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      Association of Fish Consumption and Mercury Exposure During Pregnancy With Metabolic Health and Inflammatory Biomarkers in Children

      research-article
      , PhD 1 , 2 , , PhD 1 , , PhD 3 , 4 , , PhD 3 , 4 , , MPH 5 , , PhD 6 , , PhD 7 , , PhD 3 , 8 , 9 , , PhD 3 , 8 , 9 , , PhD 3 , 8 , 9 , , PhD 1 , , MD, PhD 3 , 8 , 9 , , PhD 3 , 8 , 9 , , MD 10 , , PhD 11 , , PhD 3 , 8 , 9 , , PhD 12 , , PhD 13 , , PhD 3 , 8 , 9 , , PhD 5 , , PhD 12 , , MD 12 , , MD, PhD 1 , , PhD 6 , , PhD 6 , , PhD 3 , 8 , 9 , , MD, PhD 1 , 2 ,
      JAMA Network Open
      American Medical Association

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          Key Points

          Question

          Is fish consumption during pregnancy associated with benefits for the metabolic health of children?

          Findings

          In this cohort study of 805 mothers and their singleton offspring, moderate fish consumption during pregnancy was associated with the downregulation of inflammation and improvements in the metabolic profile of children; high mercury exposure during pregnancy had the opposite associations.

          Meaning

          The results of this study suggest that fish consumption consistent with current recommendations during pregnancy was associated with improvements in the metabolic health of children.

          Abstract

          Importance

          The balance of mercury risk and nutritional benefit from fish intake during pregnancy for the metabolic health of offspring to date is unknown.

          Objective

          To assess the associations of fish intake and mercury exposure during pregnancy with metabolic syndrome in children and alterations in biomarkers of inflammation in children.

          Design, Setting, and Participants

          This population-based prospective birth cohort study used data from studies performed in 5 European countries (France, Greece, Norway, Spain, and the UK) between April 1, 2003, and February 26, 2016, as part of the Human Early Life Exposome (HELIX) project. Mothers and their singleton offspring were followed up until the children were aged 6 to 12 years. Data were analyzed between March 1 and August 2, 2019.

          Exposures

          Maternal fish intake during pregnancy (measured in times per week) was assessed using validated food frequency questionnaires, and maternal mercury concentration (measured in micrograms per liter) was assessed using maternal whole blood and cord blood samples.

          Main Outcomes and Measures

          An aggregate metabolic syndrome score for children was calculated using the z scores of waist circumference, systolic and diastolic blood pressures, and levels of triglyceride, high-density lipoprotein cholesterol, and insulin. A higher metabolic syndrome score (score range, −4.9 to 7.5) indicated a poorer metabolic profile. Three protein panels were used to measure several cytokines and adipokines in the plasma of children.

          Results

          The study included 805 mothers and their singleton children. Among mothers, the mean (SD) age at cohort inclusion or delivery of their infant was 31.3 (4.6) years. A total of 400 women (49.7%) had a high educational level, and 432 women (53.7%) were multiparous. Among children, the mean (SD) age was 8.4 (1.5) years (age range, 6-12 years). A total of 453 children (56.3%) were boys, and 734 children (91.2%) were of white race/ethnicity. Fish intake consistent with health recommendations (1 to 3 times per week) during pregnancy was associated with a 1-U decrease in metabolic syndrome score in children (β = −0.96; 95% CI, −1.49 to −0.42) compared with low fish consumption (<1 time per week) after adjusting for maternal mercury levels and other covariates. No further benefit was observed with fish intake of more than 3 times per week. A higher maternal mercury concentration was independently associated with an increase in the metabolic syndrome score of their offspring (β per 2-fold increase in mercury concentration = 0.18; 95% CI, 0.01-0.34). Compared with low fish intake, moderate and high fish intake during pregnancy were associated with reduced levels of proinflammatory cytokines and adipokines in children. An integrated analysis identified a cluster of children with increased susceptibility to metabolic disease, which was characterized by low fish consumption during pregnancy, high maternal mercury levels, decreased levels of adiponectin in children, and increased levels of leptin, tumor necrosis factor α, and the cytokines interleukin 6 and interleukin 1β in children.

          Conclusions and Relevance

          Results of this study suggest that moderate fish intake consistent with current health recommendations during pregnancy was associated with improvements in the metabolic health of children, while high maternal mercury exposure was associated with an unfavorable metabolic profile in children.

          Abstract

          This cohort study used data from the Human Early Life Exposome (HELIX) project, a collaboration of 5 European birth cohort studies, to examine the associations of maternal fish consumption and mercury exposure during pregnancy with metabolic health and inflammatory biomarkers in children.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation.

