Current projects

Project investigator: Valérie Siroux and Gaëlle Uzu
Location of the projet: Inserm U1209; IRD Umr 252
Funding sources: PHD grant from ADEME-ANSES (ADEME); CDP IDEX UGA MOBILAIR (ANR-15-IDEX-02) ; ANR (GetOPstandOP ANR-19-CE34-0002) ; CDP CDTOOLS IDEX UGA ACME

The project addresses the general issue of the health impact associated with exposure to particulate matters, specifically focusing on the validation of the oxidative potential (OP) of particulate matter (PM) as a relevant indicator to quantify the health effects of exposure to PM. This thesis work is structured around the following specific objectives:

• 1) Estimate the population's exposure to the oxidative potential of aerosols in a medium-sized city and characterize its spatiotemporal variability. This aspect relies in part on indoor and outdoor air samples collected between 2018-2019 from families in the SEPAGES cohort, funded by MobilAir;
• 2) Characterize the associations between OP measurements and objective health measures and immune markers in the SEPAGES cohorte. These associations will be compared with those obtained for the current regulatory metric (mass concentration of particles).
• 3) Characterize the associations between OP measurements and biomarkers of oxidative stress.

Project investigator: Johanna Lepeule
Location of the projet: Inserm U1209
Funding sources: No funding

Maternal air pollution exposure during pregnancy has been associated with adverse birth outcomes. Epigenetic modifications could be one of the gene-regulatory mechanisms underlying these associations. Little is known about the effect of maternal air pollution exposure on placental epigenetic aging. The objective of this project is to build a placental epigenetic clock and investigate the relationship of NO2, PM10 and PM2.5 exposure during pregnancy with placental epigenetic aging.

Project investigator: Johanna Lepeule
Location of the projet: Inserm U1209
Funding sources: ANR ETAPE (No. ANR-18-CE36-0005)

The project is based on two mother-child cohorts (SEPAGES and EDEN) with longitudinal data including prenatal and postnatal exposures, placental methylation, and repeated assessments of health events. "Poly-mediator" models will be developed to identify all mediators and characterize the direct and indirect roles of these mediators in the associations between exposure and health events. Latent variable methods will be used to specify causal factors and confounding factors, thus providing a better understanding of the relationship between exposure/event and high-dimensional mediators. The project objectives are as follows:

• 1) To study the links between air pollution exposure and placental methylation in SEPAGES and EDEN cohorts;
• 2) To study the links between placental methylation in SEPAGES and pulmonary function at 2 months and 3 years;
• 3) To evaluate the effects of air pollutants on behavior and cognitive function mediated by placental methylation in SEPAGES and EDEN cohorts;
• 4) To assess the effects of air pollutants on pulmonary function mediated by placental methylation in SEPAGES cohort.

Project investigator: Johanna Lepeule and Mathilde Pascal
Location of the projet: Inserm U1209, Santé Publique France
Funding sources: Santé Publique France

An increasing number of studies suggest an effect of heat on prematurity, low birth weight and stillbirth. There are possible modifying or mediating effects between temperatures and other environmental and socioeconomic risk factors. The presence of urban heat islands, exposure to air pollution, or low socioeconomic status may simultaneously exacerbate heat exposure, physiological susceptibility to heat, and individual adaptation capacity and thus influence the relationship between temperatures and perinatal health. The different degrees of exposure to these factors can hide social and territorial inequalities that cause ecological inequalities. Conversely, urban vegetation is a potentially protective factor, likely to limit exposure to other risk factors (heat, pollution), while promoting health-promoting behaviors (physical activity, social contacts, psychological well-being). The research objectives are to:

• 1) identify temporal windows of heat sensitivity during pregnancy;
• 2) quantify their effects on prematurity and birth weight in 4 mother-child cohorts, considering the modifying or mediating effect of environmental co-exposures and socioeconomic factors;
• 3) study the association between high temperature exposures during pregnancy and accelerated epigenetic placental aging.

