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

PHILADELPHIA — The babies have small heads, underdeveloped jawbones, conjoined toes, and rounded, “rocker-bottom” feet when they are born.

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

The authors of a new study claim to have identified ten such babies, describing their constellation of symptoms as a “novel syndrome associated with prenatal fentanyl exposure.”

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

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

As a result, such children may have been misdiagnosed with Smith Lemli Opitz syndrome, a genetic condition with some of the same symptoms. She stated that this was the case with several of the Nemours children at first. Additional testing revealed that none of the children had genetic mutations that could explain the unusual symptoms, which can include genital anomalies and cleft palate.

More research is needed to prove conclusively that fentanyl causes this set of symptoms, but the evidence from these ten babies is compelling, according to Gripp.

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

Margaret J.M. Nowaczyk, a clinical geneticist at McMaster University who was not involved in the research but reviewed it at The Inquirer’s request, agreed.

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

The rise of fentanyl in Philadelphia has fueled an increasingly lethal opioid epidemic, with 1,413 people dying from overdoses by 2022. Still, it was unclear whether the syndrome had been seen at the city’s two pediatric hospitals.

St. Christopher’s Hospital for Children doctors say they haven’t seen any children with such symptoms. A spokesperson for Children’s Hospital of Philadelphia was unable to say Friday whether the hospital had such cases.

Gripp, the Nemours physician, expressed hope that the study would raise awareness so that pregnant women who use fentanyl or other opioids could receive appropriate treatment.

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

According to clinical recommendations from the American College of Obstetricians and Gynecologists, pregnant women with opioid use disorder should begin treatment with an opioid-based addiction medication, such as methadone.

This is to ensure that the fetus is not distressed during pregnancy, as well as to reduce the risk of the patient relapsing, according to the college.

An unintentional discovery

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

The patient, a 212-month-old boy with a smaller-than-average head and an underdeveloped jaw, reminded her of other recent patients with the genetic syndrome Smith Lemli Opitz.

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

However, unlike the majority of children with that condition, this boy had normal muscle tone. Furthermore, genetic tests revealed that he lacked the genetic mutations that cause SLO.

The boy’s guardian mentioned that his biological mother had used “significant” amounts of fentanyl during pregnancy, according to Gripp, who also saw the child that day.

She and Wadman went on to identify five other children with similar symptoms whose prenatal fentanyl exposure could be proven. They all had a smaller-than-average head circumference, a small jaw, a thin upper lip, and a distinct appearance that they said was difficult to describe.

The researchers did not rely solely on their own eyes. They also used AI software to analyze images of the babies’ faces, demonstrating that they had a statistically distinct set of features.

Babies born with unique medical needs

Some of the children had developmental delays as well. Others required feeding tubes. Gripp believes that attentive follow-up care will be critical.

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

Babies who were exposed to opioids or other drugs in utero are also at risk of developing neonatal abstinence syndrome (NAS). According to the CDC, they may have tremors, excessive crying, sleeping problems, and seizures.

The authors of the Nemours fentanyl study had no precise information about how much fentanyl the babies’ parents had used during pregnancy, which was one of the study’s limitations. As a result, they couldn’t tell if higher levels of drug exposure were linked to more severe symptoms, which is a common sign of a cause-and-effect relationship.

Gripp did note, however, that other research lends support to their theory that fentanyl is to blame for the infant symptoms. The drug is thought to interfere with prenatal metabolism of cholesterol, a substance essential for brain and organ development.

The mutations that cause Smith Lemli Opitz syndrome also disrupt cholesterol metabolism, which could explain why the symptoms of that genetic condition and the fentanyl-related syndrome overlap, according to Gripp.

It’s also unclear why the symptoms appear to be linked to fentanyl use but not other opioids. According to her, one possibility is that illicit fentanyl is contaminated with other substances that contribute to the syndrome.

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