Dataset Information

Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.

ABSTRACT: OBJECTIVE:Neonatal 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 DESIGN:DNA 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. RESULTS:Sixty-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 ? = 3.2% [95% CI, 0.3-6.0%], P = .03; nonsignificant after multiple testing correction). There was hypermethylation at the -14 (? = 4.9% [95% CI, 1.8%-8.1%], P = .003), -10 (? = 5.0% [95% CI, 2.3-7.7%], P = .0005), and +84 (? = 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. CONCLUSIONS:Increased methylation within the OPRM1 promoter is associated with worse NAS outcomes, consistent with gene silencing.

SUBMITTER: Wachman EM

PROVIDER: S-EPMC4145036 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.

Wachman Elisha M EM Hayes Marie J MJ Lester Barry M BM Terrin Norma N Brown Mark S MS Nielsen David A DA Davis Jonathan M JM

The Journal of pediatrics 20140701 3

<h4>Objective</h4>Neonatal 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.<h4>Study design</h4>DNA samples from cord blood or saliva were analyzed fo ...[more]

PMID: 24996986

Similar Datasets

Project description:The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care in maternal and fetal/neonatal (M-F/N) medicine. The standard of care for illicit or prescription opioid dependence during pregnancy is opioid agonist (methadone or buprenorphine) substitution therapy, which are also frequently abused. The next generation of pharmacotherapies for the treatment of illicit or prescription opioid addiction in the M-F/N interactional dyad must take into consideration the interplay between genetic, epigenetic, and environmental factors. Addiction to illicit drugs during pregnancy presents unique challenges to effectively treat the mother, and the developing fetus and infant after delivery. New pharmacotherapies should be safe to the developing fetus, effective in treating the physical and psychological consequences of addiction in the mother, and reduce the incidence and severity of NAS in the infant after birth. More pharmacotherapeutic options should be available to the physician such that a more individualized rather than a one-drug/strategy-fits-all approach can be used. A myriad of new and exciting pharmacotherapeutic strategies for the treatment of opioid dependence and addiction are on the horizon. This review focuses on such three strategies: (i) pharmacotherapeutic targeting of the serotonergic system; (ii) mixed opioid immunotherapeutics (vaccines); (iii) pharmacogenomics as a therapeutic strategy to insure personalized care. We review and discuss how these strategies may offer additional treatment modalities for the treatment of M-F/N during pregnancy and the treatment of the infant after birth.

Project description:ImportanceSubstantial increases in both neonatal abstinence syndrome (NAS) and maternal opioid use disorder have been observed through 2014.ObjectiveTo examine national and state variation in NAS and maternal opioid-related diagnoses (MOD) rates in 2017 and to describe national and state changes since 2010 in the US, which included expanded MOD codes (opioid use disorder plus long-term and unspecified use) implemented in International Classification of Disease, 10th Revision, Clinical Modification.Design, setting, and participantsRepeated cross-sectional analysis of the 2010 to 2017 Healthcare Cost and Utilization Project's National Inpatient Sample and State Inpatient Databases, an all-payer compendium of hospital discharge records from community nonrehabilitation hospitals in 47 states and the District of Columbia.ExposuresState and year.Main outcomes and measuresNAS rate per 1000 birth hospitalizations and MOD rate per 1000 delivery hospitalizations.ResultsIn 2017, there were 751 037 birth hospitalizations and 748 239 delivery hospitalizations in the national sample; 5375 newborns had NAS and 6065 women had MOD documented in the discharge record. Mean gestational age was 38.4 weeks and mean maternal age was 28.8 years. From 2010 to 2017, the estimated NAS rate significantly increased by 3.3 per 1000 birth hospitalizations (95% CI, 2.5-4.1), from 4.0 (95% CI, 3.3-4.7) to 7.3 (95% CI, 6.8-7.7). The estimated MOD rate significantly increased by 4.6 per 1000 delivery hospitalizations (95% CI, 3.9-5.4), from 3.5 (95% CI, 3.0-4.1) to 8.2 (95% CI, 7.7-8.7). Larger increases for MOD vs NAS rates occurred with new International Classification of Disease, 10th Revision, Clinical Modification codes in 2016. From a census of 47 state databases in 2017, NAS rates ranged from 1.3 per 1000 birth hospitalizations in Nebraska to 53.5 per 1000 birth hospitalizations in West Virginia, with Maine (31.4), Vermont (29.4), Delaware (24.2), and Kentucky (23.9) also exceeding 20 per 1000 birth hospitalizations, while MOD rates ranged from 1.7 per 1000 delivery hospitalizations in Nebraska to 47.3 per 1000 delivery hospitalizations in Vermont, with West Virginia (40.1), Maine (37.8), Delaware (24.3), and Kentucky (23.4) also exceeding 20 per 1000 delivery hospitalizations. From 2010 to 2017, NAS and MOD rates increased significantly for all states except Nebraska and Vermont, which only had MOD increases.Conclusions and relevanceIn the US from 2010 to 2017, estimated rates of NAS and MOD significantly increased nationally and for the majority of states, with notable state-level variation.

Dataset Information

Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.

Publications

Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure