New study points to cause of Fetal Fentanyl Syndrome
Adapted from an article written by John Keenan, University of Nebraska Medical Center
Researchers at Vanderbilt, in partnership with the University of Nebraska Medical Center and Nemours Children’s Hospital, have suggested an explanation, and possible pathway to prevention, for Fetal Fentanyl Syndrome. FFS causes distinctive physical birth defects, including cleft palate, distinctive facial features, and unusually small heads.
Ned Porter, research professor of chemistry and Stevenson Chair, emeritus, co-authored a paper in Molecular Psychiatry that analyzes FFS and its similarity to the metabolic disease Smith-Lemli-Opitz syndrome (SLOS). He partnered closely with Vanderbilt Research Assistant Professors Keri Tallman and Hye-Young Kim, and co-authors Karoly Mirnics, director of the UNMC Munroe-Meyer Institute; Zeljka Korade, UNMC pediatrics professor; and Karen Gripp, geneticist at Nemours Children’s Health. The Porter Research Group has studied SLOS in collaboration with UNMC researchers for over a decade.
The physical findings of FFS are similar to those seen in SLOS, but FFS is related to non-prescription fentanyl use by mothers during early and mid-pregnancy.
Due to the similarities between both diseases, the team proposed that the mechanism by which SLOS and FFS arise are related. After further research, the team suggested the cause of FFS may be fentanyl’s disruption of the baby’s ability to make cholesterol, related to fentanyl exposure in the womb.
“Fentanyl not only impairs the synthesis of cholesterol, but it also leads to the build-up of the same highly toxic sterols in cells that are found in SLOS patients,” Porter said.
Porter and his colleagues, all experts in free radical chemistry—the study of atoms, molecules, or ions that have at least one unpaired electron in the outer shell—have found that one of these toxic sterols, 7-dehydrocholesterol, is extremely vulnerable to free radical reactions with oxygen.
“It seems likely that the presence of this compound during fetal development plays a large part in these syndromes,” he said.
In the study, researchers used multiple cell models to test whether fentanyl could be interfering with the body’s ability to make cholesterol, potentially leading to FFS. They exposed different types of mouse and human cells to fentanyl, which resulted in the disruption of multiple steps in the cholesterol-making process. The results also posed another question: Why don’t all children of mothers using non-prescription fentanyl end up with FFS?
The researchers found that cells with one mutated copy of the gene that causes SLOS are increasingly susceptible to adverse effects of fentanyl.
“The effects of fentanyl may be exacerbated by some prescription medications if taken at the same time during a pregnancy,” Porter said. “It’s been a surprise to find so many highly prescribed medications that cause the same biochemical effect as does fentanyl. Fentanyl exposure while taking one or more of these prescription medications will likely compound the effect of fentanyl alone.”
The researchers stressed that fentanyl is safe when prescribed and used appropriately, and that further validation studies are needed in pregnant mouse models and human patients. These studies are ongoing and are a focus of a new grant application to the National Institutes of Health.