The increasing incidence of a potentially cancer-causing liver disease in children has been linked to prenatal exposure to various endocrine-disrupting chemicals, Mount Sinai researchers report:†
It is the first comprehensive study on the association between prenatal exposure and mixtures of these chemicals and non-alcoholic fatty liver disease. The researchers used cytokeratin-18 as a new marker for the disease in children. The findings, reported in JAMA network opens in Julyunderline the importance of understanding prenatal exposure to environmental chemicals as a risk factor for non-alcoholic fatty liver disease, a rapidly growing childhood problem that can lead to severe chronic liver disease and liver cancer in adulthood.
“These findings may contribute to more efficient early-life prevention and intervention strategies to address the current epidemic of nonalcoholic fatty liver disease,” said Vishal Midya, PhD, lead author and postdoctoral researcher in the Department of Environmental Medicine and Public Health and a member of from the Mount Sinai Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai.
Damaskini Valvi, MD, PhD, MPH, senior author, assistant professor of environmental medicine and public health, and member of the Mount Sinai Institute for Exposomic Research at Icahn Mount Sinai, added, “We are all exposed to these chemicals on a daily basis through the foods we eat. we eat, the water we drink and the use of consumer products. This is a serious public health problem. These findings show that exposure at an early age to many endocrine-disrupting chemicals is a risk factor for non-alcoholic fatty liver disease in children, establishing the focus on additional research needed to elucidate how exposure to environmental chemicals may interact with genetic and lifestyle factors in the pathogenesis of liver disease.”
Non-alcoholic fatty liver disease is one of the most common liver diseases worldwide and is increasingly diagnosed in childhood. It affects 6 to 10 percent of the general pediatric population and about 34 percent of obese children. Hormone-disrupting chemicals are a broad class of environmental pollutants, including various pesticides, plastics, flame retardants, and toxic metals. Examples include perfluoroalkylated substances (PFAS), also known as “forever chemicals” used in non-stick cookware and food packaging, and polybrominated diphenyl ethers (PBDEs) used as flame retardants in furniture and baby products. Hormone-disrupting chemicals interfere with hormone and metabolic systems in humans. Several experimental studies have shown that exposure to these chemicals can lead to liver damage and non-alcoholic fatty liver disease; to date, however, the possible effects of prenatal exposure of mixtures to these chemicals have not been studied in humans.
In this study, researchers measured 45 chemicals in the blood or urine of 1,108 pregnant women from 2003 to 2010. The chemicals included endocrine-disrupting chemicals such as PFAS, organochlorine and organophosphate pesticides, plasticizers (phenols, phthalates), PBDEs, and parabens. When the children reached the ages of 6 to 11, scientists measured the levels of enzymes and cytokeratin-18 that indicate the risk of liver disease in the children’s blood, and found elevated levels of those biomarkers in children who were more highly exposed to environmental chemicals during pregnancy.
“By understanding the environmental factors that accelerate fatty liver, we can reduce people’s risk by giving them actionable information to make informed choices that reduce the risk or impact of the disease,” said Robert Wright, MD, MPH, Ethel H Wise Chair of the Department of Environmental Medicine and Public Health and co-director of the Institute for Exposomic Research at Icahn Mount Sinai. “Exposomics is the wave of the future because once you sequence the human genome, which is done, you can’t do much in genomics alone. The missing piece of the puzzle for us to understand different diseases is to measure their environmental causes, and Exposomics is a way to accelerate our understanding of how the environment affects our health.”
The study participants participated in the Human Early-Life Exposome project, a collaborative network of six ongoing population-based prospective birth cohort studies from six European countries: France, Greece, Lithuania, Norway, Spain and Great Britain. Limitations of this study include the inability to perform a liver biopsy, considered the gold standard to establish a causal relationship to non-alcoholic fatty liver disease, due to the risk and ethical limitations due to the children’s age. .
This research was funded by the National Institute of Environmental Health Science (NIEHS) and the European Community’s Seventh Framework Programme.
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