Suchergebnisse

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood. ; This work was partially supported by the Southern California Environmental Health Sciences Center (grant # P30ES007048) funded by the National Institute of Environmental Health Sciences [PI Gilliland]. Dr. Contreras was supported by a grant from the NIH T32ES013678. MEDALL and CHICOS Projects: The research leading to these results has received funding from the European Community's Seventh Framework Program(Health–F2-grantagreements No. 261357 and 241604). Per cohort ABCD: Data of the Amsterdam Born Children and their Development cohort study used in this research was in part supported by funds from the Netherlands Organisation for Health Research and Development (ZonMw 40–00812-98–11010). The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. BAMSE: We acknowledge all funding sources: The Swedish Research Council, The Swedish Heart and Lung Foundation, The Swedish Research Council for Working Life and Social Welfare, the Swedish Asthma and Allergy Association Research Foundation, The Swedish Research Council Formas, Stockholm County Council, and the European Commission's Seventh Framework 29 Program Me DALL under grant agreement No.261357. We thank all the children and their parents for participating in the BAMSE cohort and the nurses and other staff members working in the BAMSE project. EDEN: We acknowledge all the funding sources for the EDEN study: 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 FP7programmes (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 ofdiabetes and metabolism (ALFEDIAM).We acknowledge the commitment of the EDEN mother-child cohort study group: I.Annesi-Maesano, JY. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, , A. Forhan, X. Fritel, A. Germa, V.Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G.Magnin, L. Marchand, C. Nabet, F. Pierre, R. Slama, M.J. Saurel-Cubizolles, M.Schweitzer, O. Thiebaugeorges.The Generation R Study: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 Organisation for Scientific Research (NWO), the Ministry of Health, Welfareand Sport and the Ministry of Youth and Families. The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE project, grant agreement no 733206; 2016), the European Research Council (ERC-2014-CoG-648916) and from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERAHDHL), Horizon 2020 (grant agreement no 696295; 2017), ZonMW The Netherlands (no529051014; 2017), Science Foundation Ireland (no SFI/16/ERA-HDHL/3360), and the European Union (ALPHABET project).The researchers are independent from the funders. The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. INMA: Data used for this research was provided by the INMA-Environment and Childhood Project (www.proyectoinma.org). This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), Spanish Ministry of Health (FIS-PIO41436, PI06/0867, PI081151, and FIS-FEDER 03/1615, 04/1112,04/1931, 05/1079, 05/1052, 06/1213, 07/0314 and 09/02647), Generalitat de Catalunya-CIRIT 1999SGR00241, the Conselleria de Sanitat Generalitat Valenciana, Department of Health of the Basque Government (2005111093 and 2009111069), the ProvincialGovernment of Gipuzkoa (DFG06/004 and DFG08/001).KOALA: The collection of the data from the KOALA Birth Cohort Study used in this analysis was financially supported by Friesland Foods (now Friesland Campina),Netherlands Asthma Foundation (grant numbers 3.2.07.022 and 3.2.03.48), Netherlands Heart Foundation (grant number 2014 T037, the Netherlands Organization for Health Research and Development (Zon Mw Prevention Program number 1.210-00-090), Triodos Foundation, Phoenix Foundation, Raphaël Foundation, Iona Foundation, Foundation forthe Advancement of Heilpedagogie, all in the Netherlands. MAS:The MAS birth cohort was funded by grants from the German Federal Ministry ofEducation and Research (BMBF; reference numbers 07015633, 07 ALE 27, 01EE9405/5,01EE9406) and the German Research Foundation (DFG; reference number KE 1462/2-1).PIAMA: The PIAMA study has been funded by The Netherlands Organisation for Health Research and Development; The Netherlands Organisation for Scientific Research; The Netherlands Asthma fund; The Netherlands Ministry of Spatial Planning Housing, and the Environment; and The Netherlands Ministry of Health, Welfare and Sport. RHEA: The Rhea project was financially supported by European projects (EU FP6-003-Food-3-NewGeneris -Contract No16320, EU FP6 STREP Hiwate -Contract No36224,EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers Contract No226756, EU FP7-HEALTH-2009-single stage CHICOS Contract No241604, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU-FP7,Proposal No 264357 MeDALL, EU- FP7-HEALTH-2012 Proposal No 308333 HELIX),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": Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-2015).ROBBIC: Data of the Rome cohort was in part supported byfunds from the Italian Ministry of Health (Programma speciale ex art. 12, comma 2, lettera b) del D. Lgs. 502/92,2001, 2003). We thank all the fields workers and the families for their contribution to thestudy. SWS: We thank the members of the Southampton Women's Survey Study group and the many participants in the SWS for their contribution to the study. The Southampton Women's Survey is supported by grants from the Medical Research Council, British Heart Foundation, Food Standards Agency, British Lung Foundation, Arthritis Research UK, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, and the European Union's Seventh Framework Programme (FP7/2007-2013), project Early Nutrition under grant agreement n°289346.

