Increased risk of severe neonatal opioid withdrawal syndrome in pregnancies with low placental ABCB1 DNA methylation

Neonatal opioid withdrawal syndrome (NOWS) is unpredictable. We assessed relationships between placental DNA methylation with in-utero opioid exposure and NOWS severity.

Secondary analysis of a prospective multicenter cohort study of pregnancies on methadone or buprenorphine, ≥34 weeks, singleton, 18 or greater. Placental biopsies were collected. Placental DNA methylation levels of ABCG1, ABCG2, CYP19A1, and HSD11B2 were quantified via pyrosequencing following bisulfite conversion. CYP19A1 mRNA levels and umbilical cord drug levels were determined by RT-qPCR and LC-MS respectively. Severe NOWS was diagnosed through Finnegan scoring. P value < 0.05 was significant.

Thirty-eight dyads were included. Promoter region methylation for placental ABCB1 was lower in severe NOWS compared to non-severe NOWS (p = 0.04). Placental CYP19A1 methylation was inversely related to CYP19A1 mRNA levels and associated with umbilical cord norbuprenorphine levels (p < 0.01), but not umbilical cord methadone levels.

Lower placental ABCB1 methylation was associated with severe NOWS. Higher placental CYP19A1 methylation correlated with higher umbilical cord norbuprenorphine levels.