Suchergebnisse

BACKGROUND: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. OBJECTIVES: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. METHODS: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother-child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. RESULTS: Questionnaires were completed by 37 cohort studies of > 350,000 mother-child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. CONCLUSION: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health. ; This work was supported by Environmental Health Risks in European Birth Cohorts (ENRIECO), a project conducted within the European Union's Seventh Framework Programme (Theme 6, Environment, including climate change), grant agreement 226285

Background: The impact of maternal diet during pregnancy on child neurodevelopment is of public health and clinical relevance. We evaluated the associations of dietary quality based on the Dietary Approaches to Stop Hypertension (DASH) score and dietary inflammatory potential based on the energy-adjusted Dietary Inflammatory Index (E-DII) score during pregnancy with emotional and behavioral symptoms of offspring at 7 to 10 years of age. Methods: Individual participant data for 11,870 mother-child pairs from four European cohorts participating in the ALPHABET project were analyzed. Maternal antenatal DASH and E-DII scores were generated from self-completed food frequency questionnaires. Symptoms of depression and anxiety, aggressive behavior, and attention-deficit/hyperactivity disorder in children were assessed using mother-reported tests and classified within the normal or borderline/clinical ranges using validated cutoffs. Adjusted odds ratios were determined by multivariable logistic regression models and aggregated by the two-level individual participant data meta-analysis method. Results: Higher maternal DASH scores (indicating better dietary quality) were associated with lower risk of depressive and anxiety symptoms, aggressive behavior symptoms, and attention-deficit/hyperactivity disorder symptoms within the borderline/clinical ranges: odds ratio [OR] 0.97, 95% confidence interval [CI], 0.95-0.99; OR 0.97, 95% CI, 0.94-0.99; OR 0.97, 95% CI, 0.95-0.98, per one-unit DASH score increase, respectively. For depression and anxiety, aggressive behavior, and attention-deficit/hyperactivity disorder symptoms, a one-unit increase in E-DII scores (a more proinflammatory diet) was associated with a 7% increased risk of all three analyzed emotional and behavioral symptoms: OR 1.07, 95% CI, 1.03-1.11; OR 1.07, 95% CI, 1.02-1.13; OR 1.07, 95% CI, 1.01-1.13, respectively. Conclusions: Our findings suggest that a maternal low-quality and proinflammatory diet may increase the risk of emotional and behavioral symptoms in children. ; This work was supported by an award from the European Union's Horizon 2020 research and innovation programme under the ERA-Net Cofund of the Joint Programming Initiative Healthy Diet for Healthy Life (JPI-HDHL) (http://www.healthydietforhealthylife.eu) action number 696295 (Biomarkers for Nutrition and Health). Cofunding was provided by Science Foundation Ireland, Ireland (Grant No. SFI/16/ERA-HDHL/3360 [to CMP]), the UK Biotechnology and Biological Sciences Research Council (ERA-HDHL Biomarkers: BBSRC BB/P028187/1 [to CR]), the Polish National Centre for Research and Development (ERA-HDHL/01/ALPHABET/1/2017 [to KP]), the ZonMw The Netherlands (Grant No. 529051014; 2017) ALPHABET project (Grant No. 696295; 2017 [to LD]) and the French National Agency of Research (reference AnrR16227KK [to BH]). ALSPAC: This work was supported by the UK Medical Research Council and Wellcome (Grant No. 102215/2/13/2) and the University of Bristol. This publication is the work of the authors and Matthew Suderman will serve as guarantors for the contents of this paper. EDEN: This work was supported by the Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR Cohorte Santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A), and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l'Education Nationale, a complementary health insurance (MGEN), French National Agency for Food Security, French-speaking Association for the Study of Diabetes and Metabolism (ALFEDIAM). Generation R: This work was supported by the Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Dr Liesbeth Duijts received funding from the European Union's Horizon 2020 cofunded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (ALPHABET project (Grant No. 696295; 2017), ZonMW The Netherlands (Grant No. 529051014; 2017). Dr. Hanan El Marroun was supported by Stichting Volksbond Rotterdam, the Dutch Brain Foundation (De Hersenstichting, project number GH2016.2.01), and NARSAD Young Investigator Grant No. 27853 from the Brain & Behavior Research Foundation. The project received funding from the European Union's Horizon 2020 Research and Innovation Programme (LIFECYCLE project, Grant No. 733206; 2016). REPRO_PL: This work was supported by the Ministry of Science and Higher Education, Poland (PBZ-MEiN-/8/2//2006; Contract No. K140/P01/2007/1.3.1.1); by the grant PNRF-218-AI-1/07 from Norway through the Norwegian Financial Mechanism within the Polish-Norwegian Research Fund, National Science Centre under the call of JPI HDHL Nutrition and Cognitive Function (2015/17/Z/NZ7/04273), and the National Science Centre, Poland (DEC-2014/15/B/NZ7/00998). Mònica Guxens (CPII18/00018) and Maribel Casas (CP16/00128) are funded by a Miguel Servet fellowship (from the Spanish Institute of Health Carlos III). We acknowledge support from the Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019–2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Programme.

