Suchergebnisse

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: The association between air pollution exposure and emotional and behavioural problems in children is unclear. We aimed to assess prenatal and postnatal exposure to several air pollutants and child's depressive and anxiety symptoms, and aggressive symptoms in children of 7–11 years. Methods: We analysed data of 13182 children from 8 European population-based birth cohorts. Concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM) with diameters of ≤10 μm (PM10), ≤ 2.5 μm (PM2.5), and between 10 and 2.5 μm (PMcoarse), the absorbance of PM2.5 filters (PM2.5abs), and polycyclic aromatic hydrocarbons (PAHs) were estimated at residential addresses of each participant. Depressive and anxiety symptoms and aggressive symptoms were assessed at 7–11 years of age using parent reported tests. Children were classified in borderline/clinical range or clinical range using validated cut offs. Region specific models were adjusted for various socio-economic and lifestyle characteristics and then combined using random effect meta-analysis. Multiple imputation and inverse probability weighting methods were applied to correct for potential attrition bias. Results: A total of 1896 (14.4%) children were classified as having depressive and anxiety symptoms in the borderline/clinical range, and 1778 (13.4%) as having aggressive symptoms in the borderline/clinical range. Overall, 1108 (8.4%) and 870 (6.6%) children were classified as having depressive and anxiety symptoms, and aggressive symptoms in the clinical range, respectively. Prenatal exposure to air pollution was not associated with depressive and anxiety symptoms in the borderline/clinical range (e.g. OR 1.02 [95%CI 0.95 to 1.10] per 10 μg/m3 higher NO2) nor with aggressive symptoms in the borderline/clinical range (e.g. OR 1.04 [95%CI 0.96 to 1.12] per 10 μg/m3 higher NO2). Similar results were observed for the symptoms in the clinical range, and for postnatal exposures to air pollution. Conclusions: Overall, our results suggest that prenatal and postnatal exposure to air pollution is not associated with depressive and anxiety symptoms or aggressive symptoms in children of 7 to 11 years old. ; ESCAPE Project. European Community's Seventh Framework Program (FP7/2007-2011-GA#211250). GENERATION R. The Generation R Study is conducted by the Erasmus 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 and Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The Generation R Study is supported by the Erasmus MC, 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. TNO received funding from the Netherlands Ministry of Infrastructure and the Environment to support exposure assessment. Generation R was supported by the European Union's Horizon 2020 research and innovation programme under grant agreement no 633595 (DynaHEALTH) and No. 733206 (LifeCycle). Henning Tiemeier received funding from the Netherlands Organization for Health Research and Development (NWO-grant 016.VICI.170.200). REPRO_PL. The REPRO_PL was mainly supported by the National Science Centre, Poland, under the grant DEC-2014/15/B/NZ7/00998, FP7 HEALS Grant N° 603946 and the Ministry of Science and Higher Education under grant agreement no. 3068/7.PR/2014/2. INMA. This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI04/1436, PI04/2018, PI05/1079, PI05/1052, PI06/1213, PI06/0867, PI07/0314, PI07/0252, PI08/1151, PI09/02647, PI09/02311, PS09/00090, PI11/02591, PI11/02038, PI13/02429, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/00118, PI17/00663, PI18/00909, and Miguel Servet-FEDER: MS13/00054, MS11/00178, MS16/00085, MSII16/00051, and CP18/00018), Generalitat de Catalunya-CIRIT 1999SGR 00241, La Fundació La Marató de TV3 (090430), Generalitat Valenciana (FISABIO-UGP 15-230, 15-244, and 15-249), Fundación Alicia Koplowitz, Department of Health of the Basque Government (2005111093 and 2009111069), Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), Obra Social Cajastur/Fundación Liberbank, Universidad de Oviedo, Consejería de Salud de la Junta de Andalucía (grant number 183/07), EU Commission (QLK4-1999-01422, QLK4-2002 00603, CONTAMED FP7-ENV-12502, and FP7-ENV-2011 cod 282957), and Fundación Roger Torné.

