(208) Neonatal and Maternal Adverse Outcomes Following Use of Buprenorphine and Methadone for Treatment of Opioid Use Disorder in Pregnancy

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 539

Presenting Author(s)

Elizabeth A. Suarez
– BWH Div of Pharmacoepidemiology and Pharmacoeconomics, Boston, Massachusetts, United States

Co-Author(s)

Krista Huybrechts, MS, PhD, FISPE
– Harvard Medical School, Boston, Massachusetts, United States
Loreen Straub
– Research Specialist, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, United States
Sonia Hernandez-Diaz, MD, MPH, FISPE
– Professor of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States
Hendree Jones
– UNC Horizons and Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Hilary Connery, MD, PhD
– Clinical Director, Division of Alcohol, Drugs, and Addiction, McLean Hospital, Belmont, MA, BELMONT, MA, United States
Jonathan Davis
– Department of Pediatrics, Tufts Medical Center and the Tufts Clinical and Translational Science Institute, Boston, MA, United States
Kathryn Gray
– Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, Boston, Massachusetts, United States
Barry Lester
– Center for the Study of Children at Risk, Departments of Psychiatry and Pediatrics, Alpert Medical School of Brown University, and Women and Infants Hospital, Providence, RI, United States
Mishka Terplan
– Friends Research Institute, Baltimore, MD, United States
Helen Mogun
– Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, United States
Brian Bateman
– Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA, United States

Background: Opioid agonist therapy is strongly recommended for pregnant individuals with opioid use disorder due to improved engagement with prenatal care and reducing return to opioid use and the risk of overdose. Buprenorphine may be associated with more favorable neonatal and maternal outcomes compared to methadone, but existing data are limited.

Objectives: To compare maternal and neonatal outcomes in pregnant individuals treated for opioid use disorder with buprenorphine or methadone during pregnancy.

Methods: We conducted a cohort study in publicly insured pregnant individuals in the Medicaid Analytic eXtract from 2000-2014 comparing buprenorphine and methadone. Exposure during early pregnancy (through week 19), late pregnancy (week 20 through delivery), and in the 30 days prior to delivery was assessed using dispensing and administration codes. Outcomes included neonatal abstinence syndrome, preterm birth, low birth weight, small for gestational age, cesarean delivery, and severe maternal morbidity. We estimated risk ratios (RR) and adjusted for a wide range of confounders using propensity score overlap weights, including demographics, markers for opioid use disorder history and severity, chronic conditions, concomitant medication use, and healthcare utilization.

Results: In early pregnancy, 4,349 and 1,927 pregnancies were exposed to buprenorphine and methadone, respectively. 4,331 and 2,287 were exposed to buprenorphine and methadone in late pregnancy (with 3,758 and 2,070 in the 30 days prior to delivery). After adjustment, buprenorphine compared to methadone in the 30 days prior to delivery was associated with a lower risk of neonatal abstinence syndrome (RR 0.66, 95% CI 0.62-0.70). Risk was also lower for preterm birth (RR 0.58, 95% CI 0.51-0.66), small for gestational age (RR 0.74, 95% CI 0.62-0.88), and low birth weight (RR 0.54, 95% CI 0.45-0.64) among infants exposed to buprenorphine compared to methadone in early pregnancy, and results were similar for these outcomes when exposure was defined in late pregnancy. No association was observed for cesarean delivery (RR 0.96, 95% CI 0.86-1.06) or severe maternal morbidity (RR 0.97, 95% CI 0.69-1.35). Results were consistent in sensitivity analyses that targeted unmeasured confounding and exposure misclassification.

Conclusions: Comparing opioid agonist medications in pregnancy, buprenorphine is associated with more favorable neonatal outcomes than methadone. While both medications are recommended for treating opioid use disorder during pregnancy, these results may support improving access to buprenorphine for pregnant patients.