BACKGROUND: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth. OBJECTIVES: We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery. METHODS: Using individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates. RESULTS: Eleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy, based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW [odds ratio (OR) = 1.25; 95% CI: 1.04, 1.49], as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR = 2.11; 95% CI: 1.10, 4.06 for exposure to four or more EDC groups). There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation. CONCLUSION: Results from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW. ; This work was supported by the European Community's Seventh Framework Programme (grants FP7/2007-2013, 226285, 241604) as part of the Environmental Health Risks in European Birth Cohorts project (http://www.enrieco.org) and the Developing a Child Cohort Research Strategy for Europe project (http://www.chicosproject.eu); and by the Instituto de Salud Carlos III (grant CD12/00563). Funding per cohort: ABCD: This work was supported by the Netherlands Organization for Health Research and Development (grant 2100.0076). BAMSE: This work was supported by the Swedish Heart-Lung Foundation; Stockholm County Council; Swedish Research Council for Health, Working Life and Welfare; and the European Commission's Seventh Framework 29 Program: the Mechanisms of the Development of Allergy (grant 261357). DNBC: This work was supported by the Danish Epidemiology of Science Centre; Pharmacy Foundation; Egmont Foundation; March of Dimes Birth Defect Foundation; Agustinus Foundation; and the Health Foundation. Generation R: This work was supported by the Erasmus Medical Center Rotterdam; Netherlands Organization for Health Research and Development; European Commission Seventh Framework Programme; and the Contaminant Mixtures and Human Reproductive Health Project (grant 212502); V.J. received an additional grant from the Netherlands Organization for Health Research and Development (grant VIDI 016.136.361) and Consolidator Grant from the European Research Council (grant ERC-2014-CoG-648916). Generation XXI: This work was supported by the Programa Operacional de Saúde – Saúde XXI; Quadro Comunitário de Apoio III; Administração Regional de Saúde Norte (Regional Department of Ministry of Health); Portuguese Foundation for Science and Technology; Fundo Europeu de Desenvolvimento Regional, and the Calouste Gulbenkian Foundation. INMA_Granada: This work was supported by the Instituto de Salud Carlos III (grants G03/176, CB06/02/0041); Spanish Ministry of Health (grant FIS-07/0252); European Union Commission (grants QLK4-1999-01422, QLK4-2002-00603, FP7-ENV-212502); and the Consejería de Salud de la Junta de Andalucía (grant 183/07; 0675-2010). INMA_New: This work was supported by the European Union (grants FP7-ENV-2011, 282957, HEALTH.2010.2.4.5-1); Instituto de Salud Carlos III (grants G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI06/0867, FIS-PS09/00090); Conselleria de Sanitat Generalitat Valenciana; Spanish Ministry of Health (grants FIS-PI041436, FIS- PI081151, FIS-PI042018, FIS-PI09/02311); Generalitat de Catalunya (grants CIRIT1999SGR, 00241); Obre Social Cajastur; Universidad de Oviedo; Department of Health of the Basque Government (grants 2005111093, 2009111069); and the Provincial Government of Gipuzkoa (grants DFG06/004, DFG08/001). KANC: This work was supported by the European Commission (grant FP6-036224). MoBa: This work was supported by the Norwegian Ministry of Health; National Institutes of Health; National Institute of Environmental Health Sciences (grant N01-ES–85433); National Institute of Neurological Disorders and Stroke (grant 1 UO1 NS 047537); Norwegian Research Council; Functional Genomics (grant 151918/S10); and Environmental Exposures and Health Outcomes (grant 213148). NINFEA: This work was supported by the Compagnia San Paolo Foundation, and by the Piedmont Region. Pélagie: This work was supported by the National Institute of Health and Medical Research; the French Ministry of Health; the French Ministry of Labor; French Agency for Food, Environmental and Occupational Health and Safety; French National Research Agency; and the French Institute for Public Health Surveillance. REPRO_PL: This work was supported by the National Centre for Research and Development, Poland (grants PBZ-MEiN-/8/2/2006, K140/P01/2007/1.3.1.1); the Norwegian Financial Mechanism within the PolishNorwegian Research Fund (grant PNRF-218-AI-1/07); and European Community's Seventh Framework Programme (grant FP7/2007-2013, 603946). Rhea: This work was supported by the European Union Integrated Project NewGeneris, 6th Framework Programme, (grant FOOD-CT-2005-016320); and the Health Impacts of Long-term Exposure to Disinfection By-products in Drinking Water project (grant Food-CT-2006-036224).

