Placental DNA methylation profiles in opioid-exposed pregnancies and associations with the neonatal opioid withdrawal syndrome

Genomics. 2021 May;113(3):1127-1135. doi: 10.1016/j.ygeno.2021.03.006. Epub 2021 Mar 9.

Abstract

Opioid abuse during pregnancy can result in Neonatal Opioid Withdrawal Syndrome (NOWS). We investigated genome-wide methylation analyses of 96 placental tissue samples, including 32 prenatally opioid-exposed infants with NOWS who needed therapy (+Opioids/+NOWS), 32 prenatally opioid-exposed infants with NOWS who did not require treatment (+Opioids/-NOWS), and 32 prenatally unexposed controls (-Opioids/-NOWS, control). Statistics, bioinformatics, Artificial Intelligence (AI), including Deep Learning (DL), and Ingenuity Pathway Analyses (IPA) were performed. We identified 17 dysregulated pathways thought to be important in the pathophysiology of NOWS and reported accurate AI prediction of NOWS diagnoses. The DL had an AUC (95% CI) =0.98 (0.95-1.0) with a sensitivity and specificity of 100% for distinguishing NOWS from the +Opioids/-NOWS group and AUCs (95% CI) =1.00 (1.0-1.0) with a sensitivity and specificity of 100% for distinguishing NOWS versus control and + Opioids/-NOWS group versus controls. This study provides strong evidence of methylation dysregulation of placental tissue in NOWS development.

Keywords: Biomarkers; In utero drug exposure; Neonatal abstinence syndrome; Neonatal withdrawal syndrome; Opioid; Opioid use disorder; Pregnancy.

MeSH terms

  • Analgesics, Opioid* / adverse effects
  • Artificial Intelligence
  • DNA Methylation
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Neonatal Abstinence Syndrome* / diagnosis
  • Neonatal Abstinence Syndrome* / drug therapy
  • Neonatal Abstinence Syndrome* / genetics
  • Placenta
  • Pregnancy

Substances

  • Analgesics, Opioid