BACKGROUND: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. OBJECTIVES: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. METHODS: Ours was a collaborative study of four European population-based birth/child cohorts-CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and between 2.5 and 10 μm (PMcoarse), and PM2.5 absorbance were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods. We quantitatively assessed autistic traits when the child was between 4 and 10 years of age. Children were classified with autistic traits within the borderline/clinical range and within the clinical range using validated cut-offs. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. RESULTS: A total of 8,079 children were included. Prenatal air pollution exposure was not associated with autistic traits within the borderline/clinical range (odds ratio = 0.94; 95% CI: 0.81, 1.10 per each 10-μg/m3 increase in NO2 pregnancy levels). Similar results were observed in the different cohorts, for the other pollutants, and in assessments of children with autistic traits within the clinical range or children with autistic traits as a quantitative score. CONCLUSIONS: Prenatal exposure to NO2 and PM was not associated with autistic traits in children from 4 to 10 years of age in four European population-based birth/child cohort studies. ; Funding was provided as follows: ESCAPE Project— European Community's Seventh Framework Program (FP7/2007-2011-GA#211250). CATSS, Sweden— Swedish Research Council for Health, Working Life and Welfare (FORTE), Swedish Research Council (VR) Formas, in partner hip with FORTE and VINNOVA (cross-disciplinary research program concerning children's and young people's mental health); VR through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant 340-2013-5867; HKH Kronprinsessan Lovisas förening för barnasjukvård; and the Strategic Research Program in Epidemiology at Karolinska Institutet. Generation R, the Netherlands—The Generation R Study is conducted by the Erasmus University Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The general design of the Generation R Study is made possible by financial support from the Erasmus University Medical Center, Rotterdam; the Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Organization for Scientific Research (NWO); and the Ministry of Health, Welfare and Sport. The Netherlands Organisation for Applied Scientific Research (TNO) received funding from the Netherlands Ministry of Infrastructure and the Environment to support exposure assessment. GASPII, Italy—grant from the Italian Ministry of Health (ex art.12, 2001). INMA, Spain— grants from Instituto de Salud Carlos III (Red INMA G03/176 and 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-PI041436, FIS-PI081151, FIS-PI06/0867, FIS-PS09/00090), PI13/1944, PI13_02032, PI14/0891, PI14/1687, MS13/00054, UE (FP7-ENV-2011 cod 282957, and HEALTH.2010.2.4.5-1); Generalitat de Catalunya-CIRIT 1999SGR 00241; La Fundació La Marató de TV3 (090430); Conselleria de Sanitat Generalitat Valenciana; Department of Health of the Basque Government (2005111093 and 2009111069); and Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). V.W.V.J. received an additional grant from the Netherlands Organization for Health Research and Development (ZonMw 90700303, 916.10159). A.G.'s work was supported by a research grant from the European Community's 7th Framework Programme (FP7/2008–2013-GA#212652). A full roster of the INMA project investigators can be found online (http://www. proyectoinma.org/presentacion-inma/listado-investigadores/ en_listado-investigadores.html).