          Omega-3 fatty acids (ω-3 FAs) have potential anti-inflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with ω-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein β-arrestin-2 were shown to be involved in inflammasome inhibition induced by ω-3 FAs. Importantly, ω-3 FAs also prevented NLRP3 inflammasome-dependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which ω-3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of ω-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases. Copyright © 2013 Elsevier Inc. All rights reserved.
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            • Record: found
            • Abstract: not found
            • Article: not found

            Scientific Opinion on the risk for public health related to the presence of mercury and methylmercury in food

            (2012)
              Bookmark
              • Record: found
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              • Article: not found

              The Metabolic Syndrome in Children and Adolescents: Shifting the Focus to Cardiometabolic Risk Factor Clustering.

              Metabolic syndrome (MetS) was developed by the National Cholesterol Education Program Adult Treatment Panel III, identifying adults with at least 3 of 5 cardiometabolic risk factors (hyperglycemia, increased central adiposity, elevated triglycerides, decreased high-density lipoprotein cholesterol, and elevated blood pressure) who are at increased risk of diabetes and cardiovascular disease. The constellation of MetS component risk factors has a shared pathophysiology and many common treatment approaches grounded in lifestyle modification. Several attempts have been made to define MetS in the pediatric population. However, in children, the construct is difficult to define and has unclear implications for clinical care. In this Clinical Report, we focus on the importance of screening for and treating the individual risk factor components of MetS. Focusing attention on children with cardiometabolic risk factor clustering is emphasized over the need to define a pediatric MetS.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                16 March 2020
                March 2020
                16 March 2020
                : 3
                : 3
                : e201007
                Affiliations
                [1 ]Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles
                [2 ]Department of Complex Genetics and Epidemiology, CAPHRI School for Public Health and Primary Care, University of Maastricht, Maastricht, the Netherlands
                [3 ]Universitat Pompeu Fabra, Barcelona, Spain
                [4 ]Proteomics Unit, Centre de Regulacio Genomica, Barcelona Institute of Science and Technology, Barcelona, Spain
                [5 ]Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece
                [6 ]Department of Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
                [7 ]Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Inserm, CNRS, University Grenoble Alpes, Institute for Advanced Biosciences, U1209 Joint Research Center, La Tronche, Grenoble, France
                [8 ]Institute for Global Health, Barcelona, Spain
                [9 ]Consorcio de Investigacion Biomedica en Red de Epidemiologia y Salud Publica, Madrid, Spain
                [10 ]Department of Environmental Sciences, Vytautas Magnus University, Kaunas, Lithuania
                [11 ]Centre of Research in Epidemiology and Statistics, Inserm, Institut National de la Recherche Agronomique, Universite de Paris, Paris, France
                [12 ]Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
                [13 ]Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology, Heraklion, Greece
                Author notes
                Article Information
                Accepted for Publication: January 27, 2020.
                Published: March 16, 2020. doi:10.1001/jamanetworkopen.2020.1007
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Stratakis N et al. JAMA Network Open.
                Corresponding Author: Leda Chatzi, MD, PhD, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 2001 N Soto St, Los Angeles, CA 90089-9239 ( chatzi@ 123456usc.edu ).
                Author Contributions: Drs Stratakis and Chatzi had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Stratakis, Agier, Farzan, McEachan, Vafeiadi, Wright, Brantsaeter, Meltzer, Vrijheid, Chatzi.
                Acquisition, analysis, or interpretation of data: Stratakis, Conti, Borras, Sabido, Roumeliotaki, Papadopoulou, Basagana, Bustamante, Casas, Farzan, Fossati, Gonzalez, Grazuleviciene, Heude, Maitre, McEachan, Theologidis, Urquiza, Vafeiadi, West, Wright, McConnell, Vrijheid, Chatzi.
                Drafting of the manuscript: Stratakis, Conti, Urquiza, Vafeiadi, Wright, Chatzi.
                Critical revision of the manuscript for important intellectual content: Stratakis, Conti, Borras, Sabido, Roumeliotaki, Papadopoulou, Agier, Basagana, Bustamante, Casas, Farzan, Fossati, Gonzalez, Grazuleviciene, Heude, Maitre, McEachan, Theologidis, Vafeiadi, West, Wright, McConnell, Brantsaeter, Meltzer, Vrijheid, Chatzi.
                Statistical analysis: Stratakis, Conti, Borras, Papadopoulou, Agier, Basagana, Farzan, Gonzalez, Theologidis, Vafeiadi.
