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ANR funded project

Retour Post-Doctorants (RPDOC)
Edition 2012


PAPER


Pregnancy, Air Pollution, Epigenetics, and Respiratory health

Pregnancy, Air Pollution, Epigenetics and Respiratory health
The PAPER (Pregnancy, Air Pollution, Epigenetics and Respiratory health) project builds on the hypothesis that environmental exposures during the developmental period can influence foetal development and lead to programming of health in childhood and later on.

Impact of early-life exposure to highly prevalent and controllable environmental pollutants
Atmospheric pollution entails a major sanitary, social and economic burden in industrialised and non-industrialised countries. This is in particular the case for urban atmospheric pollution, which is composed of gases (nitrogen dioxide, NO2, carbon monoxide, CO, ozone, O3, organic volatile compounds such as benzene or polycyclic aromatic hydrocarbons…) and particulate matter (PM). There is a recognized need for improvement in tools to assess exposure to air pollutants.
In parallel, the field of epigenetic epidemiology is of particular interest for environmental health as demonstrated by recent studies, which showed that environmental exposures to air pollutants in adulthood could impact on epigenetic marks. Given that early pregnancy constitutes a period of intense epigenetic modeling, there is currently strong interest for studies linking early environmental exposures to pregnancy outcome and childhood health simultaneously considering epigenetic marks. The DOHaD (Developmental Origins of Health and Diseases) hypothesis focused on mid- and long-term health consequences of environmental exposures during the developmental period (foetal life and early childhood).
The aim of the PAPER project is to better characterize the impact of early-life exposure to highly prevalent and controllable environmental pollutants (gaseous atmospheric pollutants) on health on the short and mid-term, especially prenatal development and postnatal respiratory health.

A new type of birth cohorts with connected subjects
PAPER relies on the research platform formed by the couple-child SEPAGES (Suivi de l’Exposition à la Pollution Atmosphérique pendant la Grossesse et Effets sur la Santé) cohort, which is being recruited in Grenoble, France. Ethical agreements have been obtained from the relevant ethical committees (CPP (Comité de Protection des Personnes) Sud-Est, CCTIRS (Comité consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé)).
This new generation of birth cohorts correspond to an approach with early recruitment during pregnancy and connected subjects. By this, we mean repeated collection of data during pregnancy and the first years of life of the child with 1) detailed assessment of exposure using time-space activity measured by GPS, personal monitoring, and internet-based questionnaires, 2) repeated non-invasive clinical examinations, 3) and repeated biological samples collection to investigate biological pathways. In fact, a key innovation of SEPAGES is that exposure to air pollution will be assessed using sophisticated indicators allowing decreasing measurement error by combining space-time budget of the participants (GPS and questionnaires), concentrations in outdoor and indoor air (with monitoring devices), and breathing rate of the women (accelerometer). Ultrasound measures will be performed at each trimester of pregnancy providing a dynamic assessment of foetal growth. Lung function of the new-born will be measured at 2 months of age using flow-volumes curves measured during calm ventilation.

Results

The PAPER project connects environmental, reproductive, and respiratory epidemiology. It will address major public health issues, considering the very high prevalence of exposure to air pollution; the increasing prevalence of respiratory diseases; the vulnerable group formed by pregnant women and their foetus. The main strength of PAPER is the intensity of the follow-up and the accuracy of estimation of exposure and outcomes under study in a large-scale epidemiological study. The PAPER project will: a) provide an accurate estimate of gaseous air pollution exposure during pregnancy using innovative techniques including time-space budget of the women, allowing identification of exposure measurement error in cohort studies where such space time data is lacking b) identify the effects of maternal exposure to air pollution on foetal growth and lung function of the new-born c) collect several relevant biological samples that will be available for future projects aiming at elucidating the biological mechanisms underlying the associations between air pollutants and health, such as the role of DNA methylation.
Increasing knowledge on the health effects of air pollutants in so far little studied population (such as foetuses and pregnant women) would bring more incentives to stakeholders and citizens to enforce the current regulation and possibly define more stringent policies.

