Getting enough folic acid during pregnancy is linked to lower chances of fatty liver in mothers and liver damage in their children caused by prenatal exposure to harmful chemicals, according to a new study funded by NIEHS. Higher maternal blood concentrations of cobalt, a component of vitamin B12, further diminished the harmful liver effects of these exposures in children.

For most women of child-bearing age, whether pregnant or not, the U.S. Department of Health and Human Services Office on Women’s Health recommends 400 to 800 micrograms of folic acid daily from dietary supplements and fortified foods in addition to intake in other food.

“Folic acid fortification in recent years has helped many people to meet their estimated average requirements of folate, but inadequate intake rates are still concerning, especially in groups at risk, such as pregnant women,” said senior author Damaskini Valvi, M.D., Ph.D., from the Icahn School of Medicine at Mount Sinai in New York.

“While more confirmatory research is needed, these findings suggest that nutritional interventions to address folate and cobalt deficiencies during pregnancy could help mitigate the detrimental effects of environmental chemical exposures on liver health, particularly in children,” said Thaddeus Schug, Ph.D., a health scientist administrator in the Population Health Branch at NIEHS.

Measuring metabolism-disrupting chemicals

The new study published in the Journal of Hepatology involved 234 mothers and 205 children drawn from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. It examined the effects of prenatal exposures to metabolism-disrupting chemicals on maternal and childhood liver injury.

Researchers measured exposure to mixtures of 43 metabolism-disrupting chemicals in the blood or urine of pregnant women from 2007 to 2011. Mixtures included air pollutants, nonessential and essential metals, phthalates, and organophosphate pesticides. The researchers also assessed folic acid supplementation and maternal blood levels of cobalt. They followed mother-child pairs for a decade, looking for liver injury and a condition called steatosis in which fat builds up in the liver and can progress to more advanced stages of liver disease.

At approximately 9 years of age, children showed elevated levels of two liver enzymes in their blood associated with prenatal exposures to both high- and low-molecular weight phthalates and air pollutant mixtures, indicating liver injury promoted by these exposures. Adequate maternal blood cobalt concentrations attenuated the association of air pollutants and nonessential metals with liver injury in children.

Folic acid supplementation lessens chemicals’ effects

For mothers, only low-molecular weight phthalates and potentially air pollutants were associated with the presence of steatosis. For mothers and children, folic acid supplementation of 600 micrograms or greater per day during pregnancy lessened most of the effects associated with pollutants.

Previously, little was known about the impact of metabolism-disrupting chemicals on steatotic liver disease and any beneficial effects of folic acid supplementation.

“The new findings are important as they can inform the future design of clinical interventions and precision environmental health approaches to mitigate the chemicals’ effects and protect liver health in exposed women and their children,” Valvi said.