(94) Vascular Changes in the Placentas of Opioid Exposed Pregnancies

Background & Introduction: Prenatal opioid use has emerged as an issue of significant concern in the United States and has known links to neonatal opioid withdrawal syndrome (NOWS) and other adverse outcomes. Medications for opioid use disorder (MOUD) such as buprenorphine and methadone are considered vital to the treatment of OUD in pregnancy. As opioids themselves, MOUD are known to cause NOWS. Previous studies suggest that chronic opioid exposure is associated with pathologic changes to placental vasculature that can have potential health consequences for mothers and their babies both during and beyond the gravid period. Given that kappa and mu receptors are present in the placenta, endogenous opioids are believed to have regulatory effects on the temporary organ. Exogenous opioids may thus disrupt this regulation. Examining the biological effects of MOUD in pregnancy may identify ways we can prevent adverse effects while still properly treating OUD. We aimed to characterize levels of potential markers of abnormal vascular remodeling and impaired exchange in the vessels of opioid exposed pregnancies.

Methods: We conducted a pilot study including pregnant women with and without a diagnosis of OUD at Carilion Roanoke Memorial Hospital in Roanoke, VA. For this analysis, we enrolled 4 opioid-exposed and 4 opioid-unexposed pregnancies. Participants were matched on age, gestational age, and smoking status. Biopsies were collected from four distinct quadrants of each placenta after delivery and fixed, then subsequently immunostained, imaged using confocal microscopy, and analyzed for type IV collagen (COLIV), alpha-smooth muscle actin (alpha-SMA), and platelet endothelial cell adhesion molecule-1 (PECAM-1) expression via ImageJ. Mixed models were used to compare vascular metrics. Terminal villi were examined given their role in maternal-fetal transfer. Ratios of COLIV and alpha-SMA normalized to PECAM-1 (endothelial cell) percentages represented collagen and smooth muscle content by vessel, respectively. The study team was blinded to the sample groups.

Results: Study participants were non-Hispanic white with an average age of 31.4 years. Mean gestational age at delivery was 40 weeks and 0 days. All of the opioid-exposed participants were taking buprenorphine. We examined a total of 50 vessels across 27 terminal villi from the 8 placentas, 18 from opioid-exposed pregnancies and 32 from control pregnancies. We observed no significant differences in COLIV or alpha-SMA content between our opioid-exposed and control placentas.

Conclusion & Discussion: To our knowledge, this is the first study to examine the microvasculature of opioid-exposed placentas using confocal microscopy. No significant differences in collagen and smooth muscle content were seen between opioid-exposed and control placentas. It remains that various factors may account for a lack of effect. Whether an opioid is a partial or full agonist may determine the degree of change seen in the placenta. Dosing, timing of treatment during pregnancy, and medication consistency may also influence any potential changes. These results may be reassuring given that buprenorphine is a first-line addiction treatment during pregnancy.

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