Outlook

From a disciplinary point of view, the PAPER project clearly moves beyond the borders of classical epidemiology, via a heavy reliance on most of sister disciplines of epidemiology such as biostatistics, biology, exposure sciences, non-invasive medical examinations, all fields with which strong bridges will be built. In terms of research field, many crucial issues of environmental health research will be tackled, including exposure measurement error, DOHaD, and mediation analysis to quantify the share of the possibly identified target functions and mechanisms in the effect of air pollutants.
The SEPAGES cohort will further offer valuable perspectives to undertake longitudinal studies investigating the pre- and post-natal effects of air pollution on lung function and neurodevelopment over time during childhood, as well as to explore pathways that may mediate the health effects of air pollution through cardiovascular mechanisms or genetic expression mechanisms (transcriptomic), using stored biological samples and clinical examinations during pregnancy.

Scientific outputs and patents

N/A

Partners

Inserm Inserm U823, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health

ANR grant: 480 000 euros
Beginning and duration: mars 2013 - 36 mois

Submission abstract

The DOHaD (Developmental Origins of Health and Diseases) hypothesis focused on mid- and long-term health consequences of environmental exposures during the developmental period (foetal life and early childhood). In this context, the PAPER (Pregnancy, Air Pollution, Epigenetics and Respiratory health) project aims to assess the effects of air pollution exposure during pregnancy on foetal growth and lung function of the newborn and will produce the following deliverables a) assess the effects of intra-uterine exposure to air pollution on foetal growth and lung function of the new-born b) identify novel pathways of air pollution effects on foetal growth and respiratory health through DNA methylation patterns.
PAPER relies on the couple-child SEPAGES (Suivi de l’Exposition à la Pollution Atmosphérique pendant la Grossesse et Effets sur la Santé) cohort, which will be recruited in Grenoble, France. Ethical agreements have been obtained from the relevant ethical committees (CPP (Comité de Protection des Personnes) Sud-Est, CCTIRS (Comité consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé)). A key innovation is that exposure to air pollution will be assessed using sophisticated indicators allowing decreasing measurement error by combining space-time budget of the participants (GPS and questionnaires), concentrations in outdoor and indoor air (personal monitoring devices), and breathing rate of the women (accelerometer). Ultrasound measures will be performed at each trimester of pregnancy providing a dynamic assessment of foetal growth. Lung function of the new-born will be measured at 2 months of age using flow-volumes curves measured during calm ventilation. Genome-wide DNA methylation will be measured in cord blood and pathway analyses will be conducted in association with air pollution exposure, foetal growth and lung function of the newborn. Mediation of air pollution effects through DNA methylation will be researched using counterfactual frameworks.
The PAPER project connects environmental, reproductive, respiratory and epigenetic epidemiology. It will address major public health issues, considering the very high prevalence of exposure to air pollution; the increasing prevalence of respiratory diseases; the vulnerable group formed by pregnant women and their foetus. The main strength of PAPER is the intensity of the follow-up, the accuracy of estimation of exposure and outcomes under study and the integration of epigenetic data in a large-scale epidemiological study. The SEPAGES cohort will further offer valuable perspectives to undertake longitudinal studies investigating the pre- and post-natal effects of air pollution on lung function and neurodevelopment over time during childhood, as well as to explore pathways that may mediate the health effects of air pollution through cardiovascular mechanisms or genetic expression mechanisms (transcriptomic), using stored biological samples and clinical examinations during pregnancy.
PAPER is in line with the project developed in the Inserm team of environmental Epidemiology applied to reproduction and respiratory health (U823) and relies on the research platform formed by the SEPAGES cohort. In the hosting team, the candidate will coordinate the air pollution program within SEPAGES and use her experience in epigenetics to develop this research field. She will benefit from collaborations with the Harvard school of Public Health established during her post-doc and from collaborations of the hosting team, which is strongly involved in national and European research networks.

 

ANR Programme: Retour Post-Doctorants (RPDOC) 2012

Project ID: ANR-12-PDOC-0029

Project coordinator:
Madame Johanna LEPEULE (Inserm U823, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health)
jlepeule@nullhsph.harvard.edu

 

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The project coordinator is the author of this abstract and is therefore responsible for the content of the summary. The ANR disclaims all responsibility in connection with its content.