Prenatal Exposure to Everyday Chemicals Tied to Liver Injury in Kids

Prenatal environmental exposure to endocrine-disrupting chemicals was associated with a higher risk for liver injury in children, a prospective cohort study found.

In the study of over 1,000 European mother-child pairs, the likelihood of liver injury was 44-121% higher among children with prenatal exposure to organochlorine pesticides, perfluoroalkyl substances, polybrominated diphenyl ethers (PBDEs), and metals, reported Damaskini Valvi, MD, MPH, PhD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues.

They also found associations between increased levels of blood caspase-generated cytokeratin 18 (CK-18), a novel marker of hepatocyte apoptosis and non-alcoholic fatty liver disease (NAFLD) in children, with exposures to polychlorinated biphenyls and PBDEs, according to the findings in JAMA Network Open.

“We are all daily exposed to these chemicals through the food we eat, the water we drink, and the use of consumer products. This is a serious public health problem,” said Valvi in a press release. “These findings show that early life exposure to many endocrine-disrupting chemicals is a risk factor for pediatric non-alcoholic fatty liver disease.”

Diagnoses of NAFLD are increasing in the pediatric population, Valvi’s team noted, affecting anywhere from 6% to 10% of children.

“These findings can inform more efficient early-life prevention and intervention strategies to address the current non-alcoholic fatty liver disease epidemic,” coauthor Vishal Midya, PhD, also of the Icahn School of Medicine, said in a statement.

Endocrine-disrupting chemicals interfere with hormone and metabolic systems, and encompass a range of environmental pollutants used for commercial and industrial applications (plasticizers, toxic metals, pesticides, etc.), the group explained, and prior research has shown that early exposure to these chemicals can negatively affect liver development and metabolic programming, resulting in long-term hepatotoxic effects.

For their study, the researchers examined data from 2003 to 2016 from the Human Early-Life Exposome (HELIX) project — a collaborative network of six ongoing cohort studies — and included 1,108 mother-child singleton pairs from six European countries. At birth, the average age of mothers was 31. At follow-up, the average age of the children was 8.2, and 54% were boys.

Umbilical cord blood along with maternal blood or urine samples during pregnancy were evaluated for 45 endocrine-disrupting chemicals: phthalates, metals, polychlorinated biphenyls, perfluoroalkyl substances, organochlorine pesticides, phenols, parabens, organophosphate pesticides, and PBDEs.

At 6 to 11 years of age, markers of liver function were examined in the children, with injury defined as any serum level of either aspartate aminotransferase (AST), alanine aminotransferase (ALT), or γ-glutamyltransferase (GGT) above the 90th percentile.

Prenatal exposure to metals was associated with the greatest risk of liver injury (OR 2.21, 95% credible interval [CrI] 1.65-3.02), followed by perfluoroalkyl substances (OR 1.73, 95% CrI 1.45-2.09), PBDEs (OR 1.57, 95% CrI 1.34-1.84), and organochlorine pesticides (OR 1.44, 95% CrI 1.21-1.71). Prenatal exposure to metals and organochlorine pesticides were more strongly linked to an increased risk of liver injury in boys than girls.

Meanwhile, exposure to high-molecular weight phthalates (OR 0.74, 95% CrI 0.60-0.91) and phenols (OR 0.66, 95% CrI 0.54-0.78) were linked to a lower likelihood of liver injury.

Each 1-quartile increase in polychlorinated biphenyls (β=5.84 IU/L, 95% CrI 1.69-10.08) or PBDEs (β=6.46 IU/L, 95% CrI 3.09-9.92) was associated with higher CK-18 levels.

Overall, 253 of the children were classified as being at high risk for liver injury. These children were more likely to be overweight or have obesity (34% vs 17%) and belong to racial or ethnic minority groups (16% vs 4%) compared to children at low risk. Mothers of kids at high risk for liver injury were more likely to have lower educational attainment (16% vs 10%) and a higher mean body mass index (5.7 vs 4.5).

Limitations to the study included the inability to perform liver biopsies for NAFLD, and that spot urine samples may be prone to measurement errors.