Prenatal Fentanyl Exposure Association With Characteristic Neonatal Anomalies

To investigate if previously described anomalies associated with fentanyl could be identified in our cohort of individuals with active fentanyl use in pregnancy.

Potential cases of a novel syndrome were identified from a prospectively collected database of obstetric patients with substance use disorder enrolled in a multispecialty treatment program from 2014 to 2024 in this case series study. Suspected Fetal Fentanyl Syndrome (FFS) was defined as small head circumference (<10%ile) and at least one other sign: cleft palate, clubfoot, rocker bottom feet, toe syndactyly, single palmar crease, hypoplastic corpus callosum, and hypospadias. The database was screened for findings consistent with this syndrome resembling Smith-Lemli-Opitz Syndrome.

From 2014 to 2024, 639 patients were enrolled in the cohort. Of the 103 patients found to have neonates with a small head circumference, 51 individuals self-reported fentanyl use within the last year. Six of these individuals had confirmatory toxicology testing for fentanyl upon program enrollment. Of these individuals' neonates, 4 displayed characteristic anomalies consistent with FFS. All cases shared lagging head growth, while additional anomalies identified included cleft palate (n=3), short nasal tip (n=1), thin upper lip (n=1), micrognathia (n=1), and hypospadias (n=1). Genetic screening/diagnostic testing varied but an assessment of cholesterol metabolism was not performed.

In this cohort, 7.8% of individuals with self-reported fentanyl use had neonates with signs of the previously described FFS. FFS is a proposed syndrome and results should be interpreted with caution. Similar data is needed to confirm and delineate this association and determine long-term developmental effects.