Abstract / Summary
Background: /Objectives: Opioid use disorder (OUD) in pregnancy can impact pregnancy and neonatal outcomes. Placental DNA methylation has been associated with prenatal exposures and neonatal behavior. This study aimed to (1) compare placental DNA methylation in stress response genes between opioid-exposed and non-opioid exposed pregnancies, and (2) examine associations with neonatal opioid withdrawal syndrome (NOWS) in the opioid-exposed cohort.
Methods: Pregnant individuals with and without OUD were enrolled from a single center. Fresh placental villous tissue was analyzed using a custom DNA methylation panel targeting 175 CpG sites across 11 stress response genes. Mean DNA methylation levels were compared between opioid-exposed and non-exposed groups and within the opioid cohort for associations with NOWS pharmacologic treatment. Linear regression models were constructed for differentially methylated CpG sites.
Results: Of 87 participants (48 non-exposed, 39 opioid-exposed), opioid-exposed placentas showed hypermethylation at HSD11B2 and HTR1A CpG sites and hypomethylation at NR3C1 and OXT CpG sites in adjusted models. Infants with NOWS requiring pharmacologic treatment exhibited increased methylation at eight CpG sites mapping to four stress-related genes (HSD11B2, HTR1A, HTR1B, and OXTR); however, associations did not survive multiple testing correction.
Conclusions: After correction for multiple testing, we did not identify significant DNA methylation changes in stress-related genes due to prenatal opioid exposure. Larger studies are needed to understand the influence of prenatal opioid exposure on placental epigenetic modification.