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)

Background: There is increasing interest in the potential effects of polybrominated diphenyl ethers (PBDEs) on children's neuropsychological development, but only a few small studies have evaluated such effects. Objectives: Our goal was to examine the association between PBDE concentrations in colostrum and infant neuropsychological development and to assess the influence of other persistent organic pollutants (POPs) on such association. Methods: We measured concentrations of PBDEs and other POPs in colostrum samples of 290 women recruited in a Spanish birth cohort. We tested children for mental and psychomotor development with the Bayley Scales of Infant Development at 12–18 months of age. We analyzed the sum of the seven most common PBDE congeners (BDEs 47, 99, 100, 153, 154, 183, 209) and each congener separately. Results: Increasing Σ7PBDEs concentrations showed an association of borderline statistical significance with decreasing mental development scores (β per log ng/g lipid = –2.25; 95% CI: –4.75, 0.26). BDE-209, the congener present in highest concentrations, appeared to be the main congener responsible for this association (β = –2.40, 95% CI: –4.79, –0.01). There was little evidence for an association with psychomotor development. After adjustment for other POPs, the BDE-209 association with mental development score became slightly weaker (β = –2.10, 95% CI: –4.66, 0.46). Conclusions: Our findings suggest an association between increasing PBDE concentrations in colostrum and a worse infant mental development, particularly for BDE-209, but require confirmation in larger studies. The association, if causal, may be due to unmeasured BDE-209 metabolites, including OH-PBDEs (hydroxylated PBDEs), which are more toxic, more stable, and more likely to cross the placenta and to easily reach the brain than BDE-209. ; This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-PI06/0867, and FIS-PS09/00090), Spanish Ministry of Health (FIS-PI041436 and FIS- PI081151), Generalitat de Catalunya-CIRIT (1999SGR 00241), Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), and Fundación Roger Torné

Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health. Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12–18 months of age in a Spanish birth cohort of 2,199 infants. Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO2) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations. Results: A 10-µg/m3 increase in average NO2 during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO2 were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO2, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period. Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants. ; This study was funded by grants from Spanish Ministry of Health–Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-PI041436, FIS- PI081151, FIS-PI042018, FIS-PI09/02311, FIS-PI06/0867, FIS-PS09/00090, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, and 09/02647), Generalitat de Catalunya-CIRIT (Consejo Interdepartamental de Investigación e Innovación Tecnológica) (1999SGR 00241), Conselleria de Sanitat Generalitat Valenciana, Universidad de Oviedo, Obra social Cajastur, Department of Health of the Basque Government (2005111093 and 2009111069), Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), and Fundación Roger Torné. M.P. holds a Juan de la Cierva post-doctoral fellowship awarded from the Spanish Ministry of Science and Innovation (JCI-2011-09479)

Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006–2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of –129 g (95% CI: –233, –25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (–248 g; 95% CI: –405, –92 g) compared with those with high intake (–58 g; 95% CI: –206, 90 g). Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective. ; The NewGeneris (Newborns and Genotoxic exposure risks) study was funded by the European Union (EU contract FOOD-CT-2005-016320). The study/nwas also supported by the National Institute for Health Research, United Kingdom (programme grant RP-PG-0407-10044), the Norwegian Ministry of/nHealth, the Norwegian Ministry of Education and Research, the Norwegian Research Council/FUGE (grant 151918/S10), the EU funded HiWATE (contract Food-CT-2006-036224), the U.S. National Institutes of Health (NIH)/National Institute of Environmental Health Sciences (contract NO-ES-75558), and the U.S. NIH/National Institute of Neurological Disorders and Stroke (grant 1 UO1 NS 047537-01). M.P. holds a Juan de la Cierva postdoctoral fellowship awarded from the Spanish Ministry of Science and Innovation (JCI-2011-09479)

