An alarming suspected new syndrome has been described for the first time in newborn babies whose mothers used non-prescription opioids, "particularly fentanyl", while pregnant. Displaying a range of facial, musculoskeletal, and genital abnormalities, the infants are now being monitored to determine how their condition influences their cognitive development and overall well-being.
The pattern of birth defects was first noticed by doctors at Nemours Children’s Hospital in Delaware, where six neonates with similar abnormalities were brought for treatment in the summer of 2022. A further four babies with matching features were later identified at other facilities, bringing the total number of patients to ten.
All of the infants displayed microcephaly (small heads) as well as short stature and “distinctive facial features”. Among the congenital malformations were cleft palates, rocker bottom feet (where the soles of the feet curl upwards), short, broad thumbs, a single palm crease, and fused toes.
Some of the babies also had genital anomalies, while 60 percent of infants that had an MRI had an unusually thin corpus callosum, which is the part of the brain that links the left and right hemispheres.
Initially, doctors suspected that the ten newborns may have had a rare genetic condition called Smith-Lemli-Opitz syndrome (SLOS), which is caused by deficient cholesterol metabolism in the womb and results in a range of physical differences. However, genetic tests revealed that none of the infants carried this disorder.
Further investigation revealed that the mothers of all ten babies had used the opioid drug fentanyl while pregnant. This led researchers to suspect that the infants may have a previously unknown disorder caused by prenatal exposure to the drug.
Examinations on aborted fetuses that had been exposed to fentanyl in the womb have confirmed that the opioid does cross the placenta, while other studies have detected the drug in the fetal brain. Together, these findings suggest that fentanyl is rapidly transferred to a fetus early in pregnancy and remains in the fetal tissue for some time.
Exactly how this triggers birth defects is unclear – although given the similarities with SLOS, the authors of a new study suggest that fentanyl may disrupt cholesterol metabolism in fetuses. Other psychotropic drugs have been shown to interfere with cholesterol synthesis in the developing fetus by inhibiting a key enzyme called DHCR7, and the researchers therefore suspect that fentanyl may do the same.
“Although fentanyl’s effect on cholesterol metabolism has not been directly tested, based on indirect evidence it is biologically plausible that it affects cholesterol metabolism in the developing fetus,” write the study authors. However, due to a lack of information about exactly when in pregnancy fentanyl exposure occurred and in what amounts, it’s currently impossible to confirm whether this new syndrome is caused by the drug.
According to the researchers, the birth defects could potentially have been caused by exposure to a different substance or by contaminants or impurities in the fentanyl that the mothers used while pregnant. Nonetheless, study author Karen Gripp insisted in a statement that “given the fentanyl use epidemic, it is important to recognize this condition.”
“Analogous to prenatal alcohol exposure causing fetal alcohol syndrome with long-term physical and developmental consequences, this novel condition may impact many infants in life-changing ways,” she said.
The study is published in the journal Genetics in Medicine Open.