendance. Among those having attended ANC, only 65% reported taking IFA the day prior to the interview. Three of five health centres visited had IFA in stock. Health staff did not provide IFA supplements during 18 of 33 observed ANC consultations of which only 7 cases could be explained by the lack of IFA supplements in stock. Findings were used to design a 3‐pronged intervention: (a) behaviour change communication activities in communities; (b) quality improvement activities in health centres to strengthen ANC; and (c) provision of key supplies required for ANC.

Published
2017
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42. Asymptomatic Malaria Infection Affects the Interpretation of Biomarkers of Iron and Vitamin A Status, Even after Adjusting for Systemic Inflammation, but Does Not Affect Plasma Zinc Concentrations among Young Children in Burkina Faso

Author

K. Ryan Wessells, Zinewende Ouedraogo, Noel Rouamba, Kenneth H. Brown, Jean-Bosco Ouédraogo, and Sonja Y. Hess

Subjects
Male, Medicine (miscellaneous), Hemoglobins, chemistry.chemical_compound, Prevalence, Micronutrients, Child, Vitamin A, Randomized Controlled Trials as Topic, Nutrition and Dietetics, Anemia, Iron-Deficiency, biology, Vitamin A Deficiency, Acute-phase protein, Orosomucoid, Micronutrient, Zinc, C-Reactive Protein, Female, medicine.symptom, Iron, Dietary, Vitamin, medicine.medical_specialty, Adolescent, Nutritional Status, Asymptomatic, Internal medicine, Burkina Faso, parasitic diseases, medicine, Humans, Acute-Phase Reaction, Soluble transferrin receptor, business.industry, Proteins, medicine.disease, Malaria, Retinol-Binding Proteins, Ferritin, Vitamin A deficiency, Retinol binding protein, Cross-Sectional Studies, Endocrinology, chemistry, Asymptomatic Diseases, Dietary Supplements, Ferritins, Immunology, Linear Models, biology.protein, business, Biomarkers, Acute-Phase Proteins
Abstract

BACKGROUND Biomarkers of iron [plasma ferritin (pF)], vitamin A [retinol binding protein (RBP)], and zinc status [plasma zinc (pZn)] are affected by the acute phase response, independent of micronutrient status. OBJECTIVE The objective of these analyses was to assess how asymptomatic malaria infection affects the interpretation of these biomarkers after adjustment for elevated acute phase proteins (APPs). METHODS Soluble transferrin receptor (sTfR), pF, RBP, and pZn concentrations were measured among 451 asymptomatic children aged 6-23 mo in Burkina Faso and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or α-1-acid-glycoprotein ≥1 g/L) based on a 4-group categorical model. Plasma histidine-rich protein II (HRP2) concentrations ≥0.75 μg/L were considered indicative of current or recent malaria parasitemia. RESULTS Of the children in the study, 57.4% had at least 1 elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5 ± 1.5 μg/L vs. 11.1 ± 0.8 μg/L; P < 0.001) and lower RBP (0.79 ± 0.01 μmol/L vs. 0.92 ± 0.01 μmol/L; P < 0.001) than those without, but there were no differences in pZn among those with and without elevated HRP2 (64.9 ± 12.7 μg/dL vs. 64.9 ± 11.1 μg/dL; P = 0.98). Children with elevated HRP2 had higher sTfR than those without (17.6 ± 0.5 mg/L vs. 12.3 ± 0.4 mg/L; P < 0.0001). After adjusting for HRP2, along with APP, the estimated prevalence of iron deficiency (pF < 12 μg/L) increased from 38.7% to 50.6% and vitamin A deficiency (RBP < 0.84 μmol/L) decreased from 33.4% to 27.7%. CONCLUSIONS Asymptomatic malaria is associated with indicators of micronutrient status, even after adjusting for APP. Adjusting indicators of iron and vitamin A status based only on APP may inaccurately estimate the prevalence of micronutrient deficiencies in settings with a high prevalence of malaria and inflammation. This trial was registered at clinicaltrials.gov as NCT00944853.