Background: Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure–outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG–DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research. ; This work was supported by the European Union (EU) Integrated Project "Newborns and Genotoxic exposure risks; NewGeneris," 6th Framework Programme, Priority 5: Food Quality and Safety [FOOD-CT-2005-016320]. The study was also supported by grants obtained locally, including the National Institute for Health Research, UK (Programme grant RP-PG-0407-10044), the Norwegian Ministry of Health, the Norwegian Ministry of Education and Research, the Norwegian Research Council/FUGE (grant 151918/S10), and the EU-funded HiWATE (Health impacts of long-term exposure to disinfection by-products in drinking water; contract Food-CT-2006-036224)

Cervell; Investigació pediàtrica ; Cerebro; Investigación pediátrica ; Brain; Paediatric research ; Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term effects that GM-IVH have on hippocampal subfields, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old. All participants underwent a cognitive assessment and magnetic resonance imaging study. GM-IVH children evidenced lower scores in Full Intelligence Quotient and memory measures compared to their low-risk preterm and full-term peers. High-risk preterm children with GM-IVH evidenced significantly lower total hippocampal volumes bilaterally and hippocampal subfield volumes compared to both low-risk preterm and full-term groups. Finally, significant positive correlations between memory and hippocampal subfield volumes were only found in preterm participants together; memory and the right CA-field correlation remained significant after Bonferroni correction was applied (p = .002). In conclusion, memory alterations and both global and regional volumetric reductions in the hippocampus were found to be specifically related to a preterm sample with GM-IVH. Nevertheless, results also suggest that prematurity per se has a long-lasting impact on the association between the right CA-field volume and memory during childhood. ; This study was funded by the Spanish Ministry of Science, Innovation and Universities [P.I.: L. Zubiaurre-Elorza (PSI2017-83657-P)]. L. Fernández de Gamarra-Oca, S. Soria-Pastor, R. L. Zubiaurre-Elorza, and E. Solana hold fellowships from the Basque Government (PRE_2019_1_0105), the Spanish Ministry of Education and Science (AP2005-0047) and (AP2008-0935) and the Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona respectively. We would like to extend special thanks to the families and the children who participated in this study.

Genòmica; Comportament humà ; Genómica; Comportamiento humano ; Genomics; Human behaviour ; Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg|: 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg|: 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG. ; We very warmly thank all participants, their parents, and teachers for making this study possible. The project was supported by the "Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies" project (ACTION). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no 602768. Cohort-specific acknowledgements and funding information may be found in the Supplementary text.

Malaltia de Chagas; Dones embarassades llatinoamericanes; Salut maternoinfantil ; Enfermedad de Chagas; Mujeres embarazadas latinoamericanas; Salud maternoinfantil ; Chagas disease; Latin american pregnant women; Maternal and child health ; La malaltia de Chagas (MCH) continua sent un problema important de salut pública. L'OMS estima que en el món hi ha 8 milions de persones infectades per Trypanosoma cruzi, la majoria a l'Amèrica Llatina. En països no endèmics, com és el cas del nostre entorn, l'MCH s'observa en persones infectades que provenen de països endèmics o en infants nascuts en països no endèmics, però la mare dels quals ha estat infectada (transmissió congènita). A Catalunya, per tal de fer el control i la vigilància de l'MCH, l'any 2010 es va posar en marxa el Programa de prevenció i control de la malaltia de Chagas congènita a Catalunya, coordinat pel Departament de Salut i que inclou el diagnòstic, el control, el seguiment i el tractament de l'MCH congènita dirigits a les dones embarassades i als seus fills. En el marc del Programa, es va elaborar el Protocol de cribratge i diagnòstic de malaltia de Chagas en dones embarassades llatinoamericanes i en els seus fills, que es va editar el 2010. Aquest document va ser fruit de l'esforç conjunt de professionals sanitaris experts en la malaltia, de diferents societats científiques i de professionals del Departament de Salut de la Generalitat de Catalunya, amb el suport del Grup de Treball de Països No Endèmics i del Departament de Control de Malalties Tropicals Oblidades de l'OMS. El Protocol que es presenta, a més d'incloure les mateixes línies que la primera edició, disposa d'actualitzacions de diferents aspectes clínics, de diagnòstic i de vigilància epidemiològica basats en l'experiència i l'evidència observades durant aquests vuit anys del Programa de prevenció i control de la malaltia de Chagas congènita a Catalunya. Durant aquests darrers anys, s'ha reforçat la perspectiva de salut pública en el Programa, en el qual han participat un gran nombre de professionals de la xarxa assistencial i agents comunitaris de salut amb l'objectiu de reduir l'efecte de la transmissió vertical de l'MCH a Catalunya. La primera