ADHD symptoms linked to early childhood exposure to polyfluoroalkyl substances

By Dr. Liji Thomas, MDReviewed by Lily Ramsey, LLMMar 28 2023

A study published in Science of the Total Environment Journal explores the association of polyfluoroalkyl substances (PFAS) exposure with attention deficit-hyperactivity disorder (ADHD) symptoms.

Study: Association between early-childhood exposure to perfluoroalkyl substances and ADHD symptoms: A prospective cohort study. Image Credit: Elms Art/Shutterstock.com

Background

With the increasing introduction of convenience-based utensils, machines, and foods, humans are exposed to many chemicals from the embryonic stage onward. The effects of most of these molecules on neurodevelopment and tumorigenesis remain unclear.

Introduction

PFAS includes a range of chemicals in the larger category of persistent organic pollutants. They are characterized by a fluorinated carbon chain, which characterizes their repellent nature to dirt, water, and oil.

The most well-known chemical from this group is probably Teflon, used worldwide for nonstick cookware, carpets, food packaging, and firefighting foams.

Unfortunately, these chemicals slowly degrade and accumulate as they move up through the food pyramid. Their half-life in the human body is 2-5 years. These facts have led to their use being phased out in several countries, including the most commonly used ones, Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Their use is being replaced by newer members like perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxs).

These are even more durable than their predecessors. Scientists are worried about the effects of these long-lived and ubiquitous molecules on the environment and, thus, on human health.

ADHD is thought by some scientists to be due to environmental effects on neurodevelopment during certain key phases of early life. This occurs via epigenetic modification and causes the individual to experience permanent disease susceptibility changes later.

During the first three years of life, children are prone to epigenetic changes mediated by endocrine-disrupting chemicals (EDC). Indeed, ADHD is reported to affect over one in fifteen children worldwide, beginning early in life. Epigenetic change may be partially mediated by the effects of heavy metals, phthalates, and possibly PFAS, but the latter is still a research area.

The study

Interestingly, some studies hint at a possible low-exposure relationship with toxicity compared to higher doses. This motivated the current study investigating non-linear dose-response (non-monotonic dose-response or NMDR) relationships between ADHD and PFAS.

In this study, early childhood exposures to six selected PFAS were studied. These were perfluorooctanoate (PFOA), perfluornonanoicacid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonate (PFOS).

The researchers measured serum levels of these substances in over 500 children at two and four years of age. They assessed the presence of ADHD traits in the same cohort at eight years of age using the ADHD Rating Scale IV (ARS). The data came from an earlier study called the Environment and Development of Children (EDC).

What did the study show?

The study included almost equal numbers of boys and girls. Six PFAS' were found to be present in over 90% of the children at both two and four years, but the mean concentrations dropped at the later time point. Only two were found more frequently at four years compared to two years, namely, PFPeA and PFTrDA.

However, all the PFAS were correlated at both time points. After adjusting for potential confounding factors, the scientists discovered that all six PFAS measured in the study showed inverted U-shaped associations with ARS scores. Compared to those in the first quartile, the highest ARS scores were seen in children falling into the second or third quartiles of exposure to PFAS. The effect was typically stronger for girls, but this varied with the PFAS measured.

The greatest changes in ARS scores were seen with PFAS measurements in the second quartile compared to the first and with PFNA and PFOS values in the third quartile compared to the first. With a doubling of PFOA and PFHxS levels at two years of age, the ARS scores increased by approximately 8% and 7%, respectively.

When PFAS mixtures were compared with ARS scores, there was an increase in scores by almost half in the second and third quartiles and by a fifth in the fourth quartile compared to the first.

When the level of exposure to all six PFAS was used as a summative value, it was observed that the ARS scores increased by a fifth commensurate with a doubling of the summed values. The peak correlation seems to be at the third quartile.

However, no associations were observed at four years of age, indicating that the neurologic effects of PFAS exposures occurring in early childhood, up to two years, impact school-age children, increasing their ADHD risk. This association is maximal with low to medium exposures.

What are the implications of the study?

This is the first study to look at PFAS exposure at two years using a wide range of PFAS.

It states: "School-aged children may be vulnerable to the neurotoxic effects of exposure to PFAS at age two that contribute to ADHD, particularly at low to mid-levels."

The scientists found significant associations between PFAS exposure at two years of age and ADHD symptoms at the age of eight years. Six PFAS showed low-dose exposure relationships with ADHD, the ARS scores being increasingly correlated with second or third-quartile exposures compared to the first.

Indicating the importance of the age of exposure, as children were found to be more vulnerable to the neurotoxic effects of PFAS exposure at two years but not four years. The study outcomes corroborate with earlier studies and are biologically plausible since the formation of neural connections and pathways for efficient brain function occurs in embryonic and fetal life, continuing into the teen years.

N-methyl-D-aspartate receptor (NMDR) relationships between PFAS exposure and liver immunologic and metabolic function have already been reported. These associations might signal the cytotoxic effects of PFAS or cell-specific receptors for these molecules, among other putative mechanisms. In response to such research, several countries have already begun regulating PFAS use.

A uniform pattern of association was not observed for all the detected PFAS, indicating the lack of data on the biological effects and toxicities of these molecules.

Further research is necessary to validate and extend these findings and tease out such associations' clinical and pathophysiological aspects.