Accelerated Fentanyl Metabolism During Pregnancy and Impact on Prenatal Drug Testing

To evaluate the metabolic pattern of illicit fentanyl in a sample of pregnant patients with opioid use disorder. Fentanyl pharmacokinetics during pregnancy are currently understudied yet the interpretation of a fentanyl immunoassay during pregnancy has significant implications on maternal legal custody and child welfare. Through this medical-legal lens, we demonstrate the utility of an emerging metric, the metabolic ratio, for accurate analysis of fentanyl pharmacokinetics during pregnancy.

We conducted a retrospective cohort analysis using the electronic medical records of 420 patients receiving integrated prenatal and opioid use disorder care at a large urban safety net hospital. Data related to maternal health and substance use were collected for each subject. The metabolic ratio was calculated for each subject to measure their rate of metabolism. The sample's (n = 112) metabolic ratios were compared with a large non-pregnant sample (n = 4366).

The metabolic ratios of our pregnant sample were significantly (p = .0001) higher than the metabolic ratios of our non-pregnant sample, indicating that the rate of conversion to the major metabolite was faster in pregnant people. The effect size for this difference between the pregnant and non-pregnant sample was large (d = 0.86).

Our findings characterize the unique metabolic pattern of fentanyl in pregnant people who use opioids, providing guidance for institutional policies around fentanyl drug testing. Additionally, our study warns of misinterpretation of toxicology results and stresses the importance of physician advocacy on behalf of pregnant women who use illicit opioids.