Innocent Faces of Fentanyl: Opioid Use Linked to Distinct Birth Anomalies

Summary: Researchers have identified a potential new syndrome in babies born to mothers who used fentanyl during pregnancy.

The infants displayed distinctive facial features, small heads, short stature, and various physical abnormalities.

Genetic testing dismissed certain known syndromes, and the common link was maternal fentanyl use.

This raises concerns about the drug’s potential to cause life-changing birth abnormalities amidst the current fentanyl epidemic.

Key Facts:

1. Infants showed distinct symptoms such as small heads, unique facial characteristics, and multiple physical anomalies like cleft palate and “rocker bottom” feet.
2. Genetic tests ruled out known syndromes like Smith-Lemli-Opitz and fetal alcohol syndrome.
3. The mothers of all infants studied had admitted to fentanyl use during pregnancy.

Source: Nemours Children’s Health

Babies born to mothers who used fentanyl during pregnancy displayed similar facial and musculoskeletal abnormalities that suggest the emergence of a novel syndrome, according to research published in the journal Genetics in Medicine Open.

In the summer of 2022, a genetic counselor and a group of physicians at Nemours Children’s Hospital, Delaware, noticed that several infants who were referred by local neonatal intensive care units or brought to the hospital for feeding difficulties shortly after birth had similar facial features and multiple physical abnormalities, explained senior author Karen W. Gripp, MD, Chief of the Division of Medical Genetics at Nemours Children’s Health, Delaware Valley.

Gripp and colleagues enrolled six Nemours patients in a study to further assess their symptoms and characteristics. Four infants from other institutions were added later.

Gripp said the infants all had small heads, short stature, and distinctive facial features. Multiple infants had cleft palate, “rocker bottom” feet, and malformed genital organs. Other common features included short, broad thumbs, a single palmar crease, and fused toes.

Genetic testing ruled out certain suspected diagnoses, including Smith-Lemli-Opitz syndrome, a rare genetic condition. Facial feature analysis using the GestaltMatcher algorithm (FDNA Inc.) suggested that the patients did not have fetal alcohol syndrome. By ruling out these two syndromes and confirming that all the mothers had used fentanyl during pregnancy, researchers began to suspect a novel syndrome, Gripp explained.

Fentanyl is a powerful opioid which has been proven to cross the placenta and cause birth defects. Gripp said that while all the mothers of infants in this study said they had used fentanyl during pregnancy, the researchers had limited information on when they had used the drug, and in what amounts.

Gripp cautioned that further research will be necessary to determine whether fentanyl caused the abnormalities, or whether the symptoms developed due to a contaminant or another drug used at the same time.

While the initial report focuses on 10 infants, Gripp said she and colleagues have heard anecdotally about more children with similar features born to mothers who used fentanyl. Clinicians have also reported seeing patients with similar but less severe characteristics, suggesting that the novel syndrome may exist on a spectrum.

Of the 10 patients in the study, six are still receiving care through the Nemours system and are being followed for further assessment of their symptoms. Three are being followed by physicians in other states, and one patient has died. Gripp aims to identify more patients for further evaluation and care.

“Given the fentanyl use epidemic, it is important to recognize this condition,” Gripp said. “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.”

Gripp added that future research may involve efforts to definitively confirm the novel syndrome through laboratory experiments and additional studies.

About this neurodevelopment and opioid use disorder research

Author: Karen W. Gripp
Source: Nemours Children’s Health System
Contact: Karen W. Gripp – Nemours Children’s Health System
Image: Head image credited to Neuroscience News. Article image credited to Genetics in Medicine Open

Original Research: Open access.
“A novel syndrome associated with prenatal fentanyl exposure” by Karen W. Gripp. Genetics in Medicine Open

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Abstract

A novel syndrome associated with prenatal fentanyl exposure

A novel syndrome was suspected in individuals sharing short stature, microcephaly, distinctive facial features, and congenital anomalies. We enrolled 6 patients in an institutional review board approved study and evaluated medical history, findings, facial photographs, and test results across this original cohort.

Four additional cases with similar findings were contributed by clinicians from outside institutions, bringing the number of reported cases to 10 and supporting the existence of this novel syndrome.

The 6 individuals enrolled into the institutional review board approved study shared microcephaly, short stature, and distinctive facial features.

Congenital malformations included cleft palate, talipes equinovarus or rocker bottom feet, and chordee or hypospadias. Short, broad thumbs, single palmar crease, and mild 2,3 toe syndactyly were present. A hypoplastic corpus callosum was noted in 3 of 5 with appropriate evaluation. Their growth and physical findings were suggestive of Smith-Lemli-Opitz syndrome.

Biochemical studies shortly after delivery indicated abnormalities in the cholesterol metabolism pathway that subsequently resolved. No shared genomic or genetic cause was identified.

All individuals were born after a pregnancy complicated by prenatal exposure to nonprescription opioids, particularly fentanyl, suggesting fentanyl as a teratogen.

Prenatal fentanyl exposure possibly interfered with cholesterol metabolism, giving rise to findings resembling Smith-Lemli-Opitz syndrome. This novel syndrome is clinically recognizable.

Four additional cases contributed clinically shared similar findings, increasing the number of cases to 10 and supporting a novel syndrome associated with prenatal fentanyl exposure.

Assessment of Shepard and Bradford Hill criteria could be consistent with fentanyl as teratogen, though caution is necessary before assigning causality and data replication is needed.