Project investigator: Johanna Lepeule and Claire Philippat
Location of the projet: Inserm U1209
Funding sources: Inserm recurring allocation

Maternal thyroxine (T4) and triiodothyronine (T3) have been demonstrated to be crucial for fetal growth, development, and maturation as well as embryogenesis. Uncontrolled maternal hypothyroidism can negatively affect fetal growth, birth outcomes, children's development, as well as other pregnancy-related issues. To promote proper fetal growth throughout pregnancy, maternal thyroid hormones pass through the placenta, amniotic fluid, and umbilical cord to the fetus. In early pregnancy the fetus is most dependent on the mother's thyroid hormones, making it crucial to maintain normal levels for the fetus' growth, metabolism, and development. To prevent unfavorable pregnancy and delivery outcomes caused by alterations in thyroid hormones, it is crucial to identify factors that can change maternal thyroid hormone levels throughout the early stages of pregnancy. The research objective is to study the influence of air pollution (NO2, PM2.5, benzene, toluene, ethylbenzene, and xylenes) on thyroid hormones (free and total T3, free and total T4, ratio of T3 and T4, TSH) during pregnancy.

Project investigator: Marion Ouidir
Location of the projet: Inserm U1209
Funding sources: National Research Agency (PEACH Project No. ANR-24-CE36-5914-01)

Previous studies have shown associations between birth weight and exposure to air pollutants during pregnancy. However, studies investigating the associations between these prenatal exposures and the future health of children are less common. Given the increasing prevalence of cardiovascular diseases in children and adolescents, identifying early and modifiable risk factors is a significant public health concern. So far, most studies examining the effects of air pollution on health have used ambient models based on residential address, without considering an individual's daily activities or indoor air quality. This approach can introduce biases in the dose-response relationship and compromise the precision of estimating this relationship. To further our understanding of environmental impacts and how the placenta can mediate the future health of children, some studies have focused on placental epigenetics as a potential candidate mechanism to explain the effects of the broader environment on fetal development and future child and adult health. The majority of molecular-scale studies on the placenta have explored epigenomics, particularly DNA methylation, as a proxy for gene expression to explain a phenotype. However, other mechanisms are involved in the reversible modification of gene expression (e.g., acetylation). Direct analysis of transcriptomic allows us to overcome the various mechanisms that modify gene expression by quantifying transcript expression levels. The objective of this project is to investigate the potential mediating role of placental gene expression (transcript expression levels) in the associations between prenatal exposure to air pollutants and the genesis of cardiovascular diseases in later life.

Project investigator: Peter D Sly AO
Location of the projet: Queensland Children’s Hospital, Australia
Funding sources: European Respiratory Society

The ERS CRC INCIRCLE was formed with the aim of improving assessment of lung function in young children, primarily through improving and validating intra-breath oscillometry for use in young children. A substantial amount of data has been collected in healthy young children and in those with various respiratory conditions, including in the SEPAGES cohort. We now propose to combine data collected in different parts of the world to create a normative data set for IB-OSC outcome variables. Most data have been collected with INCIRCLE wave-tube equipment and analysed using ad hoc software. A few data sets have been collected with TremoFlo or pneumotach-based equipment. The research objectives were:

• 1) To develop normative equations for IB-OSC outcome variables in children, to create Z-scores, where appropriate, and to investigate factors influencing lung function in healthy children;
• 2) To determine whether data collected with commercial or other pneumotach-based) equipment is equivalent to those collected with INCIRCLE equipment;
• 3) To use the normative data to examine changes in children with various respiratory conditions;
• 4) To make the normative data available in the GLI data set.

Project investigator: Marion Ouidir
Location of the projet: Inserm U1209
Funding sources: APMC (Project Dyscard)