Data de publicació electrònica: 10-02-2022 ; Background: Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. Objective: Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. Methods: We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. Results: The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. Conclusion: Our findings do not support early-life cat and dog ownership in ...

Background: In utero exposure to bisphenols, widely used in consumer products, may alter lung development and increase the risk of respiratory morbidity in the offspring. However, evidence is scarce and mostly focused on bisphenol A (BPA) only. Objective: To examine the associations of in utero exposure to BPA, bisphenol F (BPF), and bisphenol S (BPS) with asthma, wheeze, and lung function in school-age children, and whether these associations differ by sex. Methods: We included 3,007 mother-child pairs from eight European birth cohorts. Bisphenol concentrations were determined in maternal urine samples collected during pregnancy (1999-2010). Between 7 and 11 years of age, current asthma and wheeze were assessed from questionnaires and lung function by spirometry. Wheezing patterns were constructed from questionnaires from early to mid-childhood. We performed adjusted random-effects meta-analysis on individual participant data. Results: Exposure to BPA was prevalent with 90% of maternal samples containing concentrations above detection limits. BPF and BPS were found in 27% and 49% of samples. In utero exposure to BPA was associated with higher odds of current asthma (OR = 1.13, 95% CI = 1.01, 1.27) and wheeze (OR = 1.14, 95% CI = 1.01, 1.30) (p-interaction sex = 0.01) among girls, but not with wheezing patterns nor lung function neither in overall nor among boys. We observed inconsistent associations of BPF and BPS with the respiratory outcomes assessed in overall and sex-stratified analyses. Conclusion: This study suggests that in utero BPA exposure may be associated with higher odds of asthma and wheeze among school-age girls. ; The research leading to these results has received funding from Instituto de Salud Carlos III and European Union's FEDER funds (CP16/00128 – the ENDOLUNG project, and PI17/01194 – the INMA-Ado-Respi Project), the European Community's Seventh Framework Programme (FP7/2007–206) under grant agreement no 308,333 - the HELIX project –, and from the EC's Horizon 2020 research and innovation programme under grant agreement No 874,583 – the ATHLETE project. Generation R: This study was funded by The Erasmus MC, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement No 733206, 2016; EUCAN-Connect grant agreement No 824989; ATHLETE, grant agreement No 874583). Dr. Vincent Jaddoe received a grant from the European Research Council (ERC-2014-CoG-648916). This study was supported by grant R01-ES022972 and R01-ES029779 from the National Institutes of Health, USA. The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data, or writing of this report. INMA Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI13/02187 and FIS-PI18/01142 incl. FEDER funds), CIBERESP, Department of Health of the Basque Government (2015111065), and the Provincial Government of Gipuzkoa (DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). INMA Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l'Alimentation de l'Environnement et du Travail (1262C0010), European Commission (261357, 308333, 603,794 and 634453). Alicia Abellan holds a LifeCycle fellowship, funded from the European Union's Horizon 2020 research and innovation programme under grant agreement No 733206. Maribel Casas holds a Miguel Servet fellowship (CP16/00128) funded by Instituto de Salud Carlos III and co-funded by European Social Fund "Investing in your future". We acknowledge support from the Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019–2023" Program (2018–000806-S), and support from the Generalitat de Catalunya through the CERCA Program. INMA Valencia: INMA Valencia was funded by Grants from UE (FP7-ENV-2011 cod 282,957 and HEALTH.2010.2.4.5–1), Spain: ISCIII (G03/176; FIS-FEDER: PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663, and PI19/1338; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051), Alicia Koplowitz Foundation, and Generalitat Valenciana: FISABIO (UGP 15–230, UGP-15–244, UGP-15–249, and AICO/2020/285). BiB: This report is independent research funded by the National Institute for Health Research Yorkshire and Humber ARC (NIHR200166) and BiB receives core infrastructure funding from the Wellcome Trust (WT101597MA). The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. EDEN: The EDEN study was supported by Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A), and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l'Education Nationale a complementary health insurance (MGEN), French national agency for food security, French-speaking association for the study of diabetes and metabolism (ALFEDIAM). MoBa: The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. RHEA: The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211,250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226,285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308,333 HELIX, H2020 LIFECYCLE, grant agreement No 733206, H2020 ATHLETE, grant agreement No 874583), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; "Rhea Plus": Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). Additional funding from NIEHS supported Dr Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, R21ES028903, and P30ES007048). The funding sources had no involvement in the study design, the collection, analysis and interpretation of data or in the writing of the report and in the decision to submit the article for publication.