part del document recull les característiques clíniques de l'MCH que, encara que és d'aparició relativament recent en el nostre entorn, gràcies a la informació facilitada tant en l'àmbit sanitari com en l'àmbit comunitari durant els últims anys, ha deixat de ser una malaltia oblidada i desconeguda a Catalunya. En els darrers anys, els avenços i l'experiència en el nostre entorn en el diagnòstic de l'MCH ens han fet arribar a un consens sobre la utilització de mètodes directes moleculars, tal com es descriu en aquest Protocol. Així mateix, la concreció de dades epidemiològiques sobre prevalença d'infecció i incidència de casos de la malaltia ha millorat molt gràcies a la vigilància i notificació de dades recollides en el marc del Programa de prevenció i control de la malaltia de Chagas congènita a Catalunya pels professionals que formen part del Grup de Treball de la Malaltia de Chagas Congènita. En aquest aspecte i per tal de millorar-ne el control s'han incorporat els metges de família i salut comunitària, ja que són uns dels professionals clau que es troben més propers als pacients. Un aspecte fonamental que es desprèn d'aquest document i del funcionament del Programa és la multidisciplinarietat. El repte del sistema de salut i de la vigilància de la salut pública és la coordinació i el treball dels professionals de diferents àmbits sanitaris, com poden ser els ginecòlegs, els microbiòlegs, els llevadors, els pediatres d'atenció primària i hospitalària, els metges de família i salut comunitària, el personal d'infermeria, els infectòlegs, els epidemiòlegs i els agents de salut comunitària que treballen de manera conjunta per a l'assoliment de l'objectiu plantejat. El present Protocol constitueix un document eminentment pràctic, mitjançant el qual els professionals sanitaris disposen dels elements essencials per a la realització del cribratge en la dona embarassada. A partir d'aquest Protocol s'espera també aconseguir la detecció i el tractament precoç dels casos d'MCH en la població pediàtrica, nadons i altres fills a Catalunya, amb l'objectiu últim de millorar la salut maternoinfantil a Catalunya. ; La enfermedad de Chagas (ECH) sigue siendo un problema importante de salud pública. La OMS estima que en el mundo hay 8 millones de personas infectadas por Trypanosoma cruzi, la mayoría en América Latina. En países no endémicos, como es el caso de nuestro entorno, la ECH se observa en personas infectadas que provienen de países endémicos o en niños nacidos en países no endémicos, pero cuya madre ha sido infectada (transmisión congénita). En Cataluña, para hacer el control y la vigilancia de la ECH, en 2010 se puso en marcha el Programa de prevención y control de la enfermedad de Chagas congénita en Cataluña, coordinado por el Departamento de Salud y que incluye el diagnóstico, el control, el seguimiento y el tratamiento de la ECH congénita dirigidos a las mujeres embarazadas y a sus hijos. En el marco del Programa, se elaboró el Protocolo de cribado y diagnóstico de enfermedad de Chagas en mujeres embarazadas latinoamericanas y en sus hijos, que se editó en 2010. Este documento fue fruto del esfuerzo conjunto de profesionales sanitarios expertos en la enfermedad, de diferentes sociedades científicas y de profesionales del Departamento de Salud de la Generalidad de Cataluña, con el apoyo del Grupo de Trabajo de Países No Endémicos y del Departamento de Control de Enfermedades Tropicales Olvidadas de la OMS. El Protocolo que se presenta, además de incluir las mismas líneas que la primera edición, dispone de actualizaciones de diferentes aspectos clínicos, de diagnóstico y de vigilancia epidemiológica basados en la experiencia y la evidencia observadas durante estos ocho años del Programa de prevención y control de la enfermedad de Chagas congénita en Cataluña. Durante estos últimos años, se ha reforzado la perspectiva de salud pública en el Programa, en el que han participado un gran número de profesionales de la red asistencial y agentes comunitarios de salud con el objetivo de reducir el efecto de la transmisión vertical del ECH en Cataluña. La primera parte del documento recoge las características clínicas de la ECH que, aunque es de aparición relativamente reciente en nuestro entorno, gracias a la información facilitada tanto en el ámbito sanitario como en el ámbito comunitario durante los últimos años, ha dejado de ser una enfermedad olvidada y desconocida en Cataluña. En los últimos años, los avances y la experiencia en nuestro entorno en el diagnóstico de la ECH nos han hecho llegar a un consenso sobre la utilización de métodos directos moleculares, tal como se describe en el presente Protocolo. Asimismo, la concreción de datos epidemiológicos sobre prevalencia de infección e incidencia de casos de la enfermedad ha mejorado mucho gracias a la vigilancia y notificación de datos recogidos en el marco del Programa de prevención y control de la enfermedad de Chagas congénita en Cataluña por los profesionales que forman parte del Grupo de Trabajo de la Enfermedad de Chagas Congénita. En este aspecto y para mejorar