Published
2014
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43. Effects of Zinc Alone versus Zinc-Containing Multiple Micronutrient Powder on Insulin-Like Growth Factor 1 (IGF1) and IGF Binding Protein-3 (IGFBP3) in Laotian Children (OR07-05-19)

Author

K. Ryan Wessells, Robin Berstein, Sengchanh Kounnavong, Maxwell A. Barffour, Guy-Marino Hinnouho, Charles D Arnold, and Sonja Y. Hess

Subjects
Global Nutrition, Molar, medicine.medical_specialty, Nutrition and Dietetics, Chemistry, medicine.medical_treatment, IGFBP3, Medicine (miscellaneous), chemistry.chemical_element, Zinc, Micronutrient, Insulin-like growth factor, Endocrinology, Internal medicine, medicine, Binding protein 3, Underweight, medicine.symptom, Food Science, Biological availability
Abstract

OBJECTIVES: To assess a) the impact of daily preventive zinc tablets (7 mg; PZ), multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP) or placebo on Insulin-like Growth Factor 1 (IGF1), IGF Binding Protein 3 (IGFBP3) and IGF1 bioavailability (indexed by molar IGF1: IGFBP3 ratio), among Laotian children aged 6–23 mo; b) potential effect modification by baseline physical growth status. METHODS: Plasma samples from 419 children participating in the parent trial (n = 3407) were collected at baseline and after ∼9 mo (endline). Determination of IGF1 and IGFBP3 were done via an automated chemiluminescent assay. Linear regression models were used to assess main and modifying effects of PZ and MNP on IGF1 and IGFBP3, controlling for age, sex, district and baseline values of each biomarker. RESULTS: The parent trial found no overall treatment effects on physical growth. In this subgroup, mean age at baseline was 14.2 ± 5.1 mo and ∼38% were stunted. IGF1 and IGFBP3 at baseline were 45.9 ng/ml and 2143.0 ng/ml, respectively. At endline, geometric mean IGF1 (∼39.0–39.2 ng/ml; P = 0.99), IGFBP3 (2038–2076 ng/ml; P = 0.83) and molar IGF1: IGFBP3 ratio (0.071–0.073; P = 0.74) did not differ by group. Baseline weight-for-age z-score (WAZ) modified the treatment effect on IGFBP3 (p for interaction = 0.05) and molar IGF1: IGFBP3 (p for interaction = 0.04). In non-underweight children (WAZ ≥ -2), mean IGFBP3 in the PZ group (2000 ng/ml) was significantly lower than in the placebo (2148 ng/ml; P = 0.03) and MNP (2157 ng/ml; P = 0.03) groups. In underweight children, however, the IGFBP3 in the PZ group (2039 ng/ml) was higher than the placebo (1774 ng/ml; P = 0.05) but not the MNP (1881 ng/ml; P = 0.15) group. PZ (relative to placebo and MNP) appeared to reduce the bioavailability of IGF1 in underweight children, while increasing IGF1 bioavailability in non-underweight children (p interaction = 0.04). CONCLUSIONS: IGF1 in this population did not respond to PZ or MNP. PZ (relative to placebo and MNP) was associated with higher endline IGFBP3 concentrations in underweight children but lower values in non-underweight children. These results suggest that PZ affected activity in the GH-IGF axis in these children, but additional evidence is needed to understand long term implications for growth in this population. FUNDING SOURCES: By The Thrasher Research Fund, with support from the Mathile Institute for the Advancement of Human Nutrition, Nutrition International and the Bill & Melinda Gates Foundation.

Published
2019
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44. Effects of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction Among Young Laotian Children (P04-012-19)

Author

Somphou Sayasone, Sengchanh Kounnavong, Maxwell A. Barffour, Kenneth H. Brown, Guy-Marino Hinnouho, Charles D Arnold, Sonja Y. Hess, and K. Ryan Wessells

Subjects
Nutrition and Dietetics, chemistry, business.industry, Medicine (miscellaneous), Medicine, Physiology, chemistry.chemical_element, Zinc, business, Feces, Community and Public Health Nutrition, Food Science
Abstract

