(310) Buprenorphine and Methadone Metabolites in Maternal and Neonatal Milieu: Relationship to Neonatal Opioid Withdrawal Syndrome

Thursday, January 30, 2025

10:30 AM – 12:30 PM

Coauthor(s)

Justine Keller, MD

MFM Fellow
Saint Louis University School of Medicine
St. Louis, Missouri, United States
JO

Jonathan Oliva, BA

Research Scientist
Saint Louis University School of Medicine
St. Louis, Missouri, United States
MM

Mohammad Abdul Motalleb, PhD

Analytical Chemist
Saint Louis University School of Medicine
St. Louis, Missouri, United States
NS

Nancy Shelley, RN

Saint Louis University School of Medicine
St. Louis, Missouri, United States

Submitting Author and Presenting Author(s)

Nikita R. Peramsetty, BS (she/her/hers)

Medical Student
Saint Louis University School of Medicine
St. Louis, Missouri, United States

Coauthor(s)

ZZ

Zidong Zhang, MPH, MS, PhD

Saint Louis University School of Medicine
St. Louis, Missouri, United States
FS

Fran Sverdrup, PhD

Associate Professor, Department of Biochemistry and Molecular Biology
Saint Louis University School of Medicine
St. Louis, Missouri, United States
Niraj R. Chavan, MD, MPH, MS (he/him/his)

Associate Professor, Program Director - Maternal Fetal Medicine Fellowship
Saint Louis University School of Medicine
St. Louis, Missouri, United States

Objective: To evaluate the relationship between maternal dose of medications for opioid use disorder (MOUD) and levels of their metabolites in maternal and neonatal cord blood as well as the association between metabolite levels and neonatal opioid withdrawal syndrome (NOWS).

Study Design: We undertook a prospective observational study of pregnant patients with opioid use disorder (OUD) seeking prenatal care at a tertiary academic medical center between 7/2022 - 6/2024. Maternal blood was collected during the antepartum period and at the delivery admission in addition to neonatal cord blood. Plasma specimen was extracted and analyzed via LCMS/MS techniques to measure levels of the parent compound (buprenorphine/methadone) and their metabolites [norbuprenorphine, buprenorphine glucuronide, norbuprenorphine glucuronide and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)] in each biological pool. Multivariable regression analyses were undertaken to evaluate the relationship between maternal MOUD dose and neonatal cord levels as well as the occurrence of NOWS requiring pharmacologic treatment.

Results: Of the 66 patients recruited, paired maternal-infant dyad specimens were available from 35 patients, including 17 on methadone and 18 on buprenorphine. Overall, 8/35 (22.8%) neonates developed NOWS requiring pharmacologic treatment, including 2/17 (11.7%) in the buprenorphine vs 6/18 (33%) in the methadone group (p=.23). Regression analyses revealed that every 1mg increase in the maternal MOUD dose was associated with a 0.118 ng/ml increase (p < .05) in buprenorphine metabolite level (n=15) and 1.3128 ng/ml increase (p < .05) of methadone metabolite level (n=18) in neonatal cord blood. We found no significant differences in maternal or cord plasma metabolite levels among neonates with and without NOWS for any of the metabolites considered.

Conclusion: Our findings reinforce the lack of a relationship between maternal MOUD dose and occurrence of NOWS even at the metabolite level, thereby allaying concerns for impact of MOUD dose on NOWS and providing reassurance for continuation of MOUD in pregnancy.