Blood lipid levels, such as total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, undergo significant changes during pregnancy to support its maintenance and ensure fetal development. Epidemiological studies have shown an association between abnormal blood lipid levels, known as dyslipidemia, during pregnancy and an increased risk of cardiovascular events in adulthood. Blood pressure, commonly measured in adults, is rarely assessed in children due to its high variability. Repeated blood pressure measurements throughout early childhood can provide a better characterization of children's cardiovascular health. Furthermore, direct examination of microcirculation would offer a more comprehensive insight into children's cardiovascular health. The eye's fundus is the only part of the body where microcirculation can be directly evaluated. Analysis of retinal vessels serves as a promising surrogate vascular biomarker for the long-term assessment of cardiovascular risk, including hypertension, coronary artery diseases, and cardiovascular mortality. Studying retinal microcirculation in pediatric studies could yield new insights into the origins of cardiovascular diseases in their very early stages. The primary objective of the project is to investigate whether maternal blood lipid concentrations are associated with the cardiovascular health of children, as assessed through repeated blood pressure measurements during childhood and changes in retinal microcirculation at the age of 8. Secondary objectives include:

• 1) Identifying whether changes in child blood lipid concentrations explain part of the link between maternal dyslipidemia and the cardiovascular health of the child;
• 2) Describing the children's blood pressure trajectories up to the age of 8;
• 3) Investigating the direct link between children's blood pressure from early infancy to 8 years of age and the retinal microcirculation of the children at 8 years.

Project investigator: Sabine Plancoulaine
Location of the projet: Inserm U1153
Funding sources: Doctoral scholarship

The arrival of a child in a family disturbs the life habits and in particular the sleep of the parents. Studies on the sleep of new parents focus mainly on the mother's sleep, and on the first months of life, showing a decrease in the quality and quantity of sleep, in postpartum mothers, generally linked to symptoms of depression. The research objectives are:

• 1) to describe the sleep characteristics (quality and quantity) of the new parents (father and mother) between birth and 3 years and their changes over time, based on questionnaires; to identify early associated factors with a focus on parents’ chronotypes and child’s birth rank; to study the interrelations between the new fathers and mothers sleep characteristics over time;
• 2) to describe the child sleep characteristics between birth and 3 years and their changes over time, based on questionnaires and accelerometer data; to identify early associated factors with a focus on parents’ chronotypes;
• 3) to study the interrelationships between both parents’ and their child sleep characteristics over time.

Project investigator: Liesbeth Duijts
Location of the projet: Erasmus Medical Center Rotterdam
Funding sources: European Union’s Horizon 2020 research and innovation program (ATHLETE Project N° 874583)

It is already known that several early-life risk factors play a role in the development of childhood diseases. However, the interplay between these factors is not fully understood. Therefore the aim of this project is to develop a prediction model on meta-analysis level based on novel risk factors and protective factors to predict a personalized risk on the development of respiratory outcomes in childhood. Potential risk factor groups include parental factors of atopy, maternal factors during pregnancy, birth characteristics, infant to pre-school anthropometrics and disease history.

Project investigator: Judith van der Waerden
Location of the projet: Department of Social Epidemiology (ERES) | Inserm U1136
Funding sources: Doctoral scholarship

Environmental stressors during childhood are established to influence certain aspects of psychological, behavioural, and socioemotional development. However, the impact of paternal mental illness remains understudied. Global data suggests that approximately 5-10% of fathers are susceptible to depression in the perinatal period (both pre- and post-partum), with rates of perinatal anxiety also ranging 3.4%-25.0% prenatally and 2.4%-51.0% postnatally. With changing family dynamics and increased paternity leave across Europe, fathers are arguably playing a more active role in child rearing now more than ever. Indeed, paternal mental illness has been shown to negatively impact child development from infancy to late adolescence, resulting in behavioural and emotional problems in children, as well as subsequent psychological problems such as depression, substance abuse, and suicidal behaviour. However, certain domains have not yet been investigated, particularly so in relation to neurodevelopmental disorders in a French context. Moreover, the effect of father’s mental health on their children has also been seen to act independently of mothers’ psychopathology, with the presence of paternal depression shown even to aggravate the negative effects of maternal depression on child development. Improved understanding of the relationship between fathers’ mental illness and their child’s development will enable social and health care services to better target, support and prevent developmental impairment in children most at risk. With the data from Sepages, the aim is to investigate the link between paternal mental illness and child psychological, behavioural, and socioemotional development. As the population of the SEPAGES cohort has been shown to be unrepresentative of the French national population, these associations will be further examined in relation to various environmental and socioeconomic factors.