Abstract
Aims:Epigenetic variation of DNA methylation of the mu-opioid receptor gene (OPRM1) has been identified in the blood and saliva of individuals with opioid use disorder (OUD) and infants with neonatal opioid withdrawal syndrome (NOWS). It is unknown whether epigenetic variation in OPRM1 exists within placental tissue in women with OUD and whether it is associated with NOWS outcomes. In this pilot study, the authors aimed to 1) examine the association between placental OPRM1 DNA methylation levels and NOWS outcomes, and 2) compare OPRM1 methylation levels in opioid-exposed versus non-exposed control placentas.Methods:Placental tissue was collected from eligible opioid (n = 64) and control (n = 29) women after delivery. Placental DNA was isolated and methylation levels at six cytosine-phosphate-guanine (CpG) sites within the OPRM1 promoter were quantified. Methylation levels were evaluated for associations with infant NOWS outcome measures: need for pharmacologic treatment, length of hospital stay (LOS), morphine treatment days, and treatment with two medications. Regression models were created and adjusted for clinical co-variates. Methylation levels between opioid and controls placentas were also compared.Results:The primary opioid exposures were methadone and buprenorphine. Forty-nine (76.6%) of the opioid-exposed infants required pharmacologic treatment, 10 (15.6%) two medications, and average LOS for all opioid-exposed infants was 16.5 (standard deviation 9.7) days. There were no significant associations between OPRM1 DNA methylation levels in the six CpG sites and any NOWS outcome measures. No significant differences were found in methylation levels between the opioid and control samples.Conclusions:No significant associations were found between OPRM1 placental DNA methylation levels and NOWS severity in this pilot cohort. In addition, no significant differences were seen in OPRM1 methylation in opioid versus control placentas. Future association studies examining methylation levels on a genome-wide level are warranted.
Highlights
Incidence of neonatal opioid withdrawal syndrome (NOWS), or neonatal abstinence syndrome (NAS), increased over four-fold from 2004 to 2014 [1]
There were no significant associations between OPRM1 DNA methylation levels in the six CpG sites and any NOWS outcome measures
No significant associations were found between OPRM1 placental DNA methylation levels and NOWS severity in this pilot cohort
Summary
Incidence of neonatal opioid withdrawal syndrome (NOWS), or neonatal abstinence syndrome (NAS), increased over four-fold from 2004 to 2014 [1]. The dose of the maternal opioid agonist medication the infant is exposed to does not predict NOWS severity, factors such as type of maternal opioid medication (methadone or buprenorphine), the infant’s gestational age (GA) and sex, breastfeeding, non-pharmacologic care, and concurrent exposures to psychiatric medications, nicotine, or illicit drugs have been associated with differences in NOWS severity [4,5,6,7]. Despite this knowledge of clinical variables, accurately predicting the disease course for each infant remains futile
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