Childhood obesity is a major public health concern: 1 in 10 children are living with obesity across Europe, which puts them at high risk of metabolic disorders and cardiovascular disease later in life. Despite its prevalence, the biological mechanisms behind obesity-related health problems remain poorly understood, and not all children with obesity develop metabolic issues.

To address this gap, researchers used an advanced “multi-layered omics” approach to examine gene expression, proteins, and metabolites in blood samples from over 800 European children, together with detailed information about their health and prenatal environment. “Prenatal life is particularly important because environmental exposures during this critical developmental period can have pronounced effects later in life,” says Martine Vrijheid, ISGlobal researcher and senior author of the study.

The study is part of the Human Early Life Exposome (HELIX) project, which follows cohorts of children from Northern Europe (Bradford, UK; and Poitiers, France) and Southern Europe (Sabadell, Spain; and Heraklion, Greece).

A high-risk cluster of children

By analysing five “omics” layers- DNA methylation, microRNAs, mRNA, proteins and metabolites- the researchers identified three distinct clusters among the children. One of these groups stood out because the children not only had higher body fat but also showed more signs of metabolic complications. This high-risk cluster showed a higher expression of inflammation markers, which indicate an overactive immune system.

“Many of these inflammatory molecules can lead to insulin resistance and trigger a chronic inflammatory loop,” explains first author Nikos Stratakis. “By focusing on clusters derived from multi-omics profiles, our approach provides a better understanding of the biological pathways involved in metabolic health, beyond traditional clinical markers,” he adds.

Early-life environmental risk factors

The researchers also looked at environmental factors during pregnancy and found that the mother’s weight before pregnancy strongly influenced whether her child fell into the high-risk group. Interestingly, the environmental exposures linked to the high-risk cluster differed depending on the region. In Northern and Western Europe, maternal exposure to the industrial chemical perfluorooctanoate (used in non-stick coatings) was a significant risk factor. In Southern / Mediterranean Europe, maternal exposure to mercury, likely from higher fish consumption, was identified as a risk factor.

“These findings help us identify modifiable risk factors that could be targeted early in life,” says Vrijheid. “They also underscore the need to tailor prevention guidelines to diverse country contexts,” she adds.