The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother-child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4-12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07-1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07-1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use. ; DAL's contribution to this paper is supported by the European Research Council under the European Union's Seventh Framework Programme (FP7/2007–2013/ERC grant agreement no 669545) and a UK National Institute of Health Senior Investigator (NF-0616-10102). TC's contribution is supported by European Union's Horizon 2020 research and innovation programme under grant agreement No 733206 (LifeCycle). DAL and TC work in a Unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_00011/6). The Danish National Birth Cohort (DNBC) was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation. Follow-up of mothers and children have been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B), the Lundbeck Foundation (195/04, R100-A9193), the Innovation Fund Denmark 0603-00294B (09-067124), the Nordea Foundation (02-2013-2014), Aarhus Ideas (AU R9-A959-13-S804), University of Copenhagen Strategic Grant (IFSV 2012), and the Danish Council for Independent Research (DFF—4183-00594 and DFF—4183-00152). The Gene and Environment: Prospective Study on Infancy in Italy (GASPII) was funded by the Italian Ministry of Health and by the Italian Medicines Agency. The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research (NWO), the Ministry of Health, Welfare, and Sport, and the Ministry of Youth and Families. This study was supported by the NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation grant number 27853 (HEM), Vici project 016.VICI.170.200 (HT). MLV has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 707404. The opinions expressed in this document reflect only the author's view. The European Commission is not responsible for any use that may be made of the information it contains. The INfancia y Medio Ambiente (INMA)-Sabadell cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; CP18/00018; PI041436; PI081151; PI1100610 incl. FEDER funds), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430). ISGlobal acknowledge support from the Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019–2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness (IJCI-2017-34068). JJ holds Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (Co-funded by European Social Fund "Investing in your future"). MC holds a Miquel Servet-I cotract (CP16/00128) awarded by the Instituto de Salud Carlos III (co-funded by European Social Fund "Investing in your future"). The INMA-Asturias cohort is funded by grants from Instituto de Salud Carlos III (FISS PI 04/2018, FIISPI09/02311, FISSPI13/02429, FISS PI18/00909 including FEDER funds) and University of Oviedo. This study was funded by Instituto de Salud Carlos III through the projects 'CP14/00108 & PI16/00261' (co-funded by European Regional Development Fund 'A way to make Europe') and CIBERESP, Obra Social Cajastur/Fundación Liberbank. The INMA-Gipuzkoa was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090, FIS-PI18/01142 and FIS-PI13/02187 incl. FEDER funds), Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). The INMA-Valencia was funded by Grants from European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5–1), Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051), Generalitat Valenciana: FISABIO (UGP 15–230, UGP-15–244, and UGP-15–249), and Alicia Koplowitz Foundation 2017. The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7- 2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH- 2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EUFP7- HEALTH-2012 Proposal No 308333 HELIX, FP7 European Union project, No. 264357 MeDALL), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; Rhea Plus: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). LC was supported by the National Institute of Environmental Health Sciences (R01ES029944, R01ES030364, R21ES28903, R21ES029681, P30ES007048).

