Aligning evidence and practice: comparing buprenorphine dosing and clinical outcomes across pregnant and non-pregnant populations

The National Institute on Drug Abuse awarded Vanderbilt University Medical Center $825,492 on July 15, 2026, under the Drug Use and Addiction Research Programs (CFDA 93.279) to conduct a comparative analysis of buprenorphine dosing and clinical outcomes across pregnant and non-pregnant populations with opioid use disorder.

The research addresses the gap between clinical evidence and practice in medication-assisted treatment during pregnancy. The study assesses national and state-level differences in buprenorphine dosing patterns between pregnant and non-pregnant women with opioid use disorder, examines how dosing has evolved in response to fentanyl availability, and determines relationships between dosing levels and clinical outcomes including treatment retention, neonatal outcomes, and overdose prevention. The research responds to documented underdosing in pregnancy despite pharmacokinetic evidence that up to 89 percent of pregnant women require higher buprenorphine doses during pregnancy, and to Medicaid policy restrictions that implicitly discourage dose escalation in this population.

Performance extends from July 15, 2026, through April 30, 2031, with work performed in Forest Hills, Tennessee. The award is classified as a Project Grant under the Drug Use and Addiction Research Programs, which supports basic, clinical, translational, and implementation research to develop knowledge and approaches for prevention, diagnosis, and treatment of drug use, misuse, addiction, and overdose.

Abstract

Vanderbilt university medical center drug overdose is the leading cause of pregnancy-associated death in several U.S. States, with medicaid covering over 80% of pregnant women with opioid use disorder (OUD). Among medicaid-covered births, an estimated 28.4 per 1,000 involve a birthing woman with OUD. Buprenorphine is one of the most effective and accessible medications for OUD, offering distinct advantages during pregnancy-including improved neonatal outcomes, greater accessibility compared to methadone, and a lower risk of respiratory depression and overdose. Optimizing buprenorphine dosing during pregnancy is essential-particularly in the fentanyl ERA, where higher doses are often needed to achieve and maintain treatment response. Research in non-pregnant cohorts has demonstrated clear dose-response relationships, with improved treatment retention at doses up to 32 MG/day. Similar patterns are suggested among pregnant women, who experience metabolic changes that further increase the need for dose adjustments. Pharmacokinetic data and randomized controlled trials have shown that up to 89% of pregnant women require higher buprenorphine doses during pregnancy, reinforcing the need for dose adjustment. Despite this, dosing during pregnancy remains highly variable and suboptimal, likely influenced by vague clinical guidance, therapeutic inertia, and restrictive medicaid policies. Nearly all state medicaid programs impose daily dosage caps, and many include language that implicitly discourages dose escalation in pregnancy, contributing to underdosing and preventable adverse outcomes. This study aims to: (1) assess national and state-level differences in buprenorphine dosing between pregnant and non-pregnant women with OUD, including how dosing patterns have evolved over time and in response to fentanyl; (2) determine the effectiveness of varying buprenorphine dosing thresholds on treatment continuation, stratified by pregnancy status and timing of dose adjustments; and (3) apply a discrete event simulation (DES) model to estimate the long-term clinical and economic consequences of suboptimal buprenorphine dosing. The model will project outcomes such as treatment discontinuation, overdose, postpartum treatment continuation, infant outcomes, life expectancy, healthcare utilization, and the cost-effectiveness of medicaid dosing restrictions versus evidence-based strategies. Findings from this project will generate urgently needed evidence to inform clinical guidelines and medicaid policy, identify dosing thresholds that maximize retention and minimize harm, and support the delivery of high-value, tailored treatment strategies for pregnant and non-pregnant women with OUD.