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

被引:21
作者
Radhakrishna, Uppala [1 ]
Vishweswaraiah, Sangeetha [1 ]
Uppala, Lavanya, V [2 ]
Szymanska, Marta [1 ]
Macknis, Jacqueline [3 ]
Kumar, Sandeep [3 ]
Saleem-Rasheed, Fozia [4 ]
Aydas, Buket [5 ]
Forray, Ariadna [6 ]
Muvvala, Srinivas B. [6 ]
Mishra, Nitish K. [7 ]
Guda, Chittibabu [7 ]
Carey, David J. [8 ]
Metpally, Raghu P. [8 ]
Crist, Richard C. [9 ]
Berrettini, Wade H. [9 ,10 ]
Bahado-Singh, Ray O. [1 ]
机构
[1] Oakland Univ, William Beaumont Sch Med, Dept Obstet & Gynecol, 3811 West 13 Mile Rd, Royal Oak, MI 48073 USA
[2] Univ Nebraska, Coll Informat Sci & Technol, Peter Kiewit Inst, Omaha, NE 68182 USA
[3] Beaumont Hlth Syst, Dept Pathol, Royal Oak, MI USA
[4] Oakland Univ, William Beaumont Sch Med, Dept Newborn Med, Royal Oak, MI 48073 USA
[5] Meridian Hlth Plans, Dept Healthcare Analyt, Detroit, MI USA
[6] Yale Sch Med, Dept Psychiat, New Haven, CT USA
[7] Univ Nebraska Med Ctr, Coll Med, Dept Genet Cell Biol & Anat, Omaha, NE USA
[8] Geisinger, Dept Mol & Funct Genom, Danville, PA USA
[9] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA
[10] Geisinger Med Clin, Danville, PA USA
关键词
Opioid; Opioid use disorder; In utero drug exposure; Pregnancy; Neonatal withdrawal syndrome; Neonatal abstinence syndrome; Biomarkers; ABSTINENCE SYNDROME; GENE-EXPRESSION; INTEGRATIVE ANALYSIS; NEWBORN-INFANTS; RECEPTOR GENE; SUBSTANCE USE; RISK-FACTORS; MORPHINE; METHADONE; DEPENDENCE;
D O I
10.1016/j.ygeno.2021.03.006
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:1127 / 1135
页数:9
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