Exposure to chemical substances that can produce endocrine disrupting effects represents one of the most critical public health threats nowadays. In line with the regulatory framework implemented within the European Union (EU) to reduce the levels of endocrine disruptors (EDs) for consumers, new and effective methods for ED testing are needed. The OBERON project will build an integrated testing strategy (ITS) to detect ED-related metabolic disorders by developing, improving and validating a battery of test systems. It will be based on the concept of an integrated approach for testing and assessment (IATA). OBERON will combine (1) experimental methods (in vitro, e.g., using 2D and 3D human-derived cells and tissues, and in vivo, i.e., using zebrafish at different stages), (2) high throughput omics technologies, (3) epidemiology and human biomonitoring studies and (4) advanced computational models (in silico and systems biology) on functional endpoints related to metabolism. Such interdisciplinary framework will help in deciphering EDs based on a mechanistic understanding of toxicity by providing and making available more effective alternative test methods relevant for human health that are in line with regulatory needs. Data generated in OBERON will also allow the development of novel adverse outcome pathways (AOPs). The assays will be pre-validated in order to select the test systems that will show acceptable performance in terms of relevance for the second step of the validation process, i.e., the inter-laboratory validation as ring tests. Therefore, the aim of the OBERON project is to support the organization for economic co-operation and development (OECD) conceptual framework for testing and assessment of single and/or mixture of EDs by developing specific assays not covered by the current tests, and to propose an IATA for ED-related metabolic disorder detection, which will be submitted to the Joint Research Center (JRC) and OECD community. ; The authors would like to acknowledge OBERON (https://oberon-4eu.com/, a project funded by the European Union's Horizon 2020 research and innovation program under grant agreement no. 825712.

Background: Infant weight gain is associated with lower lung function and a higher risk of childhood asthma. Detailed individual childhood growth patterns might be better predictors of childhood respiratory morbidity than the difference between two weight and height measurements. We assessed the associations of early childhood growth patterns with lung function and asthma at the age of 10 years and whether the child's current body mass index (BMI) influenced any association. Methods: We derived peak height and weight growth velocity, BMI at adiposity peak, and age at adiposity peak from longitudinally measured weight and height data in the first 3 years of life of 4435 children enrolled in a population-based prospective cohort study. At 10 years of age, spirometry was performed and current asthma was assessed by questionnaire. Spirometry outcomes included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and forced expiratory flow after exhaling 75% of vital capacity (FEF75). Results: Greater peak weight velocity was associated with higher FVC but lower FEV1/FVC and FEF75. Greater BMI at adiposity peak was associated with higher FVC and FEV1 but lower FEV1/FVC and FEF75. Greater age at adiposity peak was associated with higher FVC, FEV1, FEV1/FVC and FEF75, particularly in children with a small size at birth, and lower odds of current asthma in boys. The child's current BMI only explained the associations of peak weight velocity and BMI at adiposity peak with FVC and FEV1. Peak height velocity was not consistently associated with impaired lung function or asthma. Conclusion: Peak weight velocity and BMI at adiposity peak were associated with reduced airway patency in relation to lung volume, whereas age at adiposity peak was associated with higher lung function parameters and lower risk of asthma at 10 years, particularly in boys. ; The Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam, Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Dr Liesbeth Duijts received additional funding from the European Union's Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (ALPHABET project (no. 696295; 2017), ZonMW The Netherlands (no. 529051014; 2017)). The study was supported by the Netherlands Organization for Health Research and Development (VIDI 016.136.361), a European Research Council Consolidator Grant (ERC-2014-CoG-648916), funding from the European Union's Seventh Framework Programme under grant agreement no. 289346 (EarlyNutrition), and funding from the European Union's Horizon 2020 research and innovation programme under grant agreements no. 733206 (LifeCycle) and no. 633595 (DynaHEALTH). Dr Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (CD12/00563 and MS16/00128). The researchers are independent from the funders.