Importance: Air pollutants interact with estrogen nuclear receptors, but their effect on thyroid signaling is less clear. Thyroid function is of particular importance for pregnant women because of the thyroid's role in fetal brain development. Objective: To determine the short-term association of exposure to air pollution in the first trimester with thyroid function throughout pregnancy. Design, Setting, and Participants: In this cohort study, 9931 pregnant women from 4 European cohorts (the Amsterdam Born Children and Their Development Study, the Generation R Study, Infancia y Medio Ambiente, and Rhea) and 1 US cohort (Project Viva) with data on air pollution exposure and thyroid function during pregnancy were included. The recruitment period for the Amsterdam Born Children and Their Development Study was January 2003 to March 2004; for Generation R, April 2002 to January 2006; for Infancia y Medio Ambiente, November 2003 to January 2008; for Rhea, February 2007 to February 2008; and for Project Viva, April 1999 to November 2002. Statistical analyses were conducted from January 2018 to April 2019. Main Outcomes and Measures: Residential air pollution concentrations (ie, nitrogen oxide and particulate matter [PM]) during the first trimester of pregnancy were estimated using land-use regression and satellite-derived aerosol optical depth models. Free thyroxine, thyrotropin, and thyroid peroxidase antibody levels were measured across gestation. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of the cohort distribution with normal thyrotropin levels, following the American Thyroid Association guidelines. Results: Among 9931 participants, the mean (SD) age was 31.2 (4.8) years, 4853 (48.9%) had more than secondary educational levels, 5616 (56.6%) were nulliparous, 404 (4.2%) had hypothyroxinemia, and 506 (6.7%) tested positive for thyroid peroxidase antibodies. Concentrations of nitrogen dioxide and PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) were lower and had less variation in women in the US cohort than those in European cohorts. No associations of nitrogen oxide with thyroid function were found. Higher exposures to PM2.5 were associated with higher odds of hypothyroxinemia in pregnant women (odds ratio per 5-μg/m3 change, 1.21; 95% CI, 1.00-1.47). Although exposure to PM with an aerodynamic diameter of 10 μm or less was not significantly associated with hypothyroxinemia, the coefficient was similar to that for the association of PM2.5 with hypothyroxinemia (odds ratio per 10-μg/m3 change, 1.18; 95% CI, 0.93-1.48). Absorbances of PM2.5 and PM with aerodynamic diameter from 2.5 to 10 μg and were not associated with hypothyroxinemia. There was substantial heterogeneity among cohorts with respect to thyroid peroxidase antibodies (P for heterogeneity, <.001), showing associations of nitrogen oxide and PM with thyroid autoimmunity only in the women in the Generation R Study. Conclusions and Relevance: The findings of this study suggest that first-trimester exposures to PM2.5 were associated with mild thyroid dysfunction throughout pregnancy. The association of PM2.5 exposure with thyroid function during pregnancy is of global health importance because air pollution exposure is widespread and hypothyroxinemia may adversely influence the brain development of offspring. ; The Generation R Study was conducted by the Erasmus Medical Center in close collaboration with the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond, Rotterdam. Infancia y Medio Ambiente was funded by grants Red INMA G03/176 and CB06/02/0041 FIS-FEDER PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI042018, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/02311, PI09/02647, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI13/02429, PI14/00891, PI14/01687, PI16/1288, and PI17/00663, and Miguel Servet-FEDER CP11/00178, CP15/00025, MSII16/00051, MS13/00054, and CPII18/00018 from the Instituto de Salud Carlos III; grant CIRIT 1999SGR 00241 from the Generalitat de Catalunya; grants FISABIO UGP 15-230, UGP-15-244, and UGP-15-249 from the Generalitat Valenciana; grant 2005111093 from the Department of Health of the Basque Government; grant DFG06/002 from the Provincial Government of Gipuzkoa, annual agreements with the municipalities in the study area (Zumarraga, Urretxu, Legazpi, Azkoitia, Azpeitia, and Beasain); grants FP7/2007-2011-GA#211250, FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1 from the EU Commission; the Obra Social Cajastur and Fundación Liberbank; the Universidad de Oviedo; the Centro de Investigación Biomedica en Red Epidemiología y Salud Pública. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. The Rhea project was supported by European projects (EU FP6-2003-Food-3-A 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) and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece, 2011-2014). Project Viva was funded by grants R01 HD 034568, UH3 OD023286, K23 ES024803 from the National Institutes of Health.

Background: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. Participants and methods: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). Results: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. Conclusions: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG. ; The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement (grant number 669545; DevelopObese), the US National Institute of Health (R01 DK10324), Wellcome Trust (WT088806) and UK Medical Research Council (MC_UU_12013/4 and MC_UU_12013/5).