OBJECTIVES: To assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO) and calprotectin (CAL) among young Laotian children and explore modifying effects of MPO, CAL and NEO on growth METHODS: In a double-blind controlled trial, children 6–23 mo of age were randomized to receive either daily preventive zinc tablets (PZ; 7 mg/d), daily micronutrient powder sachets (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc supplements for diarrhea treatment (TZ; 20 mg/d for 10 days) or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO and CAL were determined in a randomly selected sub-sample of 720 children using commercially available ELISA kits. Linear regression models were used to assess main and modifying effects while controlling for baseline value, age and district RESULTS: The baseline prevalence of stunting was 39.3%, and there was no overall treatment effect on physical growth in the parent trial. At endline, geometric mean fecal MPO, NEO and CAL concentrations did not differ among the 4 groups (all P > 0.23). There was an effect modification by baseline concentrations of NEO and CAL on endline stunting (p for interaction = 0.01 and 0.02, respectively). Among children in the lowest quintile of NEO concentrations, there was a trend towards a higher stunting prevalence at endline in the TZ [47.1% (35.6, 58.7)] and the MNP [45.3% (32.7, 57.9)] groups compared to the PZ [33.6% (21.0, 46.3)] and the control [33.9% (22.8, 44.9)] groups. Similar results were found among children in the lowest quintile of CAL concentrations. Moreover, baseline concentration of CAL, modified the impact of the interventions on weight-for-height z-scores (WHZ) (p for interaction = 0.074). Among children in the lowest quintile of CAL concentrations, there was a trend towards a higher WHZ at endline in the MNP [−0.57 (−0.73, −0.42)] and TZ [−0.68 (−0.86, −0.51)] groups compared to the control [−0.79 (−0.97, −0.61)] and the PZ [−0.88 (−1.05, −0.72)] groups. CONCLUSIONS: In this population of young Laotian children PZ, MNP and TZ had no overall impact on EED or growth, but intestinal function modified the growth response to supplementation suggesting its potential role in the pathways of growth impairment. FUNDING SOURCES: Funded by the Bill & Melinda Gates Foundation, Nutrition International and the Mathile Institute for the Advancement of Human Nutrition.

Published
2019
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45. Micronutrient Status among Pregnant Women in Zinder, Niger and Risk Factors Associated with Deficiency

Author

M. Thierno Faye, Sonja Y. Hess, Rebecca R Young, Alex Brito, K. Ryan Wessells, and Césaire T. Ouédraogo

Subjects
0301 basic medicine, Rural Population, Pediatrics, Reproductive health and childbirth, 0302 clinical medicine, iron, Pregnancy, Risk Factors, Medicine, 030212 general & internal medicine, Micronutrients, Niger, education.field_of_study, Nutrition and Dietetics, biology, Obstetrics, zinc, Pregnancy Outcome, vitamin, Iron deficiency, Hematology, deficiency, Micronutrient, anemia, Female, lcsh:Nutrition. Foods and food supply, Adult, medicine.medical_specialty, Anemia, Population, micronutrient, pregnancy, antenatal care, Nutritional Status, lcsh:TX341-641, Article, 03 medical and health sciences, Food Sciences, Clinical Research, Humans, Vitamin B12, education, Soluble transferrin receptor, Nutrition, 030109 nutrition & dietetics, business.industry, Prevention, Maternal Nutritional Physiological Phenomena, medicine.disease, Ferritin, Good Health and Well Being, biology.protein, business, Food Science
Abstract

Anemia and micronutrient (MN) deficiencies in pregnant women are associated with adverse pregnancy outcomes. In Niger, 58.6% of pregnant women are anemic; however, MN statuses are unknown. The study objectives were to estimate the prevalence of MN deficiencies among pregnant women in Zinder, Niger and explore associated risk factors. Pregnant women living in randomly selected rural villages (n = 88) were included. Capillary and venous blood samples (n = 770) were analyzed for hemoglobin (Hb) and plasma ferritin, soluble transferrin receptor (sTfR), zinc (pZn), retinol binding protein (RBP), folate and vitamin B12. C-reactive protein and alpha-1-acid glycoprotein were measured to adjust for inflammation. The prevalence of MN deficiencies in pregnant woman was high, indicative of a severe public health problem. Prevalence of iron deficiency was 20.7% and 35.7%, by ferritin (8.3 mg/L), respectively. In total, 40.7% of women had low pZn (

Published
2017

46. Plasma Zinc Concentration Responds Rapidly to the Initiation and Discontinuation of Short-Term Zinc Supplementation in Healthy Men1–4

Author

Sonja Y. Hess, Kenneth H. Brown, Leslie R. Woodhouse, Joshua M. Jorgensen, Janet M Peerson, and K. Ryan Wessells

