Associations of Pregnant Maternal Brain Cho/Cr on 1H-MR Spectroscopy in the Dorsal Anterior Cingulate Cortex with Opioid Exposure

Jonathan A Class ¹ Ramana V Vishnubhotla ¹ Yi Zhao ¹ Nathan Ooms ² David Haas ¹ Senthilkumar Sadhasivam ³ Rupa Radhakrishnan ^1*

• ¹ School of Medicine, Indiana University Bloomington, Indianapolis, United States
• ² Purdue University, West Lafayette, Indiana, United States
• ³ University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States

There is growing interest in understanding the effects of opioid use on the brain; yet the effects of opioid use on the pregnant maternal brain are still relatively unknown. Pregnant women with opioid exposure during pregnancy are at high risk for adverse neurological and neuropsychiatric outcomes. Much of what is currently known about the impact of opioids on the maternal brain is mainly derived from studies in animal models, however species-specific opioid pathways and other socio environmental factors complicate the interpretation of results. A few studies in non-pregnant adults have shown utility of magnetic resonance spectroscopy (MRS) in risk prediction in substance exposure. We know that pregnancy alters the pharmacodynamic and pharmacokinetics of opioid metabolism and impact of opioids on synapses may differ from non-pregnant state. We therefore sought to understand neurometabolic alterations in pregnant women on medications for opioid use disorder (MOUD). In our multicenter study, we utilized 1H MRS to analyze metabolic alterations in the dorsal anterior cingulate cortex (dACC) in pregnant women on MOUD (12 subjects) versus pregnant control women (21 subjects) without substance exposure. Using multivariable linear regression, we identified a positive association between opioid exposure and Choline/Creatine (Cho/Cr) ratios after correcting for gestational age and scanner site. We also identified a significant elevation in Cho/Cr ratio in pregnant women on MOUD and concomitant polysubstance exposure when compared to pregnant women on MOUD without exposure to other substances and control pregnant women. These altered metabolite concentrations that we identified in the dACC may provide a mechanistic understanding of the neurobiology of MOUD and insights for better management and outcomes.