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Fentanyl exposure during pregnancy is linked to a new medical syndrome in babies

Illicit fentanyl use has been on the rise for years. Now, a new study suggests a link between the drug and certain birth defects.  (Pixabay)
By Tom Avril and Aubrey Whelan Philadelphia Inquirer

PHILADELPHIA – The babies are born with small heads, underdeveloped jawbones, conjoined toes and rounded, “rocker-bottom” feet.

Physicians at Nemours Children’s Health say they all have one thing in common: They were exposed in utero to significant amounts of fentanyl, a dangerous synthetic opioid.

In a new study, the authors say they’ve identified 10 such babies so far, describing their constellation of symptoms as a “novel syndrome associated with prenatal fentanyl exposure.”

Six of the children were identified at Nemours clinics in Delaware. Four others were identified by physicians in California, Boston and Rhode Island who are coauthors of the study, published this fall in Genetics in Medicine Open.

While illicit fentanyl use has been on the rise for years, no one had previously established a link between the drug and these birth defects. That’s likely because children born to parents who use the drug may not receive regular medical care, or their pediatricians may not know the parents’ medical history, said senior study author Karen W. Gripp, chief of the Nemours division of medical genetics.

As a result, such children may have been misdiagnosed as having a genetic condition with some of the same symptoms, called Smith Lemli Opitz syndrome. She said that’s what happened at first with several of the Nemours children. After additional testing, none turned out to have genetic mutations that could explain the unusual symptoms, which also can include genital anomalies and cleft palate.

Further study is needed to prove definitively that fentanyl causes this collection of symptoms, but the evidence from these 10 babies is compelling, Gripp said.

“We have enough information to feel confident to say yes, there is something here,” she said.

McMaster University clinical geneticist Margaret J.M. Nowaczyk, who was not involved with the research but reviewed it , agreed.

“We’re going to see more of these children, that’s my gut feeling,” she said.

In Philadelphia, the rise of fentanyl has fueled an increasingly deadly opioid epidemic, with 1,413 people dying of overdoses in 2022. Still, it was not immediately apparent if the city’s two pediatric hospitals had seen cases of the syndrome.

Physicians at St. Christopher’s Hospital for Children say they have not identified any children with such symptoms. At Children’s Hospital of Philadelphia, a spokesperson was not immediately able to say whether that hospital had such cases.

Gripp, the Nemours physician, said she hoped the study would increase awareness, so that pregnant people who use fentanyl or other opioids can get proper treatment.

Pregnant people who take opioids, whether prescribed by a doctor or not, are generally advised not to quit cold turkey during pregnancy, because entering withdrawal can cause early labor or even a miscarriage, according to the Centers for Disease Control and Prevention.

Pregnant people with opioid use disorder should instead start treatment with an opioid-based addiction medication, like methadone, according to clinical recommendations from the American College of Obstetricians and Gynecologists.

That’s to ensure that the fetus doesn’t experience distress during pregnancy – and also to reduce the risk of the patient relapsing, the college says.

A chance observationThe Nemours study was prompted by a chance observation by genetic counselor Erin Wadman at one of the health system’s clinics in August.

The patient, a 2½-month-old boy with a smaller-than-average head and an underdeveloped jaw, reminded her of other recent patients who had been diagnosed with Smith Lemli Opitz, the genetic syndrome.

“It was that kind of ‘aha’ moment, like you’re recognizing someone you think you’ve seen before in a different setting,” she said.

But unlike most children with that condition, this boy had normal muscle tone. What’s more, genetic tests revealed he did not have genetic mutations that cause SLO.

Gripp, who also saw the child that day, then obtained a key clue: The boy’s guardian mentioned that his biological mother had used “significant” amounts of fentanyl during pregnancy.

She and Wadman went on to identify five other children with similar symptoms whose prenatal exposure to fentanyl could be substantiated. All had a smaller-than-average head circumference, a small jaw, a thin upper lip and an overall distinctive appearance that they said was hard to put into words.

The researchers did not simply trust their own eyes. They also used artificial intelligence software to analyze images of the babies’ faces, demonstrating that they had a statistically distinct set of features.

Babies born with unique medical needsSome of the children also experienced developmental delays. Others have needed feeding tubes. Attentive follow-up care will be essential, Gripp said.

“That’s one of our big concerns,” she said. “How will these children fare long term?”

Babies who were exposed to opioids or other drugs in utero also are at risk of developing a kind of withdrawal known as neonatal abstinence syndrome (NAS). They may experience tremors, cry excessively and have problems with sleeping and seizures, according to the CDC.

One limitation of the Nemours fentanyl study was that the authors did not have precise information about how much fentanyl the babies’ parents had used during pregnancy. That meant they could not tell if higher levels of drug exposure were connected to more severe symptoms – a typical hallmark of a cause-and-effect relationship.

Still, Gripp noted that other research provides additional support for their theory that fentanyl is behind the infant symptoms. The drug is thought to interfere with prenatal metabolism of cholesterol, a substance that is key to the development of the brain and other organs.

The mutations that cause Smith Lemli Opitz syndrome also disrupt cholesterol metabolism, perhaps explaining the overlapping symptoms between that genetic condition and the fentanyl-related syndrome, Gripp said.

Also unclear is why the symptoms seem to be associated with the use of fentanyl but not other opioids. One possibility is that illicit fentanyl is contaminated with other substances that are contributing to the syndrome, she said.