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

doi:10.1016/j.ygeno.2021.03.006

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 journal › Article › peer-review

24 Scopus citations

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 language	English (US)
Pages (from-to)	1127-1135
Number of pages	9
Journal	Genomics
Volume	113
Issue number	3
DOIs	https://doi.org/10.1016/j.ygeno.2021.03.006
State	Published - 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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10.1016/j.ygeno.2021.03.006

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Radhakrishna, U., Vishweswaraiah, S., Uppala, L. V., Szymanska, M., Macknis, J., Kumar, S., Saleem-Rasheed, F., Aydas, B., Forray, A., Muvvala, S. B., Mishra, N. K., Guda, C., Carey, D. J., Metpally, R. P., Crist, R. C., Berrettini, W. H., & Bahado-Singh, R. O. (2021). Placental DNA methylation profiles in opioid-exposed pregnancies and associations with the neonatal opioid withdrawal syndrome. Genomics, 113(3), 1127-1135. https://doi.org/10.1016/j.ygeno.2021.03.006

Radhakrishna, U, Vishweswaraiah, S, Uppala, LV, Szymanska, M, Macknis, J, Kumar, S, Saleem-Rasheed, F, Aydas, B, Forray, A, Muvvala, SB, Mishra, NK, Guda, C, Carey, DJ, Metpally, RP, Crist, RC, Berrettini, WH & Bahado-Singh, RO 2021, 'Placental DNA methylation profiles in opioid-exposed pregnancies and associations with the neonatal opioid withdrawal syndrome', Genomics, vol. 113, no. 3, pp. 1127-1135. https://doi.org/10.1016/j.ygeno.2021.03.006

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

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",

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doi = "10.1016/j.ygeno.2021.03.006",

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AU - Radhakrishna, Uppala

AU - Vishweswaraiah, Sangeetha

AU - Uppala, Lavanya V.

AU - Szymanska, Marta

AU - Macknis, Jacqueline

AU - Kumar, Sandeep

AU - Saleem-Rasheed, Fozia

AU - Aydas, Buket

AU - Forray, Ariadna

AU - Muvvala, Srinivas B.

AU - Mishra, Nitish K.

AU - Guda, Chittibabu

AU - Carey, David J.

AU - Metpally, Raghu P.

AU - Crist, Richard C.

AU - Berrettini, Wade H.

AU - Bahado-Singh, Ray O.

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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.

KW - Biomarkers

KW - In utero drug exposure

KW - Neonatal abstinence syndrome

KW - Neonatal withdrawal syndrome

KW - Opioid

KW - Opioid use disorder

KW - Pregnancy

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JO - Genomics

JF - Genomics

IS - 3

ER -

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

Abstract

Keywords

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