Predictors of the Rate of Illicit Fentanyl Metabolism in a Cohort of Pregnant Individuals.

Introduction: Illicit fentanyl use is growing in the United States, including among pregnant persons. Despite the prevalence of illicit fentanyl in the drug supply, the pharmacokinetics of fentanyl remains understudied, especially for pregnant individuals. The variability of fentanyl pharmacokinetics influences detection of fentanyl in urine samples, the results of which can have significant legal consequences. For pregnant and parenting individuals, these legal consequences may include termination of parental rights.

Methods: Through this medical-legal lens, we conducted a retrospective cohort analysis using the electronic medical records of women receiving integrated prenatal care and substance use disorder treatment. A total of 420 medical records were reviewed and 112 individuals who had a positive fentanyl immunoassay and met the selection criteria were included. Metabolic ratios (level of norfentanyl/level of fentanyl) were calculated for each study individual. A linear regression analysis was used to determine if the following physiologic factors were predictors of the rate of fentanyl metabolism: hepatic function, renal function, body mass index, medication dosage, gestational age, and maternal age.

Results: Results indicated that advanced maternal age predicted a slower conversion of fentanyl to norfentanyl, whereas increased gestational age predicted a faster conversion.

Conclusions: Variations in fentanyl metabolism in pregnancy highlight the importance of clinician vigilance when interpreting fentanyl rests results, especially for individuals with advancing maternal age. In such cases, clinician caution and advocacy may prevent unwarranted and unjust removal of a child from maternal custody.