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Multicenter Study
. 2025 Apr;45(4):458-464.
doi: 10.1038/s41372-024-02060-9. Epub 2024 Jul 20.

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

Courtney Townsel  1 , Burnley Truax  2 , Margaret Quaid  2 , Jonathan Covault  3 , Dana C Dolinoy  2 , Jaclyn M Goodrich  2
Affiliations
Multicenter Study

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

Courtney Townsel et al. J Perinatol. 2025 Apr.

Abstract

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

Methods: 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.

Results: 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.

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

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: (a) This research involving human subjects, human material, and human data was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all subjects. (b) Named ethics committee: n/a (c) Informed consent was obtained from all subjects. (d) When publishing identifiable images from human research participants, please state that the authors have obtained informed consent for publication of the images. n/a.

Figures

Fig. 1
Fig. 1
Molecular targets involved in placental regulation of fetal opioid exposure.
Fig. 2
Fig. 2. Placental DNA methylation of the ABCB1 promoter region by NOWS severity in the entire cohort and methadone-exposed pregnancies (shaded in gray).
*Significance: p value < 0.05.
See this image and copyright information in PMC

References

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