Subjects
medicine.medical_specialty, Nutrition and Dietetics, Dose, Medicine (miscellaneous), chemistry.chemical_element, Zinc, Micronutrient, Placebo, Discontinuation, law.invention, Endocrinology, chemistry, Randomized controlled trial, Blood chemistry, law, Internal medicine, Blood plasma, medicine
Abstract

To assist with the evaluation of zinc (Zn) intervention programs, information is needed on the magnitude and velocity of response of plasma Zn concentration following changes in Zn intake. Our objective in this study was to measure plasma Zn concentration of healthy adult men before and after initiation and discontinuation of 1 of 2 dosages of Zn supplements or placebo. We conducted a randomized, double-blind, placebo-controlled trial in 58 apparently healthy males aged 19-54 y. Participants received 1 of 3 liquid supplements daily for 21 d: 10 or 20 mg Zn/d, as Zn sulfate, or placebo. Fasting plasma Zn concentrations were measured on 14 occasions before, during, and after supplementation. Data were analyzed using mixed-model ANCOVA. The plasma Zn concentration was related to day of study (P < 0.0001) and study group (P < 0.0001). Controlling for baseline concentrations, plasma Zn concentrations were consistently elevated above baseline by d 5 among individuals in both of the Zn-supplemented groups compared with those receiving placebo supplements, regardless of their initial plasma Zn concentration. There were no significant group-wise differences between those who received either 10 or 20 mg/d Zn. Plasma Zn concentrations of supplemented individuals declined following withdrawal of supplementation and within 2 wk no longer differed from those of the placebo group. Change in the plasma Zn concentration is a useful indicator to monitor compliance with, and possibly effectiveness of, Zn supplementation programs. To ensure accurate interpretation of the results, samples should be collected while the intervention is still in progress.

Published
2010
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47. Prevalence of and factors associated with antenatal care seeking and adherence to recommended iron-folic acid supplementation among pregnant women in Zinder, Niger

Author

Rebecca R Young, Sonja Y. Hess, Césaire T. Ouédraogo, Sara E. Wuehler, K. Ryan Wessells, Khadija Begum, and M. Thierno Faye

Subjects
0301 basic medicine, Care seeking, Health Behavior, Psychological intervention, Supplement Articles, 0302 clinical medicine, Pregnancy, hemic and lymphatic diseases, Niger, 030212 general & internal medicine, reproductive and urinary physiology, Nutrition and Dietetics, Anemia, Iron-Deficiency, Obstetrics, Attendance, Obstetrics and Gynecology, Gestational age, Prenatal Care, Middle Aged, female genital diseases and pregnancy complications, Educational Status, Female, Iron, Dietary, Adult, medicine.medical_specialty, Adolescent, Iron+folic acid, Nutritional Status, Gestational Age, World Health Organization, Young Adult, 03 medical and health sciences, Folic Acid, parasitic diseases, medicine, Animals, Humans, Spouses, 030109 nutrition & dietetics, business.industry, Public Health, Environmental and Occupational Health, Odds ratio, bacterial infections and mycoses, medicine.disease, Confidence interval, Social Class, Dietary Supplements, Pediatrics, Perinatology and Child Health, Patient Compliance, business
Abstract

The World Health Organization recommends iron and folic acid (IFA) supplementation for pregnant women. The high prevalence of anaemia among pregnant women in Niger warrants better understanding of the utilization of antenatal care (ANC) and IFA. We aimed to assess the prevalence of and factors associated with ANC coverage and adherence to IFA recommendation among pregnant women. Pregnant women (n = 923) from 64 randomly selected villages within the catchment area of 12 health centres were interviewed during a baseline household survey in Zinder, Niger. ANC and IFA coverage were 60.1% and 43.6%, respectively. Only 71.7% of women who attended ANC received IFA. Of the 401 women who reportedly received any IFA supplements, 99.3% had attended any ANC during their current pregnancy and 68.6% reported adherence to recommended IFA supplementation (i.e., consumed IFA every day in the previous week). Women with gestational age ≥27 weeks were more likely to have attended ANC than women with gestational age

Published
2018
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48. Development of a plasma zinc concentration cutoff to identify individuals with severe zinc deficiency based on results from adults undergoing experimental severe dietary zinc restriction and individuals with acrodermatitis enteropathica