su control se han incorporado los médicos de familia y salud comunitaria, ya que son unos de los profesionales clave que se encuentran más cercanos a los pacientes. Un aspecto fundamental que se desprende de este documento y del funcionamiento del Programa es la multidisciplinariedad. El reto del sistema de salud y de la vigilancia de la salud pública es la coordinación y el trabajo de los profesionales de diferentes ámbitos sanitarios, como pueden ser ginecólogos, microbiólogos, comadrones, pediatras de atención primaria y hospitalaria, médicos de familia y salud comunitaria, personal de enfermería, infectólogos, epidemiólogos y agentes de salud comunitaria que trabajan de manera conjunta para el logro del objetivo planteado. El presente Protocolo constituye un documento eminentemente práctico, mediante el cual los profesionales sanitarios disponen de los elementos esenciales para la realización del cribado en la mujer embarazada. A partir de este Protocolo se espera también conseguir la detección y el tratamiento precoz de los casos de ECH en la población pediátrica, bebés y otros hijos en Cataluña, con el objetivo último de mejorar la salud maternoinfantil en Cataluña. ; Chagas disease (CHD) continues to be a major public health problem. The WHO estimates that there are 8 million people in the world infected with Trypanosoma cruzi, the majority in Latin America. In non-endemic countries, as is the case in our environment, CHD is seen in infected people who come from endemic countries or children born in non-endemic countries, but whose mother has been infected (congenital transmission). In Catalonia, in order to control and monitor the CHD, in 2010 the Program for the Prevention and Control of Congenital Chagas' Disease in Catalonia was launched, coordinated by the Department of Health and includes diagnosis, control, follow-up and treatment of congenital CHD directed at pregnant women and their children. Within the framework of the Program, the Protocol for the Screening and Diagnosis of Chagas' Disease in Latin American pregnant women and their children was prepared, which was published in 2010. This document was the result of the joint effort of health professionals who are experts in the disease, of different scientific societies and professionals of the Department of Health of the Government of Catalonia, with the support of the Working Group of Non-endemic Countries and the Department of Control of Forgotten Tropical Diseases of WHO. The Protocol that is presented, in addition to including the same lines as the first edition, has updates on different clinical, diagnostic and epidemiological surveillance aspects based on the experience and evidence observed during these eight years of the Prevention and Control Program. Congenital Chagas disease in Catalonia. During these last years, the perspective of public health in the Program has been reinforced, in which a large number of professionals of the health care network and community health agents have participated with the aim of reducing the effect of the vertical transmission of CHD in Catalonia. The first part of the document includes the clinical characteristics of the CHD that, although it is relatively recent in our environment, thanks to the information provided both in the health field and in the community in recent years, has ceased to be a disease forgotten and unknown in Catalonia. In recent years, the advances and experience in our environment in the diagnosis of CHD have led us to reach a consensus on the use of direct molecular methods, as described in this Protocol. Likewise, the specification of epidemiological data on prevalence of infection and incidence of cases of the disease has improved greatly thanks to the monitoring and reporting of data collected within the framework of the Program for the Prevention and Control of Congenital Chagas' Disease in Catalonia by professionals. that are part of the Working Group on Congenital Chagas Disease. In this aspect and to improve their control, family doctors and community health have been incorporated, since they are one of the key professionals who are closest to patients. A fundamental aspect that emerges from this document and the operation of the Program is multidisciplinarity. The challenge of the health system and public health surveillance is the coordination and work of professionals from different health areas, such as gynecologists, microbiologists, midwives, pediatricians of primary and hospital care, family physicians and community health , nurses, infectious disease specialists, epidemiologists and community health workers who work together to achieve the stated objective. This Protocol is an eminently practical document, through which health professionals have the essential elements for carrying out screening in pregnant women. Based on this Protocol, it is also expected to achieve the detection and early treatment of cases of CHD in the pediatric population, babies and other children in Catalonia, with the ultimate goal of improving maternal and child health in Catalonia.