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      Biomarkers of environmental enteric dysfunction are not consistently associated with linear growth velocity in rural Zimbabwean infants

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          ABSTRACT

          Background

          Child stunting remains a poorly understood, prevalent public health problem. Environmental enteric dysfunction (EED) is hypothesized to be an important underlying cause.

          Objectives

          Within a subgroup of 1169 children enrolled in the SHINE (Sanitation Hygiene Infant Nutrition Efficacy) trial in rural Zimbabwe, followed longitudinally from birth to 18 mo of age, we evaluated associations between the concentration of 11 EED biomarkers and linear growth velocity.

          Methods

          At infant ages 1, 3, 6, 12, and 18 mo, nurses measured child length and collected stool and blood; the lactulose-mannitol urine test was also conducted at all visits except at 1 mo. Stool neopterin, α-1 antitrypsin, myeloperoxidase, and regenerating gene 1β protein; urinary lactulose and mannitol; and plasma kynurenine, tryptophan, C-reactive protein, insulin-like growth factor-1 (IGF-1), soluble CD14, intestinal fatty acid binding protein, and citrulline were measured. We analyzed the change in relative [∆ length-for-age z score (LAZ)/mo] and absolute (∆ length/mo) growth velocity during 4 age intervals (1–3 mo; 3–6 mo; 6–12 mo; and 12–18 mo) per SD increase in biomarker concentration at the start of each age interval.

          Results

          In fully adjusted models, we observed only 3 small, statistically significant associations: kynurenine:tryptophan ratio at 12 mo was associated with decreased mean LAZ velocity during the 12–18 mo interval (−0.015 LAZ/mo; 95% CI: −0.029, −0.001 LAZ/mo); mannitol excretion at 6 mo was associated with increased LAZ velocity during the 6–12 mo interval (0.013 LAZ/mo; 95% CI: 0.001, 0.025 LAZ/mo), and plasma IGF-1 at 1 mo was associated with increased LAZ velocity during the 1–3 mo interval (0.118 LAZ/mo; 95% CI: 0.024, 0.211 LAZ/mo). Results for absolute growth velocity were similar, except IGF-1 was also associated with growth during the 12–18 mo interval. We found no other associations between any EED biomarker and linear growth velocity.

          Conclusions

          None of 11 biomarkers of EED were consistently associated with linear growth among Zimbabwean children.

          This trial was registered at clinicaltrials.gov as NCT01824940.

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          Most cited references90

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          Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost?

          The Lancet, 382(9890), 452-477
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            Maternal and child undernutrition: consequences for adult health and human capital

            Summary In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and—for women—lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain—especially after infancy—is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.
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              Anthropometric reference data for international use: recommendations from a World Health Organization Expert Committee.

              The World Health Organization (WHO) convened an Expert Committee to reevaluate the use of anthropometry at different ages for assessing health, nutrition, and social wellbeing. The Committee's task included identifying reference data for anthropometric indexes when appropriate, and providing guidelines on how the data should be used. For fetal growth, the Committee recommended an existing sex-specific multiracial reference. In view of the significant technical drawbacks of the current National Center for Health Statistics (NCHS)/WHO reference and its inadequacy for assessing the growth of breast-fed infants, the Committee recommended the development of a new reference concerning weight and length/height for infants and children, which will be a complex and costly undertaking. Proper interpretation of midupper arm circumference for preschoolers requires age-specific reference data. To evaluate adolescent height-for-age, the Committee recommended the current NCHS/WHO reference. Use of the NCHS body mass index (BMI) data, with their upper percentile elevations and skewness, is undesirable for setting health goals; however, these data were provisionally recommended for defining obesity based on a combination of elevated BMI and high subcutaneous fat. The NCHS values were provisionally recommended as reference data for subscapular and triceps skinfold thicknesses. Guidelines were also provided for adjusting adolescent anthropometric comparisons for maturational status. Currently, there is no need for adult reference data for BMI; interpretation should be based on pragmatic BMI cutoffs. Finally, the Committee noted that few normative anthropometric data exist for the elderly, especially for those > 80 y of age. Proper definitions of health status, function, and biologic age remain to be developed for this group.
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                Author and article information

                Contributors
                Journal
                Am J Clin Nutr
                Am J Clin Nutr
                ajcn
                The American Journal of Clinical Nutrition
                Oxford University Press
                0002-9165
                1938-3207
                May 2021
                19 March 2021
                19 March 2021
                : 113
                : 5
                : 1185-1198
                Affiliations
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Global Alliance for Improved Nutrition , Washington, DC, USA
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo , Buffalo, NY, USA
                Department of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA
                Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Faculty of Medicine, Imperial College London , London, United Kingdom
                School of Human Development and Health, Faculty of Medicine, University of Southampton , Southampton, United Kingdom
                Program in International Nutrition, Division of Nutritional Sciences, Cornell University , Ithaca, NY, USA
                Department of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Department of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA
                Department of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA
                Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                Blizard Institute, Queen Mary University of London , London, United Kingdom
                Author notes
                Address correspondence to JHH (e-mail: jhumphr2@ 123456jhu.edu ).
                Present address for MNNM: Global Alliance for Improved Nutrition, 1701 Rhode Island Ave NW, Washington, DC 20036, USA.

                KM and RN contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-1230-2367
                Article
                nqaa416
                10.1093/ajcn/nqaa416
                8106752
                33740052
                5f90c7ca-fe0a-42b8-abcc-e9346161a9c8
                © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

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

                History
                : 05 August 2020
                : 10 December 2020
                Page count
                Pages: 14
                Funding
                Funded by: Bill & Melinda Gates Foundation, DOI 10.13039/100000865;
                Award ID: OPP1021542
                Funded by: Johns Hopkins Bloomberg School of Public Health, DOI 10.13039/100008309;
                Award ID: OPP1143707
                Funded by: Zvitambo Institute for Maternal and Child Health Research;
                Funded by: Department for International Development, UK, DOI 10.13039/501100000278;
                Funded by: Wellcome Trust, DOI 10.13039/100010269;
                Award ID: 093768/Z/10/Z
                Award ID: 108065/Z/15/Z
                Funded by: Swiss Agency for Development and Cooperation, DOI 10.13039/100009131;
                Award ID: 8106727
                Funded by: UNICEF, DOI 10.13039/100006641;
                Award ID: PCA–2017–0002
                Categories
                Original Research Communications
                AcademicSubjects/MED00060
                AcademicSubjects/MED00160

                Nutrition & Dietetics
                environmental enteric dysfunction,biomarkers,child growth,stunting,zimbabwe
                Nutrition & Dietetics
                environmental enteric dysfunction, biomarkers, child growth, stunting, zimbabwe

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