Introduction: Globally, mental illness affects social and occupational functioning. We aimed to highlight the barriers to employment experienced by persons with mental disabilities in Kenya and how they manage to find work against all the odds. Materials and Methods: Using a mixed-method study design, we purposely sampled persons with mental illness through networks of persons with psychosocial disabilities (Users and Survivors of Psychiatry and Africa Mental Health Foundation, Kenya). Qualitative data were obtained through in-depth interviews (n = 14) and four focus group discussions (n = 30), while a researcher-designed questionnaire was used to obtain quantitative data (n = 72). Results: We identified five major clusters of barriers to employment: mental illness factors, social exclusion and stigma, work identity crisis, non-accommodative environment, and socioeconomic status. Factors that facilitated employment include self-awareness and acceptance, self-employment, provision of reasonable accommodation, improved health services, addressing discriminatory laws and practices, and social development programs and support. Participants considered psychiatric illness the highest barrier to employment (63.2%), while supportive family/friends were considered the highest facilitator of employment (54.5%). Conclusion: The employment experiences of persons with mental disabilities are influenced by various interrelated factors in their social environment. Proactive social support and affirmative action by government may improve their employment opportunities and quality of life.

Background: Mental disorders affect employment and the ability to work, and mental healthcare providers are important in the promotion of health and employment for affected individuals. The objective of this study is to explore the perspectives of mental healthcare providers on pathways to improved employment for persons with mental disorders in two lower middle-income countries. Methods: Our study participants included mental healthcare providers (psychiatrists, occupational physicians, psychologists, and social care workers) from Kenya and Nigeria. Qualitative interviews and a focus group discussion were conducted with 15 professionals in Kenya and online questionnaires were completed by 80 professionals from Nigeria. Results: The study participants suggested that work is important for the recovery and wellbeing of persons with mental disorders. A complex interplay of factors related to the health of persons with mental disorders and the socioeconomic system in their setting were identified as barriers to their work ability and employment. Participants proposed four pathways to improved employment: including information on reducing stigma, better healthcare, policy advocacy in employment, and government commitment to healthcare and social welfare. Public education to reduce stigma and better healthcare were the highest reported facilitators of employment. Conclusions: Persons with mental disorders require multilevel support and care in obtaining and retaining employment. A better mental healthcare system is essential for the employment of persons with mental disorders.

Data de publicació electrònica: 11-01-2021 ; Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels. ; Study-specific funding information can be found in the Supplementary Methods. JR, AH, EL, and SS were supported by the European Union's Horizon 2020 research and innovation program [grant numbers 633595 (DynaHEALTH) and 733206 (LifeCycle)], Academy of Finland [grant number 285547 (EGEA)] and the Biocenter Oulu. ACJ was funded by the National Institute of Environmental Health Sciences [grant number R00ES023450]. AK was supported by the National Institute of Environmental Health Sciences [grant number R01ES021357]. DCa was funded by the UK Medical Research Council [grant number MC_UU_00011/7]. EKa received funding from the Horizon2020 grant for RECAP Research on Children and Adults Born Preterm [grant number 733280], Academy of Finland [grant number 315690], Foundation for Pediatric Research, Novo Nordisk Foundation, Signe and Ane Gyllenberg Foundation and Sigrid Jusélius Foundation. EKe received funding from the Finnish Medical Association. MG was supported by Miguel Servet fellowship from the Institute of Health Carlos III [grant numbers MS13/00054, CP18/00018]. MVä received funding from the Research Funds of Oulu University Hospital, Juho Vainio Foundation and Signe and Ane Gyllenberg Foundation. RCH was supported by the National Health and Medical Research Council Fellowship Grants [grant number 1053384]. SJL was supported by the intramural research program of the National Institutes of Health, National Institute of Environmental Health Sciences. SM received funding from the University of Oulu Graduate School. SR was supported by National Health and Medical Research Council EU [grant number 1142858] and the Department of Health, Western Australia FutureHealth fund in connection with the European Union's Horizon 2020 [grant number 733206].

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).

