Abstract

In humans, studies based on Developmental Origins of Health and Disease (DOHaD) concept and targeting short half-lived chemicals, including many endocrine disruptors, generally assessed exposures from spot biospecimens. Effects of early-life exposure to atmospheric pollutants were reported, based on outdoor air pollution levels. For both exposure families, exposure misclassification is expected from these designs: for non-persistent chemicals, because a spot biospecimen is unlikely to capture exposure over windows longer than a few days; for air pollutants, because indoor levels are ignored. We developed a couple-child cohort relying on deep phenotyping and extended personal exposure assessment aiming to better characterize the effects of components of the exposome, including air pollutants and non-persistent endocrine disruptors, on child health and development. Pregnant women were included in SEPAGES couple-child cohort (Grenoble area) from 2014 to 2017. Maternal and children exposure to air pollutants was repeatedly assessed by personal monitors. DNA, RNA, serum, plasma, placenta, cord blood, meconium, child and mother stools, living cells, milk, hair and repeated urine samples were collected. A total of 484 pregnant women were recruited, with excellent compliance to the repeated urine sampling protocol (median, 43 urine samples per woman during pregnancy). The main health outcomes are child respiratory health using early objective measures, growth and neurodevelopment. Compared to former studies, the accuracy of assessment of non-persistent exposures is expected to be strongly improved in this new type of birth cohort tailored for the exposome concept, with deep phenotyping and extended exposure characterization. By targeting weaknesses in exposure assessment of the current approaches of cohorts on effects of early life environmental exposures with strong temporal variations, and relying on a rich biobank to provide insight on the underlying biological pathways whereby exposures affect health, this design is expected to provide deeper understanding of the interplay between the Exposome and child development and health.

Highlights

  • From the population of SEPAGES feasibility study, we demonstrated that, when it comes to estimating the effects of exposures averaged over windows of a week or more, collecting three urine samples per day is not expected to entail bias, compared to a collection of all daily urine samples; this applies even for compounds with strong within-subject variability, such as bisphenol S [36]

  • A 13-character identifier was generated for each questionnaire, biological sample, healthFrom and exposure so that two piecesthat of information from aused given not identified previousdata, studies, it was shown some approaches inparticipant the past in are epidemiology to by the same code

  • In turn lead to biasallows in dose-response functions statistical power [33,36,37,79,80]

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Summary

Introduction

A large number of toxicological studies showed biological or adverse health effects due to developmental exposures [6,7]. These toxicological studies relate to persistent chemicals such as polychlorinated biphenyls (PCBs) [6,7] and non-persistent chemicals, which include phthalates [8], phenols such as bisphenol A [9], parabens or triclosan [10], and many other chemical families. A few toxicological experiments have reported possible effects of pregnancy exposure to particulate matter, notably in mice [11,12]; additional studies are warranted here, in particular on animal models with a placenta closer to that of humans than the mouse placenta

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