Author

Janet C. King, K. Ryan Wessells, and Kenneth H. Brown

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Medicine (miscellaneous), chemistry.chemical_element, Zinc, Asymptomatic, Gastroenterology, Sensitivity and Specificity, Young Adult, Internal medicine, medicine, Humans, Point of zero charge, Longitudinal Studies, Young adult, Nutrition and Dietetics, business.industry, Acrodermatitis enteropathica, Acrodermatitis, medicine.disease, Diarrhea, Cross-Sectional Studies, chemistry, Area Under Curve, Zinc deficiency, Biomarker (medicine), Female, medicine.symptom, business, Biomarkers
Abstract

Plasma zinc concentration (PZC) is a recommended biomarker to assess zinc status and the risk of zinc deficiency in populations. However, the relation between PZC and clinical signs of zinc deficiency remains uncertain. These analyses were conducted to evaluate the relation between PZC and clinical signs of zinc deficiency and to determine a cutoff for PZC below which individuals would have an increased likelihood of having clinical signs associated with zinc deficiency. Electronic bibliographic searches were conducted of literature indexed in PubMed, Embase, CINAHL Plus, and EBSCO and related to experimental zinc depletion studies in adults and case reports in children and adults (ages

Published
2014

49. Relationship between plasma zinc concentrations and clinical signs of zinc deficiency (1043.9)

Author

Janet C. King, K. Ryan Wessells, and Kenneth H. Brown

Subjects
medicine.medical_specialty, business.industry, Acrodermatitis enteropathica, chemistry.chemical_element, Zinc, medicine.disease, Biochemistry, Dietary zinc, Endocrinology, chemistry, Internal medicine, Genetics, medicine, Zinc deficiency, Point of zero charge, business, Molecular Biology, Plasma zinc, Biotechnology
Abstract

Plasma zinc concentration (PZC) is a recommended biomarker to assess zinc (Zn) status and the risk of Zn deficiency in populations. However, the relationship between PZC and clinical signs of Zn deficiency remains uncertain. Thus, we analyzed available data from dietary Zn restriction studies and case reports of acrodermatitis enteropathica (AE) to determine a PZC cutoff below which individuals would have an increased likelihood of having clinical signs associated with Zn deficiency. In studies of dietary zinc restriction (

Published
2014
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50. Associations between intestinal mucosal function and changes in plasma zinc concentration following zinc supplementation

Author

Christopher Duggan, K. Ryan Wessells, Zinewende Ouedraogo, Mark D. Kellogg, Jean-Bosco Ouédraogo, Sonja Y. Hess, Rie Goto, Kenneth H. Brown, and Noel Rouamba

Subjects
Adult, Male, medicine.medical_specialty, Malabsorption, Adolescent, chemistry.chemical_element, Zinc, Intestinal absorption, Permeability, Article, Lactulose, Young Adult, Intestinal mucosa, Malabsorption Syndromes, Reference Values, Internal medicine, Burkina Faso, medicine, Humans, Mineral absorption, Mannitol, Intestinal Mucosa, Child, Environmental enteropathy, business.industry, Gastroenterology, medicine.disease, Zinc Sulfate, Endocrinology, chemistry, Intestinal Absorption, Pediatrics, Perinatology and Child Health, Dietary Supplements, Citrulline, Female, business, medicine.drug
Abstract

Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12, and folate; however, little information is available on mineral absorption. We therefore investigated the relation between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc (Zn) absorption, as estimated by the change in plasma Zn concentration (PZC) following short-term Zn or placebo supplementation.We conducted a randomized, partially masked, placebo-controlled trial among 282 apparently healthy children 6 to 23 months of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg Zn, as zinc sulfate, or placebo, daily for 21 days.At baseline, mean ± standard deviation PZC was 62.9 ± 11.9 μg/dL; median (interquartile range) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentrations were 0.04 (0.03-0.07) and 11.4 (9.0-15.6) μmol/L, respectively. Change in PZC was significantly greater in the Zn-supplemented versus placebo group (15.6 ± 13.3 vs 0.02 ± 10.9 μg/dL; P0.0001), and was negatively associated with initial urinary L:M recovery ratio (-1.1 μg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relation did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC.Although altered intestinal permeability may reduce dietary Zn absorption, it likely does not undermine the efficacy of Zn supplementation, given the large increases in PZC following short-term Zn supplementation observed in this study, even among those with increased urinary L:M recovery ratios.

Published
2013

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