Background: Prenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD) and autistic traits in children produced mixed findings. Objective: The objective of the present study was to examine whether maternal urinary concentrations of OP pesticide metabolites are associated with ADHD and autistic traits in children participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. Method: Maternal concentrations of 6 dialkylphosphates (DAPs) were measured using gas chromatography coupled with tandem mass spectrometry in urine samples collected at 25 weeks of gestation in 784 mother-child pairs. DAP metabolite concentrations were expressed as molar concentrations divided by creatinine levels and log10 transformed. ADHD traits were measured at ages 3, 6, and 10 years using the Child Behavior Checklist (CBCL) (n = 781) and autistic traits were measured at age 6 years using the Social Responsiveness Scale (SRS) (n = 622). First, regression models were fit for the averaged prenatal exposure across pregnancy. Second, we investigated associations for each collection phase separately, and applied a mutually adjusted model in which the effect of prenatal DAP concentrations from each time period on ADHD and autistic traits were jointly estimated. All associations were adjusted for relevant confounders. Results: Median DAP metabolite concentration was 309 nmol/g creatinine at 25 weeks of gestation. Overall, DAP metabolite concentrations were not associated with ADHD traits. For instance, a log10 increase in averaged total DAP concentrations across gestation was not associated with a lower ADHD score (-0.03 per SD 95 CI: -0.28 to 0.23). Similarly, no associations between maternal DAP concentrations and autistic traits were detected. Conclusions: In this study of maternal urinary DAP metabolite concentrations during pregnancy, we did not observe associations with ADHD and autistic traits in children. These are important null observations because of the relatively high background DAP concentrations across pregnancy, the relatively large sample size, and the 10-year follow-up of the offspring. Given the measurement error inherent in our OP pesticide exposure biomarkers, future studies using more urine samples are needed to accurately measure OP pesticide exposure over pregnancy in relation to ADHD and autistic traits. ; This research received financial support from the National Institutes of Health Grants K12 ES019852 and P30 ES001247, and from the intramural research program of the National Institute of Environmental Health Sciences, National Institutes of Health. Henning Tiemeier was supported by a grant of the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development, and NWO/ZonMW grant 016.VICI.170.200). Mònica Guxens is funded by a Miguel Servet fellowship (MS13/00054, CPII18/00018) awarded by the Spanish Institute of Health Carlos III. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Dr. Hanan El Marroun was supported by Stichting Volksbond Rotterdam, the Dutch Brain Foundation (De Hersenstichting, project number GH2016.2.01) and the European Union's Horizon 2020 research and innovation programme (grant agreement No. 733206 LifeCycle).

BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility. OBJECTIVE: We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women. METHODS: We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log10-transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP). RESULTS: Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) [OR per log10-unit increase=1.99 (95% CI: 1.06, 3.78) and OR=1.65 ( 95% CI: 0.99, 2.76), respectively]. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels [percent median change per log10-unit increase=-5.86% (95% CI: -9.91%, -1.63%) and percent median change per log10-unit increase=-4.75% (95% CI: -8.16%, -0.61%, respectively], whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol [percent median change per log10-unit increase=1.26% (95% CI: 0.01%, 2.54%)]. PFASs were not associated with CRP in the subset of the population with available data (n=640). CONCLUSIONS: Although further confirmation is required, the findings from this study suggest that PFAS exposures during pregnancy may influence lipid metabolism and glucose tolerance and thus may impact the health of the mother and her child. https://doi.org/10.1289/EHP1062. ; This study was funded in part by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III, the Spanish Ministry of Health (Red INMA G03/176; CB06/02/0041; FIS-PI12/01890, FIS-PI041436, FIS- PI081151, FIS-PI06/0867, FIS-PS09/00090; FIS-FEDER: 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, 11/02038, 13/1944, 13/2032, 14/00891, and 14/01687; Miguel Servet-FEDER CP11/0178, MS13/00054, and CPII16/00051; and PFIS-FI14/00099), Generalitat Valenciana (FISABIO: UGP 15-230, UGP-15-244, and UGP-15-249), the Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), the Generalitat de Catalunya-CIRIT (1999SGR 00241), and the National Institutes of Health/National Institute of Environmental Health Sciences (grant number ES021477). This study has been reviewed and approved by the accredited committees of the following institutions: The Municipal Institute of Sanitary Assistance of Barcelona, La Fe University Hospital of Valencia, and The Donostia Hospital.

