Fentanyl in Labor Epidural Can Affect Results of Maternal and Neonatal Toxicology Tests
Key findings
- This prospective study measured the effect of neuraxial fentanyl administration in the labor epidural on the results of 165 peripartum maternal urine toxicology tests and 13 neonatal tests
- In the maternal cohort, using mass spectrometry, 77% of participants had a positive intrapartum result for fentanyl or its metabolite norfentanyl, and 91% had a positive postpartum test result
- Using the immunoassay method, 40% of participants had a positive intrapartum toxicology test, and 62% had a positive test postpartum
- 77%–80% of neonatal specimens were positive, depending on the test method
- Epidural anesthesia should always be considered as a possible etiology of a positive peripartum maternal or neonatal toxicology test to avoid false assumptions of nonprescribed use
Fentanyl, routinely used as part of neuraxial analgesia in labor, crosses the placenta and has been detected in neonatal urine after delivery. A positive maternal or neonatal test for fentanyl can have significant consequences for peripartum individuals, including incarceration, referrals to child protective services and loss of custody, dismissal from substance use treatment programs, stigma, and anxiety.
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Researchers at Massachusetts General Hospital conducted the first prospective study to evaluate the impact of neuraxial analgesia on the results of peripartum maternal and neonatal fentanyl toxicology testing. They found neuraxial fentanyl can lead to a positive toxicology test, a result that might be erroneously attributed to nonprescribed fentanyl use. Molly R. Siegel, MD, a clinical fellow in the Department of Obstetrics & Gynecology, Sarah N. Bernstein, MD, a maternal-fetal medicine specialist and obstetrical director for the HOPE Clinic, and colleagues published their findings in the American Journal of Obstetrics and Gynecology.
Methods
The team prospectively studied 33 pregnant adults with term singleton pregnancies who were planning a vaginal delivery with neuraxial analgesia. A history of substance use disorder was one of the criteria for exclusion.
Laboratory analyses of 165 maternal urine specimens and 13 neonatal urine specimens were performed using two commonly used methods for fentanyl testing in U.S. hospitals: immunoassay and liquid chromatography-tandem mass spectrometry.
Pre-analgesia Specimens
Three participants were unable to void before the initiation of neuraxial analgesia. The 30 others provided a single urine specimen before analgesia:
- Mass spectrometry (n=30)—All specimens were negative for fentanyl and its metabolite norfentanyl
- Immunoassay (n=29)—All specimens were negative (one had insufficient volume)
Intrapartum Specimens
30 participants provided a total of 76 intrapartum specimens after the initiation of neuraxial anesthesia:
- Mass spectrometry—Positive for 77% of participants and 65% of specimens
- Immunoassay—Positive for 40% of participants and 39% of 75 specimens (one had insufficient volume)
The fentanyl measurements obtained with mass spectrometry increased with increasing duration of neuraxial analgesia (P<0.001).
Postpartum Specimens
21 participants provided a total of 59 specimens after delivery and before hospital discharge:
- Mass spectrometry—Positive for 91% of participants and 78% of specimens
- Immunoassay—Positive for 62% of participants and 54% of 57 specimens (two had insufficient volume)
Fentanyl in maternal urine decreased with increasing time after cessation of neuraxial analgesia (P=0.03). Still, most specimens remained positive on mass spectrometry analysis for >24 hours after delivery (maximum, 42 hours and 50 minutes). The longest period for a positive result on immunoassay was 39 hours and 54 minutes.
Neonatal Specimens
Of the 13 neonatal specimens:
- 77% were positive on mass spectrometry
- 5 could be analyzed by immunoassay; of those, 80% were positive for fentanyl
Specimens analyzed by mass spectrometry were collected until 29 hours and 50 minutes after birth, and that was also the longest time a specimen remained positive. Specimens analyzed by immunoassay were collected until 20 hours and 5 minutes after birth, and that was also the longest duration of positivity.
Guidance for Clinicians
Considering the potential consequences of a positive peripartum maternal or neonatal toxicology test, epidural anesthesia should always be considered a possible etiology to avoid false assumptions of nonprescribed use.
These results should not be interpreted as suggesting that neuraxial analgesia is unsafe or should be withheld because of the potential for a positive fentanyl test. There is robust evidence available about the efficacy of epidural anesthesia and its long-term safety for women and neonates.
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