Characterization of the "exposome", the set of all environmental factors that one is exposed to from conception onwards, has been advocated to better understand the role of environmental factors on chronic diseases. Here, we aimed to describe the early-life exposome. Specifically, we focused on the correlations between multiple environmental exposures, their patterns and their variability across European regions and across time (pregnancy and childhood periods). We relied on the Human Early-Life Exposome (HELIX) project, in which 87 environmental exposures during pregnancy and 122 during the childhood period (grouped in 19 exposure groups) were assessed in 1301 pregnant mothers and their children at 6-11 years in 6 European birth cohorts. Some correlations between exposures in the same exposure group reached high values above 0.8. The median correlation within exposure groups was >0.3 for many exposure groups, reaching 0.69 for water disinfection by products in pregnancy and 0.67 for the meteorological group in childhood. Median correlations between different exposure groups rarely reached 0.3. Some correlations were driven by cohort-level associations (e.g. air pollution and chemicals). Ten principal components explained 45% and 39% of the total variance in the pregnancy and childhood exposome, respectively, while 65 and 90 components were required to explain 95% of the exposome variability. Correlations between maternal (pregnancy) and childhood exposures were high (>0.6) for most exposures modeled at the residential address (e.g. air pollution), but were much lower and even close to zero for some chemical exposures. In conclusion, the early life exposome was high dimensional, meaning that it cannot easily be measured by or reduced to fewer components. Correlations between exposures from different exposure groups were much lower than within exposure groups, which have important implications for co-exposure confounding in multiple exposure studies. Also, we observed the early life exposome to be variable over time and to vary by cohort, so measurements at one time point or one place will not capture its complexities. ; This work was supported by the European Commission Seventh Framework Programme (FP7/2007–2013) [grant number: 308333–the HELIX project]. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537-01 and grant no.2 UO1 NS 047537-06A1). The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EUFP7-HEALTH-2012 Proposal No 308333 HELIX, FP7 European Union project, No. 264357 MeDALL), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; "Rhea Plus": Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15).

Background: Few studies have investigated the 24-hour respiratory health effects of personal black carbon (BC) and ultrafine particles (UFP) exposure in schoolchildren. The objective of this study was to investigate these associations with the lung function in children 10-years old with and without persistent respiratory symptoms. Methods: We conducted a cross-sectional study in 305 children (147 and 158 with and without persistent respiratory symptoms, respectively) from three European birth-cohorts: PARIS (France) and INMA Sabadell and Valencia (Spain). Personal 24-hour measurements of exposure concentrations to BC and UFP were performed by portable devices, before lung function testing. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the fraction of exhaled nitric oxide (FeNO) were determined. Results: There was no association of UFP with lung function parameters or FeNO whereas the increase in 24-hour BC exposure concentrations was related to a statistically significant decrease in lung function parameters only among children with persistent respiratory symptoms [-96.8 mL (95% Confidence Interval CI: -184.4 to -9.1 mL) in FVC, and -107.2 mL (95% CI: -177.5 to -36.9 mL) in FEV1 for an inter-quartile range of 1160 ng/m3 exposure increase]. A significant positive association between BC and FeNO was observed only in children with persistent respiratory symptoms with current wheezing and/or medication to improve breathing [FeNO increases with +6.9 ppb (95% CI: 0.7 to 13.1 ppb) with an inter-quartile range BC exposure increase]. Conclusion: Children suffering from persistent respiratory symptoms appear to be more vulnerable to BC exposure. ; The study in Sabadell was funded by grants from Instituto de Salud Carlos III Red INMA (G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 19995GR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació la Marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), EU Commission (261357, 308333 and 603794), the European Community's Seventh Framework Programme (FP7/2007/2013) under grant agreements 308333-HELIX Project and 308610-EXPOSOMICS Project. Dr Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128). The study in Valencia was funded by grants from European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: Instituto de Salud Carlos III (FIS-FEDER funds: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/02032, PI14/00891, PI14/01687, and PI16/1288; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051), and Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249).