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: In 2003 the INMA-INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that children's environmental health research will face in the coming years. RESULTS: The INMA project has contributed to provide increasing evidence of the association between prenatal exposure to persistent organic pollutants (POPs) and child neuropsychological development, but it has also shown, using innovative methodologies, that postnatal exposure to these compounds does not play a role in this association. The project has also contributed to show the detrimental influence of certain air pollutants on child neuropsychological development, as well as how a balanced maternal fish intake can protect from the potential adverse effects of prenatal exposure to mercury. Also, the project has contributed to the understanding of impacts of nutritional factors including supplement intake and vitamin D levels during pregnancy and the role of breastfeeding on the neuropsychological benefits. CONCLUSIONS: INMA findings underscore the importance of continued research on the delineation of the sensitive windows of exposure both during pregnancy and postnatally and on the combined effects of environmental exposures, denoted the exposome. In terms of health policy, INMA findings have important implications for the development of public health policies to advance the health and development of children. ; This study was supported Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, 97/0588, 00/0021-2, PI04/1436, PI06/1756, PI08/1151, PS09/01958, PI12/01890, PI14/00677, MS13/00054, CP13/00054 including FIS-FEDER funds 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02311, 09/02647, 11/0178, 11/02591, 11/02038, 13/1944, 13/2032, 13/02429, 14/0891, 14/1687, and 16/1288) and Miguel Servet-FEDER MS15/00025, Spanish Ministry of Health - CIBERESP (FIS-97/1102, FIS-PS09/00362, FIS-07/0252, FIS-PI11/00610, FISPI07/0252, FISPI11/0610, FIS-PI04/2018, FIS-PI09/02311, FIS-PI13/02429, FIS-PI06/0867, FIS-PS09/00090, FIS-PI13/02187, PI13/02406, MS13/00054), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), EU Comission (QLK4-CT-2000-00263, QLK4-1999-01422, QLK4-2002-00603 and CONTAMED FP7-ENV-212502, FP7-ENV-2011 cod 282957, 261357, 308333 and 603794 and HEALTH.2010.2.4.5-1), Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR501, 2014 SGR 822), Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065), the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221), Consejería de Salud de la Junta de Andalucía (grant number 183/07 and SAS-PI-0675-2010), Conselleria de Sanitat, Generalitat Valenciana, Andalusia Regional Government – Consejería de Salud (Grants P09-CTS-5488 Project of Excellence, and SAS PI-0133-2007; PI-0675–2010), Agence Nationale de Securite Sanitaire de l'Alimentation de l'Environnement et du Travail (1262C0010), beca de la IV convocatoria de Ayudas a la Investigación en Enfermedades Neurodegenerativas de La Caixa, Fundació La Caixa (97/009-00 and 00/077-00), Fundació La Marató de TV3 (090430), Obra Social Cajastur/Fundación Liberbank and University of Oviedo, and annual agreements with the municipalities of the area of study (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain)

Background: Disinfection by-products (DBPs) constitute a complex mixture of prevalent chemicals in drinking water and there is evidence of neurotoxicity for some of them. Objectives: We evaluated the association between estimates of DBP exposure during pregnancy and child neuropsychological outcomes at 1 and 4–5 years of age. Methods: We conducted a population-based mother-child cohort study in Spain with recruitment at first trimester of gestation (INMA Project, 2003–2008). Neuropsychological development was measured at 1 year of age using the Bayley Scales of Infant Development and at 4–5 years with the McCarthy Scales of Children's Abilities. Modeled tap water concentrations of trihalomethanes (THM) were combined with personal ingestion, showering and bathing habits to estimate exposure as ingestion uptake, all route (showering, bathing, ingestion) uptake (μg/day) and crude levels (μg/l) in the residence. Chloroform, brominated THMs (bromodichloromethane, dibromochloromethane, bromoform) and total THMs (chloroform and brominated THMs) were analysed separately. Nine haloacetic acids levels were available in one of the areas. Linear regression was used to estimate associations in 1855 subjects adjusting for covariables. Results: The median concentration of total THMs, chloroform, brominated THMs, total haloacetic acids, dichloroacetic acid, and trichloroacetic acid were, respectively 30.3 μg/L, 9.4 μg/L, 11.6 μg/L, 10.5 μg/L, 2.7 μg/L, and 3.1 μg/L. The associations between THM exposure and neuropsychological outcomes were null, except for total and brominated THM uptake though all routes and the general cognitive score at 4–5 years, with a decrease in − 0.54 points (95%CI − 1.03, − 0.05) and − 0.64 (95%CI − 1.16, − 0.12), respectively, for doubling total and brominated THM uptake. A positive association found between dichloroacetic acid and the mental score at 1 year did not persist at 4–5 years. Conclusions: Minor associations observed between DBP exposure during gestation and child neuropsychological development at 1 year disappeared at 4–5 years. Although a suggestive association is identified for exposure to brominated THMs and the cognitive score at 4–5 years, chance cannot be ruled out. ; This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), and from Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, PI041436, FIS-PI042018, 05/1079, 05/1052, 06/1213, FIS-PI06/0867, 07/0314, 081151, 09/02647, 09/02311, 09/00090, 11/0178, 11/02591, 11/02038, 13/1944, 13/2032, 13/02429, 13/02187, 14/0891, 14/1687, CP14/00108, CP16/00261 and Miguel Servet-FEDER MS15/0025, MS13/00054, CP0610034, MS14/00108), CIBERESP (Ref. AA08_012), the Conselleria de Sanitat de la Generalitat Valenciana, Generalitat de Catalunya (CIRIT 1999SGR 00241), Fundació La Marató de TV3 (090430), Obra Social Cajastur/Fundación Liberbank, Universidad de Oviedo, 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). Annual agreements with the city council of the study area in Gipuzkoa (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.

