Naloxone and Metabolites Quantification in Cord Blood of Prenatally Exposed Newborns and Correlations with Maternal Concentrations

Abstract

Objective To quantify naloxone and metabolite concentrations in newborns prenatally exposed to sublingual buprenorphine/naloxone and to correlate neonatal and maternal metabolite concentrations.

Methods This is a prospective observational cohort study. Eleven pregnant women treated for opioid use disorder with sublingual buprenorphine/naloxone were enrolled. Maternal and newborn blood was collected and analyzed for naloxone, buprenorphine, and metabolites via liquid chromatography tandem mass spectrometry. Descriptive statistics and correlation coefficients were utilized to analyze data.

Results Maternal daily naloxone and buprenorphine doses were 1 to 5 mg and 4 to 20 mg, respectively; the mean (standard deviation) time from medication until delivery was 9.9 (4.3) hours. Naloxone was below the limits of quantification (LOQ) in five infants and six mothers with a range of less than LOQ to 0.3 μg/L. There was a strong positive correlation between maternal and newborn naloxone concentrations: Spearman's ρ = 0.89 (p < 0.01). There were strong positive correlations between maternal and neonatal assays for the buprenorphine analyte concentrations: buprenorphine ρ = 0.88 (p < 0.01), norbuprenorphine ρ = 0.71 (p = 0.01), and norbuprenorphine-glucuronide ρ = 0.98 (p < 0.01), but not for buprenorphine-glucuronide, ρ = 0.53 (p = 0.10).

Conclusion Naloxone and buprenorphine are transferred to the fetus during prenatal exposure to maternal sublingual buprenorphine/naloxone. The quantity of naloxone transferred from maternal circulation is minimal and highly correlated with maternal concentrations.

Keywords

buprenorphine - naloxone - opioid use disorder - pregnancy

Note

Supported by a grant (Dr. Wiegand) from the Cefalo-Bowes Young Researcher Award Fund, Center for Maternal and Infant Health, The University of North Carolina, Chapel Hill, North Carolina; Building Interdisciplinary Research Careers in Women's Health K12 HD001441–16 (Dr. Vora).

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Health and Human Services Administration.

The authors report no conflicts of interest.

Presented at Society of Maternal-Fetal Medicine 36th Annual Meeting, February 1–6, 2016, Atlanta, Georgia.

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