Introduction: Early onset and high prevalence of allergic diseases result in high individual and socio-economic burdens. Several studies provide evidence for possible effects of environmental factors on allergic diseases, but these are mainly single-exposure studies. The exposome provides a novel holistic approach by simultaneously studying a large set of exposures. The aim of the study was to evaluate the association between a broad range of prenatal and childhood environmental exposures and allergy-related outcomes in children. Material and methods: Analyses of associations between 90 prenatal and 107 childhood exposures and allergy-related outcomes (last 12 months: rhinitis and itchy rash; ever: doctor-diagnosed eczema and food allergy) in 6-11 years old children (n = 1270) from the European Human Early-Life Exposome cohort were performed. Initially, we used an exposome-wide association study (ExWAS) considering the exposures independently, followed by a deletion-substitution-addition selection (DSA) algorithm considering all exposures simultaneously. All the exposure variables selected in the DSA were included in a final multi-exposure model using binomial general linear model (GLM). Results: In ExWAS, no exposures were associated with the outcomes after correction for multiple comparison. In multi-exposure models for prenatal exposures, lower distance of residence to nearest road and higher di-iso-nonyl phthalate level were associated with increased risk of rhinitis, and particulate matter absorbance (PMabs) was associated with a decreased risk. Furthermore, traffic density on nearest road was associated with increased risk of itchy rash and diethyl phthalate with a reduced risk. DSA selected no associations of childhood exposures, or between prenatal exposures and eczema or food allergy. Discussion: This first comprehensive and systematic analysis of many environmental exposures suggests that prenatal exposure to traffic-related variables, PMabs and phthalates are associated with rhinitis and itchy rash. ; This work was supported by the European Community's Seventh Framework Programme [grant agreement no 308333—the HELIX project]; Instituto de Salud Carlos III; CIBERESP; Conselleria de Sanitat; Generalitat Valenciana; Department of Health of the Basque Government; Provincial Government of Gipuzkoa; Generalitat de Catalunya-CIRIT; Lithuanian Agency for Science Innovation and Technology [grant number 6-04-2014_31V-66]; Norwegian Ministry of Health and Care Services; Norwegian Ministry of Education and Research; Greek Ministry of Health; Ministerio de Ciencia Innovacion y Universidades [grant number MTM2015-68140-R]; Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII; Fondation de France.

BACKGROUND: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction. OBJECTIVE: We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (NO2) exposure and birth weight. METHODS: We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis. RESULTS: Pooled estimates indicated that a 10-μg/m3 increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: -9.3, -0.3%) and a 48-g decrease (95% CI: -87, -9 g) in birth weight. However, the association with birth weight was significant for INMA (-66 g; 95% CI: -111, -23 g) but not for ENVIRONAGE (-20 g; 95% CI: -101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content. CONCLUSION: Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight. ; The research leading to these results was funded by the Spanish Ministry of Health (FIS-PI11/00610, FIS-PI041436, FIS-PI081151, FIS-PI042018, and FIS-PI09/02311), the European Union (EU) (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI06/0867, and FIS-PS09/00090), the Conselleria de Sanitat Generalitat Valenciana, the Generalitat de Catalunya-CIRIT (1999SGR 00241), the Obre Social Cajastur, the Universidad de Oviedo, the Department of Health of the Basque Government (2005111093 and 2009111069), and the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). The ENVIRONAGE cohort is supported by the EU Program "Ideas" (ERC-2012- StG 310898) and by the Flemish Fund for Scientific Research (FWO 1516112N and G073315N).