Vitamin D deficiency during critical periods of development could lead to persistent brain alterations. We aimed to assess the association between maternal vitamin D3, the major circulatory form of vitamin D, at pregnancy and neurodevelopmental outcomes during childhood, namely: behavioural problems, Attention Deficit and Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) symptoms, and social competence. This study included 2,107 mother-child pairs of a Spanish population-based birth cohort. Maternal plasma vitamin D3 was measured in pregnancy. The outcomes were measured through questionnaires at 5, 8, 14, and 18 years old. We ran multivariate regression models adjusted for potential confounding variables. We found that per each 10 ng/mL increment of maternal vitamin D3, children obtained higher social competence scores (coefficient = 0.77; 95% CI = 0.19, 1.35) at 5 years old. However, we observed null associations between maternal vitamin D3 and total behavioural problems and ADHD and ASD symptoms in children from 5 to 18 years old. Further studies carried out in countries where the population is exposed to lower vitamin D levels are needed. ; We thank all the investigators who have collected information and samples from the participants. Menorca: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; 97/0588; 00/0021-2; PI061756; PS0901958; PI14/00677 incl. FEDER funds), CIBERESP, Beca de la IV convocatoria de Ayudas a la Investigación en Enfermedades Neurodegenerativas de La Caixa, and EC Contract No. QLK4-CT-2000-00263. 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; CPII/00018), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR 2009 SGR 501, Fundació La marató de TV3 (090430), EU Commission (261357). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Valencia: This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, and MSII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), and Alicia Koplowitz Foundation 2017. Asturias: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), FIS-PI042018, FIS-PI09/02311, FIS-PI13/02429, FIS-PI18/00909, CIBERESP, Obra Social Cajastur/Fundación Liberbank and UNIVERSIDAD DE OVIEDO. Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090 and FIS-PI13/02187), CIBERESP, 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).

Background: Air pollution effects on children's neurodevelopment have recently been suggested to occur most likely through the oxidative stress pathway. Objective: We aimed to assess whether prenatal exposure to residential air pollution is associated with impaired infant mental development, and whether antioxidant/detoxification factors modulate this association. Methods: In the Spanish INfancia y Medio Ambiente (INMA; Environment and Childhood) Project, 2,644 pregnant women were recruited during their first trimester. Nitrogen dioxide (NO2) and benzene were measured with passive samplers covering the study areas. Land use regression models were developed for each pollutant to predict average outdoor air pollution levels for the entire pregnancy at each residential address. Maternal diet was obtained at first trimester through a validated food frequency questionnaire. Around 14 months, infant mental development was assessed using Bayley Scales of Infant Development. Results: Among the 1,889 children included in the analysis, mean exposure during pregnancy was 29.0 μg/m3 for NO2 and 1.5 μg/m3 for benzene. Exposure to NO2 and benzene showed an inverse association with mental development, although not statistically significant, after adjusting for potential confounders [β (95% confidence interval) = –0.95 (–3.90, 1.89) and –1.57 (–3.69, 0.56), respectively, for a doubling of each compound]. Stronger inverse associations were estimated for both pollutants among infants whose mothers reported low intakes of fruits/vegetables during pregnancy [–4.13 (–7.06, –1.21) and –4.37 (–6.89, –1.86) for NO2 and benzene, respectively], with little evidence of associations in the high-intake group (interaction p-values of 0.073 and 0.047). Inverse associations were also stronger in non-breast-fed infants and infants with low maternal vitamin D, but effect estimates and interactions were not significant. Conclusions: Our findings suggest that prenatal exposure to residential air pollutants may adversely affect infant mental development, but potential effects may be limited to infants whose mothers report low antioxidant intakes. ; This study was funded by grants from the 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 (Consell Interdepartamental de Recerca i Innovació Tecnològica) (1999SGR 00241), Conselleria de Sanitat Generalitat Valenciana, Universidad de Oviedo, Obra social Cajastur, Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), and Fundación Roger Torné