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

Uppala Radhakrishna, Sangeetha Vishweswaraiah, Lavanya V. Uppala, Marta Szymanska, Jacqueline Macknis, Sandeep Kumar, Fozia Saleem-Rasheed, Buket Aydas, Ariadna Forray, Srinivas B. Muvvala, Nitish K. Mishra, Chittibabu Guda, David J. Carey, Raghu P. Metpally, Richard C. Crist, Wade H. Berrettini, Ray O. Bahado-Singh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1127-1135
Number of pages9
JournalGenomics
Volume113
Issue number3
DOIs
StatePublished - May 2021

Keywords

  • Biomarkers
  • In utero drug exposure
  • Neonatal abstinence syndrome
  • Neonatal withdrawal syndrome
  • Opioid
  • Opioid use disorder
  • Pregnancy

ASJC Scopus subject areas

  • Genetics

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