ArticleThe Journal of pediatrics2014
Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.
Article in The Journal of pediatrics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Guideline
- Neonatal Abstinence Syndrome Severity Index Predicts 18-Month Neurodevelopmental Outcome in Neonates Randomized to Morphine or Methadone.The Journal of pediatrics · 2020Trial
- Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial.Journal of perinatology : official journal of the California Perinatal Association · 2015Trial
- DNA Methylation of Neurodevelopmental, Stress-Response, Reward, and Opioid Pathway Genes: Sex Differences in Infants with Neonatal Opioid Exposure.medRxiv : the preprint server for health sciences · 2026Article
- Animal Models of Prenatal Opioid Exposure: Insights into Impaired Neurodevelopment.Advances in experimental medicine and biology · 2026Review
- Prediction of site-specific pharmacologic therapy among newborns with neonatal opioid withdrawal syndrome.Journal of perinatology : official journal of the California Perinatal Association · 2025Article
- Increased risk of severe neonatal opioid withdrawal syndrome in pregnancies with low placental ABCB1 DNA methylation.Journal of perinatology : official journal of the California Perinatal Association · 2025Article
- Early life epigenetics and childhood outcomes: a scoping review.Pediatric research · 2025Article
- Research progress of DNA methylation on the regulation of substance use disorders and the mechanisms.Frontiers in cellular neuroscience · 2025Review
- Epigenome-wide association study of placental co-methylated regions in newborns for prenatal opioid exposure.Environmental epigenetics · 2025Article
- Prenatal opioid exposure and the early life epigenome: results from ECHO.Journal of substance use · 2025Article
- Biospecimens in the HEALthy Brain and Child Development (HBCD) Study: Rationale and protocol.Developmental cognitive neuroscience · 2024Article
- Fetal and Infant Effects of Maternal Opioid Use during Pregnancy: A Literature Review including Clinical, Toxicological, Pharmacogenomic, and Epigenetic Aspects for Forensic Evaluation.Children (Basel, Switzerland) · 2024Review
- Effect of prenatal and early post-natal oxycodone exposure on the reinforcing and antinociceptive effects of oxycodone in adult C57BL/6 J mice.Psychopharmacology · 2024Article
- Article
- Synaptic Structure and Transcriptomic Profiling of Reward and Sensory Brain Areas in Male Mice of Fentanyl Addiction.Substance abuse and rehabilitation · 2024Article
- Neonatal opioid toxicity: opioid withdrawal (abstinence) syndrome with emphasis on pharmacogenomics and respiratory depression.Archives of toxicology · 2023Review
- An epigenetic synopsis of parental substance use.Epigenomics · 2023Review
- Potential problems and solutions of opioid-based treatment in neonatal opioid withdrawal syndrome (NOWS): a scoping review protocol.BMJ open · 2023Article
- A review of the genomics of neonatal abstinence syndrome.Frontiers in genetics · 2023Review
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 1 country.
Funding
Abstract
objectiveNeonatal abstinence syndrome (NAS) from in utero opioid exposure is highly variable with genetic factors appearing to play an important role. Epigenetic changes in cytosine:guanine (CpG) dinucleotide methylation can occur after drug exposure and may help to explain NAS variability. We correlated DNA methylation levels in the mu-opioid receptor (OPRM1) promoter in opioid-exposed infants with NAS outcomes. STUDY
designDNA samples from cord blood or saliva were analyzed for 86 infants who were being treated for NAS according to institutional protocol. Methylation levels at 16 OPRM1 CpG sites were determined and correlated with NAS outcome measures, including need for treatment, treatment with ≥ 2 medications, and length of hospital stay. We adjusted for covariates and multiple genetic testing.
resultsSixty-five percent of infants required treatment for NAS, and 24% required ≥ 2 medications. Hypermethylation of the OPRM1 promoter was measured at the -10 CpG in treated vs nontreated infants (adjusted difference δ = 3.2% [95% CI, 0.3-6.0%], P = .03; nonsignificant after multiple testing correction). There was hypermethylation at the -14 (δ = 4.9% [95% CI, 1.8%-8.1%], P = .003), -10 (δ = 5.0% [95% CI, 2.3-7.7%], P = .0005), and +84 (δ = 3.5% [95% CI, 0.6-6.4], P = .02) CpG sites in infants requiring ≥ 2 medications, which remained significant for -14 and -10 after multiple testing correction.
conclusionsIncreased methylation within the OPRM1 promoter is associated with worse NAS outcomes, consistent with gene silencing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.