Pre- and postnatal co-exposure to a wide range of dietary contaminants and child growth and development – COCTELL

This project was possible thanks to several data available before its start. Indeed, the data from the two large birth cohorts EDEN and Elfe were essential. During the follow-up, many data have been collected allowing to assess child health status as well as many variables to take into account as confounders in the statistical analyses. Furthermore, we also had in these cohorts, food frequency questionnaires essential here to assess the exposure.
The second key element to assess the exposure in the project COCTELL is the measure of contaminants in the foodstuffs in France and these national total diet studies are coordinated by ANSES.
Exposure assessment of one mother to one contaminant is given by doing, for each food or group of foods, the product between food consumption and the measure of the contaminant in this food item, then by summing the results over all the food items.
Finally, novel statistical tools are used in this project, in particular methods allowing to identify mixtures of contaminants in the population (NMU method: « non-negative matrix underapproximation ») and to create groups of mothers sharing the same exposure profiles.

In a contaminant-by-contaminant approach, we have shown that dietary acrylamide (formed in carbohydrate-containing foods during frying or baking at high temperatures, incl. fried potato products, bread, cereals and coffee) intake during pregnancy and foetal growth: an increase in acrylamide intake during pregnancy was associated with the risk of being small for gestational age at birth, and to the birth length.
Six categories of mothers were selected and associated with 8 mixtures identified from exposure of 1806 women before pregnancy in EDEN, 1666 during pregnancy in EDEN and 15226 during pregnancy in ELFE. The mothers in 5 of the 6 categories had exposures to the substances from the mixtures 3 to 4 times higher. Six of the eight mixtures were the same in the 3 databases. One was mainly composed with trace elements, furans and polycyclic aromatic hydrocarbons, and 3 mixtures with mainly pesticides. We have shown positive associations between exposure to mixtures during pregnancy and cognitive development of the children in EDEN. The main contributors to these mixtures, pesticides (fruits and vegetables) and mycotoxins (cereals products), were also positively associated to IQ. These results suggest that in this population, for specific diet, despite exposure during pregnancy to associated contaminants, the benefits of food may outweigh the potential risks associated to contaminants.

First, the project will allow to improve knowledge about the associations between environmental contaminants and child health. If the results would show a risk of some dietary contaminants on health, additional works should then be considered to confirm them and to consider Public Health decisions. Data will be created and given available for the study of other outcomes than growth and cognitive development.

A paper was published in the Environmental Research and has shown an association between acrylamide dietary intake in pregnant women and the risk for the child to be small for gestational age at birth. A paper is accepted in the journal Food and Chemical Toxicology2 on identification of mixtures of contaminants in the EDEN and Elfe cohorts and shows a robustness between both populations. This work allows to identify the mixtures to consider in toxicological and epidemiological studies.
1 Kadawathagedara Manik, et al. «Dietary acrylamide intake during pregnancy and anthropometry at birth in
the French EDEN mother-child cohort study.« Environmental research 149 (2016): 189-196.
2 Traoré Thiéma, et al. «To which mixtures are French pregnant women mainly exposed? A combination of the second French total diet study with the EDEN and ELFE cohort studies.« Food Chem Toxicol. In press
Reference: Kadawathagedara, Manik, et al. «Dietary acrylamide intake during pregnancy and anthropometry at birth in the French EDEN mother-child cohort study.« Environmental research 149 (2016): 189-196.

A link between early life factors and long-term health and chronic diseases is now well recognized. Early stages of life, i.e. the fetal and the first months of life, correspond to periods of high susceptibility. One of the main sources of exposure to chemicals during early life is food. Exposure to several contaminants present in food, like PCBs, perfluorinated compounds or recently acrylamide has been associated with growth in utero and/or during early postnatal life and impaired cognitive development. Infants are exposed to a large number of chemicals that can interact; it is thus necessary to also consider exposure to chemicals associated in mixtures as well. Furthermore, differential associations between prenatal and early postnatal exposure and postnatal outcomes have been described but rarely within the same study, preventing to study cumulative or opposite effects.
Our aim is to provide an estimation of the level of dietary contaminant exposure in French pregnant women and infants and to assess the association between the dietary exposure or mixtures of several contaminants and two developmental outcomes: growth and cognitive and motor development.
In the proposed project, prenatal and postnatal exposure will be estimated by combining information from two French birth cohorts studies (EDEN n=2,000 and Elfe n=18,300) and from the two food contamination studies (the second French Total Diet Study TDS2 and infant TDSi).
Total Diet Studies (TDS) approach has been developed in order to have an accurate estimation of diet exposure. It consists in analyzing a large range of contaminants in food, selected to represent a large portion of a typical diet, and prepared as consumed. In France, data on food contamination using this approach are available through the results of the TDS2 lead by ANSES in 2007-2008, focusing on general population, and of the infant TDS project, focusing on children under 3 years, which will be published at the end of the year (data already collected by ANSES). More than 400 chemical substances have been measured in food including inorganic contaminants, persistent organic pollutants pesticides, substances coming from food contact materials (phthalates, bisphenol A) and heat-induced contaminants.
In order to estimate dietary exposure, these data will be combined, in both EDEN and Elfe studies, to maternal food frequency questionnaires collected at birth, and covering diet in the last trimester of pregnancy and, in the EDEN study, to child 3-day dietary records collected during the first year of life. Based on these results, cocktails of exposure and associated subgroups of populations will be identified. Biomonitoring data on subsamples of women and children will be used as additional information on exposure.
Exposure to individual contaminant and mixtures will be associated with developmental health outcomes in Elfe and EDEN studies, taking into account potential confounders.
This project will provide for the first time national statistics on food chemical exposure of pregnant women based on Elfe. The study of the associations between exposure and health will allow to better understand the possible risk on growth and cognitive development, including the importance of the period of exposure, and taking into account exposure to mixtures. The results of this project will be based on a large number of data assuring a good statistical power. Moreover, this project will produce methodologies and exposure data that could be used in other projects.