350: Epigenetic changes in neonates of mothers with opioid use disorder

Chronic opioid use is associated with an increase in reactive oxygen species. These reactive oxygen species can affect DNA methylation. Little is known regarding the association of chronic opioid use disorder (OUD) in pregnancy and DNA methylation alterations related to this fetal exposure. We performed a prospective pilot study of 19 women with OUD who were enrolled in our multispecialty antepartum program (PATHways) and were prescribed buprenorphine for medication-assisted treatment. In addition, 13 controls without OUD were also enrolled. Demographic characteristics and the Perceived Stress Scale were recorded. We assessed DNA methylation patterns of key CpG sites of the FKBP5, NR3C1, and OPRM1 genes in cord blood specimens obtained from the two groups. 7 CpG sites were selected for the FKBP5 gene, 5 for the NR3C1 gene, and 13 for the OPRM1 gene. These genes were chosen because of their association with opioid metabolism and their relationship to glucocorticoid activity to interrogate differences related to stress. DNA methylation modification was also evaluated considering potential effect modifiers of buprenorphine dose and maternal age. Student t-test was used to compare groups and multiple linear regression was used for predicting the amount of methylation modified by age and buprenorphine dose. The OUD group was significantly different from the control group in that they were more likely to be tobacco users, have greater parity, and increased perceived stress. Neonates of women treated for OUD did not demonstrate a difference in the methylation of composite or individual CpG sites in the FKBP5, NR3C1, and OPRM1 genes. However, DNA methylation of the FKBP5 gene was modified by the buprenorphine dose as related to age. For older patients, as buprenorphine dose increased DNA methylation decreased, but for younger patients, as buprenorphine dose increased DNA methylation increased (p=0.03). DNA methylation of the FKBP5 gene may be altered in utero related to dose and modified by maternal age. Further testing of developmental changes in this population is needed.