Axis 4, Team 9 | Environmental exposure during pregnancy and infancy

Our aim is to understand and improve the assessment of environmental exposure during pregnancy and infancy; taking into account cumulative exposure to chemical and biological agents.
Populations are exposed to many different pollutants from a wide range of different sources, and via several channels (ingestion, inhalation, etc.), which makes it extremely difficult to assess their overall exposure levels. We use biological exposure markers to assess internal exposure, which includes all the possible sources. However, some types of environmentally-specific exposure, particularly in indoor environments, cannot currently be studied via individual biological measurements. Specific ways of exposure or source-based assessments constitute a complementary approach, especially for children, who can be particularly exposed to dust pollution, according to chemical product bioaccessibility. The overall quantitative measurement of exposure to biological agents (for example through moulds or bacteria in household dust) is rarely included in environmental epidemiological studies, with a view to assessing their role as specific risk factors or as effect modifiers interacting with chemical products.

Our NMR-based metabolomics research has shown that environmental exposure to agricultural pesticides among pregnant women is linked to specific metabolic footprint modifications in pregnant women's urine and in umbilical chord blood at birth. We are currently continuing our work in this field on a sample of 338 pregnant women from the PELAGIE cohort by developing an innovative approach enabling us to characterize pesticide exposure, using so called non-targeted metabolic profiling techniques to identify the relevant pesticide metabolites in urine, along with targeted techniques used to quantify these metabolites (the MULTIPEST Study). These data will be related to the previously identified metabolic footprint, enabling us to interpret their ability to predict exposure to agricultural pesticides. Building on the PELAGIE cohort year-12 follow-up data, this approach will be used to identify the effects of other types of environmental exposure on metabolic profiles at later stages in life.

In order to improve the assessment of exposure to environmental contaminants by ingestion, an easily-implemented sequential digestion method was developed to determine both the bioaccessible and total concentrations of metals in dust or in soils. It can be implemented in large scale deployments and allows improved assessment of cadmium, lead and arsenic exposure. Work is currently being undertaken using this approach, to measure organic contaminant bioaccessibility in household dust (the CHARAD study), in order to better take into account the effect of the bioavailability of toxic substances on reproduction and child development, particularly in indoor environments.

In order to better assess the health risks for children exposed to semi-volatile organic compounds (including those present in flame-retardants, plastifying agents, pesticides, etc.), we are developing an aggregate exposure assessment approach including three different ways of exposure, i.e. inhalation, dust ingestion and skin contact with ambient air. Risk is assessed on the basis of the effects and active mechanisms common to the different compounds, irrespective of their chemical families, while taking into account their relative toxicity according to standardised experimental data (the ECOS-Habitat study). Moreover, in order to take into account recent changes in the use of indoor chemical substances, exposure and risk assessments are broadened to include the new class of organophosphorous flame-retardants. A study assessing exposure to these compounds and their possible health effects, particularly in the cognitive field; will be implemented under the ELFE national mother-child cohort study (the ENFLAM study).

To date, the assessment of environmental biological contamination was mainly based on culture-based, biochemical or molecular analyses linked to specific biological agents thought to be responsible for health effects on children. We are developing an integrative approach based on an overall high throughput sequencing test for 16S genes (bacteria) and 18S genes (organisms such as moulds) in household dust samples obtained by vacuum collection, at different ages (6 and 12) of the children living in those dwellings. This approach will allow us to develop a compound environmental index which reflects the overall indoor environmental biological exposure risk for infants and children. The index could be combined with chemical exposure data, for use in epidemiological studies. As our microbial environment is strongly influenced by our own microbiome, we are also collecting saliva samples from children aged 12 to determine the links between environmental contaminants in dust and biological contaminants in saliva, using a similar methodology.