A distinct pattern of birth defects has been identified in children of mothers who used fentanyl illicitly during pregnancy.
This pattern, so far reported in 10 children, appears to be a new syndrome that's never been described before, doctors reported in September in the journal Genetics in Medicine Open.
All 10 children had been exposed to multiple drugs during pregnancy, but the only substance they all had in common was fentanyl, although details of the exact timing and degree of exposure are unknown. Notably, the possibility that a contaminant in the fentanyl, rather than the opioid itself, caused the syndrome cannot yet be ruled out.
The 10 cases in the report were on the East Coast and in California, and the study authors have since become aware of four more in the Midwest, senior study author Dr. Karen Gripp, the chief of the Division of Medical Genetics at Nemours Children's Health in Wilmington, Delaware, told Live Science in an email.
"While it is still possible that the same contaminant is in street fentanyl throughout the country, the wider distribution of cases, all connected with prenatal fentanyl use disorder, may support this connection [to fentanyl alone]," she said.
When examined, the 10 infants were of short stature, had small heads and had distinctive facial features, including small lower jaws and short-length noses. Several children also had cleft palates, as well as malformed feet or genitals. Several of the infants also had short, broad thumbs or fused toes.
Some of the symptoms resembled those of Smith-Lemli-Opitz syndrome (SLOS), a developmental disorder caused by mutations in a key gene involved in making cholesterol. Genetic testing and biochemical tests ruled out this diagnosis. An analysis of the children's facial features also ruled out fetal alcohol syndrome, which is tied to specific characteristics. This analysis was corroborated by the fact that only one of the children had reportedly been exposed to alcohol in pregnancy.
The long-term prognosis for children with the syndrome is not yet known, Gripp said. One child described in the report did die at 3 months old, but the other nine survive and are being treated.
"The children we know have shown some developmental delay and feeding issues with need for a feeding tube," she said. "None are older than toddlers, so we really do not know their long term outcome."
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Six of the children were identified during treatment at Nemours Children's Health, and the remaining four were added to the study after being flagged at other institutions. Anecdotally, the team has since heard of additional children with similar symptoms whose mothers also used fentanyl during pregnancy. The severity of symptoms varies, hinting that the syndrome ranges from mild to severe.
Scientists knew fentanyl crossed the placenta and could cause birth defects — however, how it causes the specific symptoms seen in the new syndrome is not yet clear. Based on fentanyl's chemical structure, the study authors hypothesized that the opioid may derail cholesterol production by binding to key compounds involved in the process. This would help explain why the syndrome resembles SLOS.
Gripp said her team is collaborating with another lab to probe this potential cholesterol-related mechanism. They also plan to identify more patients with the syndrome. Unfortunately, "because these mothers do not receive good prenatal care, it will be difficult to document how many of their children show findings of this new syndrome," she said. Learning how prevalent the syndrome is will require an effort by large agencies, like the Centers for Disease Control and Prevention.
It's important to note that the syndrome has only been seen in children of mothers with opioid use disorder, who regularly used large amounts of fentanyl during pregnancy, Gripp said.
"That is very different from using a prescribed amount once or twice during pregnancy or delivery," she said. "In addition, the timing matters. Only drugs used early in pregnancy can result in birth defects like cleft palate. This is not caused by medication used during delivery," for example, when patients are sometimes given prescribed fentanyl for pain relief during labor.