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A review of the genomics of neonatal abstinence syndrome.

ABSTRACT: Neonatal abstinence syndrome (NAS) is a constellation of signs of withdrawal occurring after birth following in utero exposure to licit or illicit opioids. Despite significant research and public health efforts, NAS remains challenging to diagnose, predict, and manage due to highly variable expression. Biomarker discovery in the field of NAS is crucial for stratifying risk, allocating resources, monitoring longitudinal outcomes, and identifying novel therapeutics. There is considerable interest in identifying important genetic and epigenetic markers of NAS severity and outcome that can guide medical decision making, research efforts, and public policy. A number of recent studies have suggested that genetic and epigenetic changes are associated with NAS severity, including evidence of neurodevelopmental instability. This review will provide an overview of the role of genetics and epigenetics in short and longer-term NAS outcomes. We will also describe novel research efforts using polygenic risk scores for NAS risk stratification and salivary gene expression to understand neurobehavioral modulation. Finally, emerging research focused on neuroinflammation from prenatal opioid exposure may elucidate novel mechanisms that could lead to development of future novel therapeutics.

SUBMITTER: Yen E

PROVIDER: S-EPMC9950123 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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A review of the genomics of neonatal abstinence syndrome.

Yen Elizabeth E Gaddis Nathan N Jantzie Lauren L Davis Jonathan M JM

Frontiers in genetics 20230210

Neonatal abstinence syndrome (NAS) is a constellation of signs of withdrawal occurring after birth following <i>in utero</i> exposure to licit or illicit opioids. Despite significant research and public health efforts, NAS remains challenging to diagnose, predict, and manage due to highly variable expression. Biomarker discovery in the field of NAS is crucial for stratifying risk, allocating resources, monitoring longitudinal outcomes, and identifying novel therapeutics. There is considerable in ...[more]

PMID: 36845389

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Project description:ObjectiveTo critically review and summarize current knowledge regarding the assessment of newborns with neonatal abstinence syndrome (NAS).Data sourcesWe searched the following databases for articles on the assessment of newborns with NAS that were published in English between January 2014 and June 2020: PubMed, CINAHL, and PsycINFO. Keywords and Medical Subject Heading terms used to identify relevant research articles included neonatal abstinence syndrome; Finnegan Scale; eat, sleep, console; epigenetics; genetics; pharmacokinetics; and measurement. We independently reviewed articles for inclusion.Study selectionWe retrieved 435 articles through database searches and 17 through manual reference searches; 31 articles are included in the final review. Excluded articles were duplicates, not relevant to NAS, qualitative studies, and/or of low quality.Data extractionWe used the methodology of Whittemore and Knafl to guide this integrative review. We extracted and organized data under the following headings: author, year and country, purpose, study design, participants, measurement, biomarker (if applicable), results, limitations, recommendations, and intervention.Data synthesisThe Finnegan Neonatal Abstinence Scale is the most widely used instrument to measure symptoms of NAS in newborns, although it is very subjective. Recently, there has been a transition from the Finnegan Neonatal Abstinence Scale to the eat, sleep, console method, which consists of structured assessment and intervention and has been shown to decrease length of hospital stay and total opioid treatment dose. Researchers examined biomarkers of NAS, including genetic markers and autonomic nervous system responses, on the variation in incidence and differential severity of NAS. In the included articles, women with opioid use disorder who were treated with naltrexone during pregnancy gave birth to newborns without NAS diagnoses. However, most women who were treated with buprenorphine gave birth to newborns with NAS diagnoses.ConclusionNAS negatively affects newborns in a multitude of ways, and the objective assessment and measurement of the newborn's response to withdrawal remains understudied and needs further investigation.

Project description:ImportanceIncidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.ObjectiveTo compare pharmacological therapies for neonatal abstinence syndrome.Data sourcesSystematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018).Study selectionRandomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.).Data extraction and synthesisData extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis.Main outcomes and measuresThe primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.ResultsEighteen trials (N = 1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision.Conclusions and relevanceThe current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.

Project description:BackgroundMethadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.MethodsWe conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference.ResultsTreatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events.ConclusionsThese results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).

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A review of the genomics of neonatal abstinence syndrome.

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A review of the genomics of neonatal abstinence syndrome.

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