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      Enteric dysfunction and other factors associated with attained size at 5 years: MAL-ED birth cohort study findings

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          ABSTRACT

          Background

          Poor growth in early childhood has been associated with increased risk of mortality and morbidity, as well as long-term deficits in cognitive development and economic productivity.

          Objectives

          Data from the MAL-ED cohort study were used to identify factors in the first 2 y of life that are associated with height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, BMIZ) at 5 y of age.

          Methods

          A total of 1017 children were followed from near birth until 5 y of age at sites in Bangladesh, Brazil, India, Nepal, Peru, South Africa, and Tanzania. Data were collected on their growth, environmental enteric dysfunction (EED), micronutrient status, enteric pathogen burden, illness prevalence, dietary intake, and various other socio-economic and environmental factors.

          Results

          EED biomarkers were related to size at 5 y. Mean lactulose:mannitol z-scores during the first 2 y of life were negatively associated with all of the growth measures (HAZ: −0.11 [95% CI: −0.19, −0.03]; WAZ: −0.16 [95% CI: −0.26, −0.06]; BMIZ: −0.11 [95% CI: −0.23, 0.0]). Myeloperoxidase was negatively associated with weight (WAZ: −0.52 [95% CI: −0.78, −0.26] and BMIZ: −0.56 [95% CI: −0.86, −0.26]); whereas α-1-antitrypsin had a negative association with HAZ (−0.28 [95% CI: −0.52, −0.04]). Transferrin receptor was positively related to HAZ (0.18 [95% CI: 0.06, 0.30]) and WAZ (0.21 [95% CI: 0.07, 0.35]). Hemoglobin was positively related to HAZ (0.06 [95% CI: 0.00, 0.12]), and ferritin was negatively related to HAZ (−0.08 [95% CI: −0.12, −0.04]). Bacterial density in stool was negatively associated with HAZ (−0.04 [95% CI: −0.08, 0.00]), but illness symptoms did not have any effect on size at 5 y.

          Conclusions

          EED markers, bacterial density, and iron markers are associated with growth at 5 y of age. Interventions to reduce bacterial burden and EED may improve long-term growth in low-income settings.

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          Most cited references24

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          Effects of perinatal mental disorders on the fetus and child.

          Perinatal mental disorders are associated with increased risk of psychological and developmental disturbances in children. However, these disturbances are not inevitable. In this Series paper, we summarise evidence for associations between parental disorders and offspring outcomes from fetal development to adolescence in high-income, middle-income, and low-income countries. We assess evidence for mechanisms underlying transmission of disturbance, the role of mediating variables (underlying links between parent psychopathology and offspring outcomes) and possible moderators (which change the strength of any association), and focus on factors that are potentially modifiable, including parenting quality, social (including partner) and material support, and duration of the parental disorder. We review research of interventions, which are mostly about maternal depression, and emphasise the need to both treat the parent's disorder and help with associated caregiving difficulties. We conclude with policy implications and underline the need for early identification of those parents at high risk and for more early interventions and prevention research, especially in socioeconomically disadvantaged populations and low-income countries.
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            Long-term consequences of stunting in early life.

            This review summarizes the impact of stunting, highlights recent research findings, discusses policy and programme implications and identifies research priorities. There is growing evidence of the connections between slow growth in height early in life and impaired health and educational and economic performance later in life. Recent research findings, including follow-up of an intervention trial in Guatemala, indicate that stunting can have long-term effects on cognitive development, school achievement, economic productivity in adulthood and maternal reproductive outcomes. This evidence has contributed to the growing scientific consensus that tackling childhood stunting is a high priority for reducing the global burden of disease and for fostering economic development. Follow-up of randomized intervention trials is needed in other regions to add to the findings of the Guatemala trial. Further research is also needed to: understand the pathways by which prevention of stunting can have long-term effects; identify the pathways through which the non-genetic transmission of nutritional effects is mediated in future generations; and determine the impact of interventions focused on linear growth in early life on chronic disease risk in adulthood. © 2011 Blackwell Publishing Ltd.
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              Serum ferritin: Past, present and future.

              Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. Copyright 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Am J Clin Nutr
                Am. J. Clin. Nutr
                ajcn
                The American Journal of Clinical Nutrition
                Oxford University Press
                0002-9165
                1938-3207
                July 2019
                25 May 2019
                25 May 2019
                : 110
                : 1
                : 131-138
                Affiliations
                [1 ]Fogarty International Center/NIH, Bethesda, MD
                [2 ]The Pennsylvania State University, University Park, PA
                [3 ]The Johns Hopkins University, Baltimore, MD
                [4 ]International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
                [5 ]University of Virginia, School of Medicine, Charlottesville, VA
                [6 ]Christian Medical College, Division of Gastrointestinal Sciences, Vellore, Tamil Nadu, India
                [7 ]Haydom Lutheran Hospital, Haydom, Manyara, Tanzania
                [8 ]Universidade Federal do Ceará, INCT—Instituto de Biomedicina do Semiárido Brasileiro, Fortaleza, Brazil
                [9 ]Walter Reed Armed Forces Research Institute of Medical Sciences (AFRIMS) Research Unit (WARUN), Kathmandu, Nepal
                [10 ]Institute of Medicine, Tribhuvan University, Kathmandu, Nepal
                [11 ]Aga Khan University, Centre of Excellence in Women and Child Health, Karachi, Pakistan
                [12 ]University of Venda, Thohoyandou, South Africa
                Author notes
                Address correspondence to LEC (e-mail: lcaulfie@ 123456jhsph.edu )
                Present address for GOL: University of Michigan, Ann Arbor, MI
                Present address for ZB: University of Toronto, Toronto, Canada
                Present address for RKC: Kathmandu Medical College, Kathmandu, Nepal
                Author information
                http://orcid.org/0000-0002-5836-9471
                http://orcid.org/0000-0002-7889-3852
                http://orcid.org/0000-0003-4437-9115
                http://orcid.org/0000-0002-4090-785X
                http://orcid.org/0000-0002-4942-3747
                http://orcid.org/0000-0002-3656-564X
                http://orcid.org/0000-0002-0299-1747
                http://orcid.org/0000-0001-7152-1004
                Article
                nqz004
                10.1093/ajcn/nqz004
                6599740
                31127812
                fd393406-7323-44da-bac3-34c697f4c166
                Copyright © American Society for Nutrition 2019.

                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
                : 20 August 2018
                : 07 January 2019
                Page count
                Pages: 8
                Funding
                Funded by: Bill & Melinda Gates Foundation 10.13039/100000865
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: D43-TW009359
                Funded by: Fogarty International Center 10.13039/100000061
                Categories
                Original Research Communications
                Growth, Development, and Pediatrics

                Nutrition & Dietetics
                growth,enteric dysfunction,iron,inflammation,permeability
                Nutrition & Dietetics
                growth, enteric dysfunction, iron, inflammation, permeability

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