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. 2022 Apr:243:21-26.
doi: 10.1016/j.jpeds.2021.12.057. Epub 2021 Dec 28.

Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior: A Prospective Cohort Study

Marie Camerota  1 , Jonathan M Davis  2 , Lynne M Dansereau  3 , Erica L Oliveira  3 , James F Padbury  3 , Barry M Lester  4
Affiliations

Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior: A Prospective Cohort Study

Marie Camerota et al. J Pediatr. 2022 Apr.

Abstract

Objective: To determine whether pharmacologic treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior.

Study design: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted, and DNAm was examined at 4 cytosine-phosphate-guanine (CpG) sites within the OPRM1 gene. Assessment with the NICU Network Neurobehavioral Scales (NNNS) was also performed before and after NAS treatment. Changes in DNAm (DNAmpost-tx - DNAmpre-tx) and NNNS summary scores (NNNSpost-tx - NNNSpre-tx) were then calculated. Path analysis was used to examine associations among pharmacologic treatment (length of treatment [LOT] and total dose of morphine), changes in DNAm, and changes in NNNS summary scores.

Results: DNAm was significantly decreased from pretreatment to post-treatment at 1 of 4 CpG sites within the OPRM1 gene. Neonates also demonstrated decreased excitability, hypertonia, lethargy, signs of stress and abstinence, and increased quality of movement and regulation from pretreatment to post-treatment. Longer LOT and higher morphine dose were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS.

Conclusions: Pharmacologic treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior. Epigenetic changes may play a role in these changes in neonatal neurobehavior.

Keywords: DNA methylation; NAS; NICU Network Neurobehavioral Scales; OPRM1; neurobehavior; opioids.

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