Author: Michelle Leemans, Alan Ricardo Patlan Hernandez & Bénédicte Jacquemin
The REMEDIA project takes a three-pronged approach that involves data integration, experimental work, and computational analyses. To achieve data integration, the project leverages six carefully selected existing cohorts and population registries. One of these is the Pélagie cohort, which serves as an excellent example of REMEDIA’s approach.
Presentation of the Pélagie cohort
Pélagie (Perturbateurs Endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l’Infertilité et l’Enfance (Endocrine Disruptors: Longitudinal Study of Pregnancy, Infertility and Childhood Abnormalities), is a mother-child cohort carried out since 2002 in Brittany, France. Pélagie aims to assess the effects of environmental and occupational exposures on children’s health. Specifically, the study focuses on prenatal exposure to solvents, pesticides, persistent organic pollutants, and chlorination byproducts and their impact on pregnancy, perinatal outcomes, and child development. Pélagie also aims to identify the sources and determinants of exposure, as measured by biomarkers, and to investigate the individual impacts of prenatal and childhood exposures. Moreover, with this cohort, researchers aim to better understand the complex interplay between environmental and lifestyle factors, socio-demographic characteristics, genetic susceptibility, and their potential influence on child health.
Pélagie recruited pregnant women in their first trimester of pregnancy (<19 weeks of gestation) who resided in the Brittany region, France, from 2002 to 2005. 3,421 participants from more than 40 different health centers were included during prenatal care visits to gynecologists, obstetricians, midwives, or ultra-sonographers. This prospective cohort follows-up individuals from birth all the way up to early adulthood. Children have participated in 3 follow-ups after birth; one at 2 years old (2004 to 2008), one at 6 years old (2008 to 2012), and finally at 12 years old (2015 to 2022). A fourth follow-up at 18-19 years old has started during the last quarter of 2022 and is ongoing.
The PELAGIE database integrates various types of data, including clinical examination, self-reported, and biological data. Self-reported data is collected through validated self-administered questionnaires, gathering information on the child’s immediate environment (indoor and outdoor), family health history, child’s health and development outcomes, etc. Clinical data was collected through medical examinations at birth for all included participants, and at 12-years follow-up for a sub-sample of 559 children.
Pélagie collected samples from several biological matrices: umbilical cord blood, placenta, child’s saliva and blood, and urine and hair from the children and their mothers. These samples have enabled the measurement of several exposure biomarkers such as persistent organic pollutants, heavy metals, and pesticides.
In order to generate all these data, Pélagie is conducted by a research team from the INSERM (National Institute of Health and Medical Research) at the Institut de recherche en santé, environnement et travail (Irset). It additionally counts with several active partners involved in the clinical examinations and the biological matrices sampling or analysis, such as the Rennes University Hospital, maternity wards, obstetricians, pediatricians, the Institut national de santé publique du Québec (INSPQ), among others.
Selected Pélagie sub-studies
- PEPSY: PElagie and the monitoring of neuroPSYchological development – A subgroup of 287 children was randomly selected from the Pélagie cohort for further follow-up of cognitive and psychological development around the age of 6 years, and the assessment of brain function by medical imaging around the age of 10-12 years, in addition to the assessment of the environment in which they evolve.
- “Grandir et changer” (“Growing-up and changing”): Another subgroup of about 1600 children was selected for follow-up of pubertal development from 9 to 16 years of age through annual auto-questionnaires for both, the child and their parents, plus an annual clinical examination carried out by a physician.
PÉLAGIE & REMEDIA
Exposure to ambient air pollution is a widespread and significant threat to the developing fetus and early postnatal life, as established by multiple studies 1–3. These vulnerable populations are particularly susceptible to environmental pollutants due to their physiological immaturity 4, and such exposure can result in long-lasting health consequences throughout their lives. The REMEDIA project includes the Pélagie cohort with the objective of investigating the potential link between early-life environmental exposures such as air pollution and greenspaces, and their effects on respiratory health outcomes.
The REMEDIA project seeks to enrich the existing database by integrating publicly available environmental and contextual information, matched with subjects’ geocoded residences. Alongside this, epigenetic pattern changes will be investigated within the Pélagie cohort. Epigenetic changes refer to modifications in gene expression that occur without any changes in the underlying DNA sequence. These modifications can impact gene function, leading to alterations in development and disease susceptibility. Epigenetic changes are mediated by a range of mechanisms, including DNA methylation, and can be influenced by various factors such as aging, diet, stress, and toxin exposure, including air pollution. As part of the REMEDIA project, we will conduct a longitudinal study to investigate how environmental exposures affect health outcomes over time. For this, DNA methylation analysis will be carried out on cord blood at birth and peripheral blood samples at age 12 from the same participants in the Pélagie study. By analyzing DNA methylation patterns in response to environmental exposures, we aim to identify potential biomarkers of exposure and understand the underlying biological mechanisms linking environmental exposures to health outcomes. Additionally, descriptive analyses and unsupervised clustering approaches will be utilized to effectively characterize exposure profiles.
Overall, Pélagie is a valuable resource for researchers interested in exploring the impact of environmental and professional exposures – including prenatal – on child development. The study’s multidisciplinary approach and extensive data collection provide a unique opportunity to investigate the complex interplay between environmental factors and child health.
- Stapleton, A. et al. Associations between pre-and postnatal exposure to air pollution and lung health in children and assessment of CC16 as a potential mediator. Environ. Res. 204, 111900 (2022).
- Ni, Y. et al. Associations of Pre- and Postnatal Air Pollution Exposures with Child Behavioral Problems and Cognitive Performance: A U.S. Multi-Cohort Study. Environ. Health Perspect. 130, 067008 (2022).
- Sunyer, J. & Dadvand, P. Pre‐natal brain development as a target for urban air pollution. Basic Clin. Pharmacol. Toxicol. 125, 81–88 (2019).
- Hackley, B., Feinstein, A. & Dixon, J. Air Pollution: Impact on Maternal and Perinatal Health. J. Midwifery Womens Health 52, 435–443 (2007).