                Obtained funding: Grazuleviciene, McEachan, Wright, Meltzer, Vrijheid, Chatzi.
                Administrative, technical, or material support: Borras, Sabido, Roumeliotaki, Papadopoulou, Casas, McEachan, Urquiza, Vafeiadi, West, Wright, Brantsaeter, Meltzer, Chatzi.
                Supervision: Gonzalez, Wright, McConnell, Vrijheid, Chatzi.
                Conflict of Interest Disclosures: Dr Stratakis reported receiving grants from the National Institute for Health Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study. Dr Conti reported receiving grants from the National Institute for Health Sciences during the conduct of the study. Dr Fossati reported receiving grants from the European Commission during the conduct of the study. Dr McConnell reported receiving grants from the National Institute for Health Sciences during the conduct of the study. Dr Chatzi reported receiving grants from the National Institute for Health Sciences during the conduct of the study. No other disclosures were reported.
                Funding/Support: This study was supported by grant 308333 from the European Community Seventh Framework Programme; grant 874583 from the European Union Horizon 2020 Research and Innovation Programme; grant SEV-2012-0208 from the Centro de Excelencia Severo Ochoa 2013-2017, Spanish Ministry of Science, Innovation and Universities; grant 2017SGR595 from the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya; grant CB06/021/0041 from the Consorcio de Investigacion Biomedica en Red de Epidemiologia y Salud Publica; grant 1999SGR00241 from the Comissio Interdepartamental de Recerca i Innovacio Tecnologica, Generalitat de Catalunya; grant 31V-66 from the Lithuanian Agency for Science Innovation and Technology; grant PT17/0019 via the Plan Estatal de I+D+I 2013-2016 project from the Instituto de Salud Carlos III and the European Regional Development Fund; grants R21 ES029681 and P30 ES007048-23 from the National Institute for Health Sciences (Dr Stratakis); grant P30 DK048522-24 from the National Institute of Diabetes and Digestive and Kidney Diseases (Dr Stratakis); grants P01CA196569, R01CA140561, and R01 ES016813 from the National Institute for Health Sciences (Dr Conti); grant MS16/00128 from the Ministry of Economy and Competitiveness at the Instituto de Salud Carlos III (Dr Casas); grants R21 ES029681, P30 ES007048-23, and P01 ES022845 from the National Institute for Health Sciences (Dr McConnell); grant RD-83544101 from the Environmental Protection Agency (Dr McConnell); and grants R01 ES029944, R21 ES029681, R21 ES028903, and P30 ES007048-23 from the National Institute for Health Sciences (Dr Chatzi).
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Additional Contributions: Joane Quentin, PhD, Lise Giorgis-Allemand, PhD, and Remy Slama, PhD, of the EDEN study group from the University Grenoble-Alpes, France, assisted with the HELIX study data collection and management. Sonia Brishoual, BS, Angelique Serre, BS, and Michele Grosdenier BS, of Poitiers Biobank in Poitiers, France, provided biological sample management. Frederic Millot, PhD (principal investigator), Elodie Migault, BS, Manuela Boue, BS, and Sandy Bertin, BS, of the Clinical Investigation Center in Poitiers, France, assisted with planning and investigation. Isabella Annesi-Maesano, PhD, Jonathan Bernard, PhD, Jeremie Botton, PhD, Marie-Aline Charles, PhD, Patricia Dargent-Molina, PhD, Blandine de Lauzon-Guillain, PhD, Pierre Ducimetiere, PhD, Maria de Agostini, PhD, Bernard Foliguet, MD, Anne Forhan, PhD, Xavier Fritel, MD, Alice Germa, PhD, Valerie Goua, MD, Regis Hankard, MD, Monique Kaminski, PhD, Beactrice Larroque, PhD, Nathalie Lelong, MsC, Johanna Lepeule, PhD, Guillaume Magnin, MD, Laetitia Marchand, MsC, Catherine Nabet, MD, Fabrice Pierre, MD, Marie-Joseph Saurel-Cubizolles, PhD, Michel Schweitzer, MD, and Olivier Thiebaugeorges, MD, of the EDEN study group from the Institut National de la Sante et de la Recherche Medicale (Inserm) assisted with the EDEN study data collection and management. No compensation was received. We thank all of the field workers for their dedication and efficiency. We are grateful to all of the participating families in the Born in Bradford, EDEN, INMA, MoBa, and RHEA cohorts who took part in this study. The Born in Bradford study was only possible because of the enthusiasm and commitment of the participating children and parents; we thank all of the participants, health professionals, and researchers who made Born in Bradford happen. We thank all of the children and families who participated in the EDEN-HELIX mother-child cohort. We are also grateful to all of the participating families in Norway who are currently taking part in the ongoing MoBa cohort study.
                Article
                zoi200057
                10.1001/jamanetworkopen.2020.1007
                7076335
                32176304
                b288a9e4-a446-49c4-8778-d807f8c25fb5
                Copyright 2020 Stratakis N et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 1 August 2019
                : 27 January 2020
                Categories
                Research
                Original Investigation
                Online Only
                Nutrition, Obesity, and Exercise

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