Association of OPRM1 and COMT Single-Nucleotide Polymorphisms With Hospital Length of Stay and Treatment of Neonatal Abstinence Syndrome

Wachman, Elisha M.; Hayes, Marie J.; Brown, Mark S.; Paul, Jonathan A.; Harvey-Wilkes, Karen; Terrin, Norma; Huggins, Gordon S.; Aranda, Jacob V.; Davis, Jonathan M.

doi:10.1001/jama.2013.3411

Cited by 174 publications

(130 citation statements)

References 21 publications

(23 reference statements)

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“…The effect of this genetic variant seems inconclusive for codeine, tramadol, and sufentanil [see online Supplemental Table 3; OPRM1, references (5-12 )]. Children who were born with the neonatal abstinence syndrome due to the in utero exposure of opioids and who carried the 118G allele had milder symptoms, illustrated by a shorter hospital stay and lower risk for any treatment of neonatal abstinence syndrome (51 ). Our study in newborn infants illustrated an increased risk for rescue analgesia with morphine while being on the ventilator in carriers of the OPRM1 118G allele in combination with the COMT 472GG genotype (52 ).…”

Section: Oprm1mentioning

confidence: 61%

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

et al. 2017

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BACKGROUND The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly. The current problem is determining which of the many potential candidates to focus on for clinical implementation. CONTENT We systematically searched publications on PGx for opioids in 5 databases, aiming to identify PGx markers with sufficient robust data and high enough occurrence for potential clinical application. The initial search yielded 4257 unique citations, eventually resulting in 852 relevant articles covering 24 genes. From these genes, we evaluated the evidence and selected the most promising 10 markers: cytochrome P450 family 2 subfamily D member 6 (CYP2D6), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), cytochrome P450 family 3 subfamily A member 5 (CYP3A5), UDP glucuronosyltransferase family 2 member B7 (UGT2B7), ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C member 3 (ABCC3), solute carrier family 22 member 1 (SLC22A1), opioid receptor kappa 1 (OPRM1), catechol-O-methyltransferase (COMT), and potassium voltage-gated channel subfamily J member 6 (KCNJ6). Treatment guidelines based on genotype are already available only for CYP2D6. SUMMARY The application of PGx in the management of pain with opioids has the potential to improve therapy. We provide a shortlist of 10 genes that are the most promising markers for clinical use in this context.

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Section: Oprm1mentioning

confidence: 61%

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

et al. 2017

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“…Recently, Wachman and colleagues have analyzed the genetic variations in OPRM1 and COMT in newborns [13], but with the focus on NAS. They have demonstrated that 118G allele carriers and 472GG (val 158 val) genotyped newborns had a shorter hospital admission and lower risk for requiring treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic polymorphisms in several genes have been associated with pain sensitivity and opioid response in both adults [10,11] and children [12]. More recently, genetic variation in newborns with the neonatal abstinence syndrome (NAS) caused by in utero opioid exposure has been related to treatment requirement and length of hospitalization [13].…”

mentioning

confidence: 99%

Rescue Morphine in Mechanically Ventilated Newborns Associated with Combined OPRM1 and COMT Genotype

et al. 2014

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“…However, these results need to be explored further for clinical application. 105 Risk factors associated with severity and intensity are summarized in Table 2. NAS may involve an initial phase that is short but intense, consisting of tremors, seizures, irritability, feeding problems, vomiting, diarrhea, hyperthermia, and other systemic signs (lasting for 1 to 2 weeks). This initial phase may be followed by a long chronic and relapsing course that includes hyperirritability, sleep disturbances, hyperphagia, and other neurologic and autonomic signs (lasting fora fewweekstoa fewmonths).…”

Section: Clinical Presentationmentioning

confidence: 99%

Neonatal Abstinence Syndrome

2014

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Neonatal abstinence syndrome (NAS) is a result of the sudden discontinuation of fetal exposure to substances that were used or abused by the mother during pregnancy. Withdrawal from licit or illicit substances is becoming more common among neonates in both developed and developing countries. NAS continues to be an important clinical entity throughout much of the world. NAS leads to a constellation of signs and symptoms involving multiple systems. The pathophysiology of NAS is not completely understood. Urine or meconium confirmation may assist the diagnosis and management of NAS. The Finnegan scoring system is commonly used to assess the severity of NAS; scoring can be helpful for initiating, monitoring, and terminating treatment in neonates. Nonpharmacological care is the initial treatment option, and pharmacological treatment is required if an improvement is not observed after nonpharmacological measures or if the infant develops severe withdrawal. Morphine is the most commonly used drug in the treatment of NAS secondary to opioids. An algorithmic approach to the management of infants with NAS is suggested. Breastfeeding is not contraindicated in NAS, unless the mother is taking street drugs, is involved in polydrug abuse, or is infected with HIV. Future studies are required to assess the long-term effects of NAS on children after prenatal exposure.

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Association of OPRM1 and COMT Single-Nucleotide Polymorphisms With Hospital Length of Stay and Treatment of Neonatal Abstinence Syndrome

Cited by 174 publications

References 21 publications

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

Rescue Morphine in Mechanically Ventilated Newborns Associated with Combined OPRM1 and COMT Genotype

Neonatal Abstinence Syndrome

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