BackgroundMaternal pre-pregnancy obesity may impair infant neuropsychological development, but it is unclear whether intrauterine or confounding factors drive this association.MethodsWe assessed whether maternal pre-pregnancy obesity was associated with neuropsychological development in 1,827 Spanish children. At 5 years, cognitive and psychomotor development was assessed using McCarthy Scales of Children's Abilities, attention deficit hyperactivity disorder (ADHD) symptoms using the Criteria of Diagnostic and Statistical Manual of Mental Disorders, and autism spectrum disorder symptoms using the Childhood Asperger Syndrome Test. Models were adjusted for sociodemographic factors and maternal intelligence quotient. We used paternal obesity as negative control exposure as it involves the same source of confounding than maternal obesity.ResultsThe percentage of obese mothers and fathers was 8% and 12%, respectively. In unadjusted models, children of obese mothers had lower scores than children of normal weight mothers in all McCarthy subscales. After adjustment, only the verbal subscale remained statistically significantly reduced (β: -2.8; 95% confidence interval: -5.3, -0.2). No associations were observed among obese fathers. Maternal and paternal obesity were associated with an increase in ADHD-related symptoms. Parental obesity was not associated with autism symptoms.ConclusionMaternal pre-pregnancy obesity was associated with a reduction in offspring verbal scores at pre-school age. ; This study was funded by grants from European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1)

Background: Humans are regularly exposed to metals and metalloids present in air, water, food, soil and domestic materials. Most of them can cross the placental barrier and cause adverse impacts on the developing foetus. Objectives: To describe the prenatal concentrations of metals and metalloids and to study the associated sociodemographic, environmental and dietary factors in pregnant Spanish women. Methods: Subjects were 1346 pregnant women of the INMA Project, for whom the following metals arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), thallium (Tl) and zinc (Zn) were determined in urine, at both the first and the third trimesters of gestation. Sociodemographic, dietary and environmental information was collected through questionnaires during pregnancy. Multiple linear mixed models were built in order to study the association between each metal and metalloid concentrations and the sociodemographic, environmental and dietary factors. Results: The most detected compounds were As, Co, Mo, Sb, Se and Zn at both trimesters. Zn was the element found in the highest concentrations at both trimesters and Tl was detected in the lowest concentrations. We observed significant associations between As, Cd, Cu, Sb, Tl and Zn concentrations and working situation, social class and age. Seafood, meat, fruits, nuts, vegetables and alcohol intake affected the levels of all the metals but Cd and Cu. Proximity to industrial areas, fields and air pollution were related to all metals except Cd, Sb and Se. Conclusions: This is the first large prospective longitudinal study on the exposure to metals and metalloids during pregnancy and associated factors to include several cohorts in Spain. The present study shows that some modifiable lifestyles, food intakes and environmental factors could be associated with prenatal exposure to metal(loid)s, which may be considered in further studies to assess their relationship with neonatal health outcomes. ; This study was funded by Grants from EU (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5–1); Spain: ISCIII (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/00090, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI13/02187, PI14/00891, PI14/01687, PI16/1288, PI17/00663, PI18/01142 and PI19/1338; Miguel Servet FEDER MS15/00025, MS20/0006, CPII16/00051, and FIS-FSE: 17/ 00260); CIBERESP; Generalitat Valenciana: FISABIO (UGP 15–230, UGP-15-244, and UGP-15-249), AICO/2020/285, and Alicia Koplowitz Foundation 2017; Generalitat de Catalunya-CIRIT 1999SGR 00241; Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065); Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221).

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)