(102) Circulating EV-miRNA profile in pregnant persons with opioid use disorder treated with buprenorphine

Maternal OUD has increased with a related rise in NOWS. Buprenorphine has become one of the mainstays for MOUD. The effects of OUD and MOUD on maternal and fetal physiology are not well understood. Because circulating extracellular vesicle miRNAs (EV-miRNAs) from pregnant patients have both a maternal and fetal (placental) origin, they may serve as biomarkers of maternal and fetal health. Hence, we examined the impact of buprenorphine on circulating EV-miRNA cargo in pregnant patients.

Study Design: EV-miRNAs were isolated from the plasma of pregnant women during the 3^rd trimester (12 buprenorphine-treated and 12 healthy controls) and small RNA-sequencing was performed to identify miRNAs in both groups. For miRNAs differential presence analysis, read counts were log-10 normalized and 2-way ANOVA comparisons between groups performed with Benjaminini and Hochberg method used to control the false discovery rate (FDR). Targeted biological pathways and disease-associations were assessed with DIANA-miRpath and RNADisease, respectively.

Results: Maternal age and BMI were similar in both groups. There was no difference in timing of maternal blood for EV-miRNAs evaluation (30.7+2.7 v 31.4+2.9; p=0.56) for controls and buprenorphine respectively. A total of 508 EV-miRNAs were detected, of which 16 were differentially abundant between buprenorphine and control groups (Figure 1). Among the EV-miRNAs enriched in the buprenorphine group, hsa-miR-520f-5p, hsa-miR-520g-3p, and hsa-miR-518d-3p, belong to the placenta-specific, chromosome 19 miRNA cluster (C19MC). RNA-disease prediction analysis revealed hsa-miR-520g-3p, hsa-miR-124-3p, has-miR-1260b to be associated with preeclampsia. Moreover, many differentially present EV-miRNAs were linked to cardiovascular disease, stroke, and myocardial infarction. Targeted biological pathways linked to the EV-miRNAs included pathways in cancer, cellular senescence, regulation of actin cytoskeleton, and neurotrophin signaling.

Conclusion:

This is a novel study which identified unique alterations in circulating EV-miRNAs in buprenorphine treated patients with OUD.