Asset Publisher

Epigenetics in the early life exposure to air pollution and neurodevelopment and behaviour disorders within families in the INMA Sabadell birth cohort (SIBLINGS). PROYECTO INMA

01/01/2013 ? 31/12/2015
Jordi Sunyer Deu
Funded by
Exposure to indoor and outdoor air pollution during susceptibility windows of the developmental period may result in white matter lesions and vascular pathology in brain areas that could be the basis for cognitive deficits and behavioural impairment later in life. Animal studies have demonstrated that these lesions are related to either deposition of ultrafine particles (UFP) containing metals in the olfactory bulb or in frontal cortical and subcortical areas, or alternatively to the neuroinflammation process that follows the inflammatory systemic responses secondary to oxidative stress triggered by air pollutants. Epidemiological research on neurodevelopment is recent and limited and there is need for large studies assessing the development of the global mental function and its specific areas, as well as on the clinical impact in social impairment and attention-deficit hyperactivity disorder (ADHD) by performing prospective assessment of environmental exposures during early life phases. According to recent studies, adverse effects of air pollution and inflammation are probably mediated by epigenetic changes that alter gene expression. However, studies on epigenetic changes are small, scarce and none related to adverse neurological effects. Besides, the INMA birth cohort provides an opportunity given the prospective design in collecting information on exposures at birth and early life, and the study of siblings with discordant information on exposures within families providing a perfect control of cofactors. The INMA project is a set of birth cohorts that aims to asses the role of early-life environment on children development and health in different areas of Spain. We have reported both indoor (i.e., use of gas cooking and maternal smoking) and outdoor air pollution to be determinants of cognitive impairment and ADHD symptoms. These adverse effects are probably due to the neurotoxic effect of ultrafine particles that may be mediated through changes in epigenetic marks. However, the potential for residual confounding for variables related with social class or genetics could not be discarded. A way of controlling for these effects is the conduction of sibling studies. The tremendous amounts of information that can be obtained from examining health outcomes within the context of the family have great potential. The present project aims to recruit all the siblings (around 600 sibling from a total of 1000) of the participants in the INMA-Sabadell cohort. The objectives are: 1. To asses the association of prenatal and early life exposure to air pollution with neurodevelopment and behaviour disorders within sibling pairs 2. To asses the effects of prenatal exposure to air pollution on epigenetic marks, in terms of DNA methylation changes, by using/comparing sibling pairs 3. To asses the intermediate role of DNA methylation changes on the association between air pollution and neurodevelopment and behaviour disorders. The plan is to exam within each family the sibling(s) of the INMA children, in order to avoid the role of factors that are constant within the family, using the same tools and devices used for the ‘probands’. Individual exposure estimates of outdoor in air pollution (particles, nitrogen dioxide, and volatile organic compounds) during pregnancy and at birth will be obtained, as well as other exposures such as indoor combustion sources and maternal smoking for both siblings. 2 The outcomes that will be examined in each sibling are the cognitive function (through validated psychometric tools performed by psychologists, either the Bayley, McCarthy or WISC upon the age), standardised computer assisted tests on executive function and attention, as well as a short questionnaire to the parents on the clinical history and environmental exposures during each pregnancy and early life of each sibling as well as record linkage with clinical records during pregnancy. Changes in DNA methylation will be assessed using the HumanMethylation450 (Illumina) chip assayed in DNA samples of the discordant siblings (around 400 children from 200 pairs). Results could contribute to the understanding of the causal links between environmental exposures and neurological impairment in children which is expected to be translated in the following aspects: 1. could have a direct application on implementation of environmental policies both at home and urban air level for improving children health 2. will expand the epidemiological knowledge of ADHD and other neurodevelopment variables 3. will provide evidences for the extension of this type of design in the rest of cohorts in the INMA study in Spain and also to other birth cohorts in Europe. 4. The identification of epigenetic marks associated with ADHD and other neurodevelopment variables in childhood could provide more insight into the complex pathophysiology of mental disorders and help develop early interventions to prevent these diseases. Communication to the participants and the general population of the results, beyond the research community is a mandate for the INMA researchers. Dissemination actions are carried out through: 1) direct communication with the main participants and professionals involved in the Sabadell cohort, including parents, doctors and nurses, schools, and the city council 2) communication with the main professional bodies responsible for developing prevention programs 3) dissemination to the scientific community 4) dissemination to general population through 

Our Team

Principal Investigator (PI)

Our Team

  • Raquel Garcia Esteban
    Raquel Garcia Esteban
  • ID#malvarez#

Other projects

See Past Projects


Population based multicasecontrol study on common tumours in Spain


Novel tools for integrating early-life environmental exposures and child health across Europe


Early Genetics Growth/Early Genetics and Lifecourse Epidemiology


Pregnancy and Childhood Epigenetics


Early-life stressors and LifeCycle health


Network on the Coordination and Harmonisation of European Occupational Cohorts


Health effects of cArdiac fluoRoscopy and mOdern radIotherapy in paediatriCs


Connecting digital mobility assessment to clinical outcomes for regulatory and clinical endorsement


Signs of Early Adaptation to Climate Change


Cohorte Covid-19 en Cataluña


Advancing Tools for Human Early Lifecourse Exposome Research and Translation


Cohort of COVID-19 in Spain: social dynamics, mental health and inequalities


A federated FAIR platform enabling large-scale analysis of high-value cohort data connecting Europe and Canada in personalized health


An integrative strategy of testing systems for identification of EDs related to metabolic disorders


EXposome Powered tools for healthy living in urbAN SEttings


Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics


Fine Particle Matter, Fetal Growth, and Neurodevelopment: Examining Critical Windows of Susceptibility


Pre-natal exposure to urban AIR pollution and pre- and post-Natal Brain development


The role of seafood and nut consumption on human neurodevelopment from pregnancy to adolescence


Urban and social environment and childhood obesity – a natural moving2health experiment


In-Depth Genomics and Cross-Omics Analysis for Undiagnosed Rare Diseases on a User-Friendly Collaborative Platform


An Exposome Approach to Urban Health: Individualized Environmental Exposure Assessment in an Adults Population Cohort Study (GCAT)


Digital Twins Enabled Indoor Air Quality Management for Healthy Living


The Urban Burden of Disease Estimation for POLICY Making


Combining Artificial Intelligence and smart sensing TOward better management and improved quality of LIFE in chronic obstructive pulmonary disease


Drinking Water in Barcelona: Sustainability and Health Impact Assessment


Innovative Tools to Control Organic Matter and Disinfection Byproducts in Drinking Water


FTIR spectroscopy for real-time detection of bacterial outbreaks and the rapid identification of pathogenic serotypes, relapsing infections and antibiotic resistance


Occupational exposure to radiofrequency electromagnetic fields: From exposure assessment to study of health in workers and their offspring


Exposome Project for Health and Occupational Research


Analysing and studying how night shift work affects workers' circadian rhythms and health


International Human Exposome Network


Una prueba en el punto de atención para la estratificación del riesgo de los pacientes febriles basada en los niveles de sTREM-1


e-health tools to promote Equality in Quality of Life for childhood to young adulthood cancer patients, survivors and their families