Challenges to studying the health effects of early life environmental chemical exposures on children's health

Abstract

Epidemiological studies play an important role in quantifying how early life environmental chemical exposures influence the risk of childhood diseases. These studies face at least four major challenges that can produce noise when trying to identify signals of associations between chemical exposure and childhood health. Challenges include accurately estimating chemical exposure, confounding from causes of both exposure and disease, identifying periods of heightened vulnerability to chemical exposures, and determining the effects of chemical mixtures. We provide recommendations that will aid in identifying these signals with more precision.

Fig 1. Urinary bisphenol A concentrations (ng/mL) from three hypothetical subjects over the course of approximately one week.

Dashed lines represent average BPA concentration of all urine samples for each individual and were set arbitrarily to 1, 2, and 3 ng/mL. The x-axis denotes the sequential number of the collected urine sample. The figure illustrates that a single randomly chosen sample from an individual may not represent their average exposure and could misclassify them as having lower or higher exposure than their true exposure. Moreover, a single urine sample cannot reliably distinguish differences in BPA concentrations between individuals because the within-person variation in BPA concentrations is greater than the between-person variation. BPA, bisphenol A.

Fig 2

Hypothetical relations between (A) bisphenol A exposure, packaged food consumption, and obesity risk and (B) prenatal mercury exposure, fish consumption, and brain development. In panel A, a study is investigating whether bisphenol A is associated with increased risk of obesity and packaged food intake is associated with greater bisphenol A exposure and higher obesity risk. This is an example of positive confounding, where adjusting for packaged food consumption will cause the association between bisphenol A exposure and obesity to become weaker. In Panel B, we are investigating whether mercury exposure is associated with adverse brain development and fish consumption is associated with greater mercury exposure and better brain development. This is an example of negative confounding, and adjusting for fish consumption will make the association between mercury exposure and brain development stronger.