Association of fish consumption and mercury exposure during pregnancy with metabolic health and inflammatory biomarkers in children
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. ; 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 Investigación Biomedica en Red de Epidemiologia y Salud Publica; grant 1999SGR00241 from the Comissió Interdepartamental de Recerca i Innovació 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)