December 17, 2020

Wayne Medicine study reveals biomarker of alcohol exposure in womb

Pediatricians and obstetricians could have another scientific weapon to yield in their pursuit of protecting newborn babies who may have been exposed to alcohol in the womb because of an original study published by researchers at the Wayne State University School of Medicine.

Until now,  animal and human studies have shown the relationship of maternal alcohol use and adverse fetal and infant effects, but studies correlating the biomarkers of alcohol exposure in the infant to adverse effects have been limited.

Professor of Pediatrics Enrique Ostrea, M.D.

“This is probably because of the absence of a biomarker of fetal exposure to alcohol, until we have shown that fatty acid ethyl esters in meconium were reliable biomarkers of fetal alcohol exposure. This finding has been corroborated thereafter by other investigators,” said Enrique Ostrea, M.D., a professor of Pediatrics and a neonatologist at Hutzel Women’s Hospital and Children’s Hospital of Michigan.

In “Fatty acid ethyl esters in meconium: A biomarker of fetal alcohol exposure and effect,” in Experimental Biology and Medicine, Dr. Ostrea and team demonstrate in a rat model a strong correlation between fatty acid ethyl esters, or FAEE, concentration in meconium to lower fetal body and brain weight, among other adverse fetal effects.

Meconium is the earliest stool of an infant, composed of materials ingested during the time the infant spends in the uterus. When people drink alcohol, it combines with certain fatty acids in the body, and FAEEs are formed.

Maternal alcoholism is a leading cause of mental retardation in children, Dr. Ostrea said.

“Since maternal alcoholism does not always result in gross physical abnormalities, such as seen in fetal alcohol syndrome and fetal alcohol syndrome disorder, quantitative FAEE in meconium may detect infants who may appear physically normal but still at risk to neurobehavioral deficits to which interventions may be helpful if initiated early enough. This further illustrates the importance of biomarkers of exposure,” he said.

At WSU, ´╗┐Dr. Ostrea developed the original meconium test and the meconium drug testing kit that is now a standard test for illicit drug exposure in newborns, and holds two United States patents for the invention. He later expanded his research on meconium analysis to study fetal exposure to environmental toxins and was awarded two multi-million dollar research grants from the National Institutes of Health and the U.S. Environmental Protection Agency.

The study launched 14 years ago at the WSU C.S. Mott Center for Human Growth and Development, by then-neonatology fellows Neil Joseph Alviedo, M.D., and Felix Banadara, M.D., as part of their research requirement. The duo, mentored by Dr. Ostrea, moved on to their pediatric residency and subspecialty boards. Dr. Ostrea and his co-authors took over the study and completed it for publication.

“Based on initial work we did that showed that meconium was an ideal matrix to measure biomarkers of prenatal exposure to xenobiotics in newborn infants, I embarked on developing the meconium test to detect fetal exposure to illicit drugs, particularly opiates (heroin), cocaine, cannabinoids, benzodiazepines, methamphetamines and more, and meconium analysis has since become a standard and more sensitive test, compared to urine analysis, to detect fetal exposure to illicit drugs,” Dr. Ostrea said. “The ability to more sensitively test illicit drug exposure with meconium analysis opened the door further to the study of adverse effects of prenatal drug exposure in infants on their growth and development.”

After the detection of illicit drugs in meconium, Dr. Ostrea expanded meconium analysis to detect exposure of legal drugs as well, particularly alcohol and nicotine, and ultimately, fetal exposure to environmental toxicants.

“The latter was an important development in meconium analysis because of concerns worldwide on the widespread use and exposure of pregnant women to environmental toxicants, especially to pesticides and heavy metals, including lead,” he said. “It has ultimately become evident through our meconium studies that the fetus is not ‘safe’ in utero as was previously thought, since it shared very well in maternal exposure to drugs and toxicants she used or was exposed to during pregnancy. I liken meconium to a ‘garbage dump’ in the fetus where all the compounds that it was exposed to during pregnancy are deposited and subject to analysis. Furthermore, since the fetus does not normally excrete its meconium until after birth, unlike urine, meconium serves as a Rosetta Stone upon which one can decipher and uncover the history of exposure of the fetus to xenobiotic agents.”

The study was supported in part by grants from the National Institute of Child Health and Human Development (R01HD039428) and the U.S. Environmental Protection Agency (RFA 2001-STAR-H1. No. R829395).

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