Placental DNA methylation and associations with neonatal opioid withdrawal syndrome, a pilot study.

AIMS

Epigenetic variation of DNA methylation of the mu-opioid receptor gene () 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 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 DNA methylation levels and NOWS outcomes, and 2) compare methylation levels in opioid-exposed non-exposed control placentas.

METHODS

Placental tissue was collected from eligible opioid ( = 64) and control ( = 29) women after delivery. Placental DNA was isolated and methylation levels at six cytosine-phosphate-guanine (CpG) sites within the 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 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 placental DNA methylation levels and NOWS severity in this pilot cohort. In addition, no significant differences were seen in methylation in opioid control placentas. Future association studies examining methylation levels on a genome-wide level are warranted.