Establishing Risk in Neonatal Abstinence Syndrome

确定新生儿戒断综合症的风险

• 批准号: 9318501
• 负责人: Jonathan M. Davis
• 金额: $ 27.29万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9318501
• 关键词: Affect; Aftercare; Birth; Candidate Disease Gene; Clinical; DNA Methylation; Data; Development; Epigenetic Process; Genes; Genetic; Genetic study; Genomics; Genotype; Goals; Health Care Costs; Hospitalization; Hospitals; Incidence; Infant; Intervention; Lead; Length of Stay; Medical Genetics; Mental disorders; Methadone; Modeling; Modification; Morphine; Mothers; National Research Council; Neonatal; Neonatal Abstinence Syndrome; Opiates; Opioid; Outcome; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Predictive Factor; Pregnancy; Protocols documentation; Psychotropic Drugs; Public Health; Publishing; Randomized Clinical Trials; Reporting; Risk; Risk Assessment; Risk Factors; Severities; Single Nucleotide Polymorphism; Symptoms; Testing; Time; Woman; addiction; bead chip; clinical risk; common treatment; cost; disease classification; genetic risk factor; genetic variant; high risk infant; improved; improved outcome; in utero; methylation pattern; model design; neurobehavior; neurobehavioral; offspring; opioid misuse; opioid use in pregnancy; parent grant; precision medicine; public health relevance; tool; treatment strategy

 DESCRIPTION (provided by applicant): Misuse of opioids and other psychoactive drugs during pregnancy is a significant problem in the US. Neonatal abstinence syndrome (NAS) affects most infants exposed to opioids in utero, although its expression is variable. Optimal treatment of NAS has not been established and the current clinical approach is to treat all infants born to mothers taking opioids as being at risk of developing NAS, using standard observation protocols followed by treatment when symptoms of NAS appear. This is clearly sub-optimal because "low risk infants" remain in the hospital too long while "high risk infants" have significant delays in the initiation of appropriate drug therapy. Since our group has shown that genetic factors in the mother and infant are emerging as crucial components of NAS, it would be highly significant if clinical, demographic and genetic risk factors could be combined to better identify infants at risk of developing NAS. It would also be important to determine if epigenetic patterns and neonatal neurobehavior change after treatment. The overarching hypothesis is that more comprehensive integration of clinical and genetic factors will better identify infants at risk of significant NAS and guide treatment that will ultimately improve outcome. Two hundred mothers taking opioids and other drugs during pregnancy will be studied along with 200 infants treated for NAS and 100 infants who are exposed to opioids, but do not develop NAS. Clinical, demographic, and genetic data will be collected and risk assessment models of NAS will be developed. In addition, we wish to determine if epigenetic and neurobehavioral factors correlate with the onset and severity of NAS. Epigenetic alterations and Neonatal Network Neurobehavioral Scale (NNNS) scores will be analyzed shortly after birth and again after therapy has been discontinued in 50 infants who require treatment for NAS as well as 50 exposed infants who do not require treatment. We wish to determine if DNA methylation and NNNS scores differ between those who need treatment for NAS and those who do not and if methylation patterns and neurobehavior are altered after treatment. The long term goal of these studies is the development of a clinical prediction tool to establish risk of NAS. While some candidate variables for the prediction tool are already known to be associated with NAS, others are suspected and require confirmation, and others remain to be discovered. By identifying these clinical and genetic risk factors, we should be able to better understand the impact of maternal opioid and other medication use on the variability that exists in NAS.

 描述（由适用提供）：在怀孕期间滥用阿片类药物和其他精神活性药物是美国的一个重大问题。新生儿禁欲综合征（NAS）会影响大多数暴露于子宫内阿片类药物的婴儿，尽管其表达是可变的。尚未建立对NAS的最佳治疗方法，当前的临床方法是使用标准观察方案，将服用阿片类药物的母亲出生的婴儿患有患有NAS的风险，然后在出现NAS症状时进行治疗。这显然是最佳的，因为“低风险婴儿”在医院中的时间太长，而“高风险婴儿”在适当的药物治疗方面有重大延迟。由于我们的小组表明，母亲和婴儿的遗传因素正在成为NAS的关键组成部分，因此如果可以将临床，人口统计和遗传危险因素组合在一起以更好地识别有发展NAS风险的婴儿，那将非常重要。确定治疗后的表观遗传模式和新生儿神经行为是否改变也很重要。总体假设是，临床和遗传因素的更全面整合将更好地识别有风险的婴儿 大量的NAS和指导治疗将最终改善结果。在怀孕期间服用阿片类药物和其他药物的200名母亲将与200名接受NAS和100名接触阿片类药物的婴儿治疗的婴儿一起研究，但不会出现NAS。将收集临床，人口统计学和遗传数据，并将开发NAS的风险评估模型。此外，我们希望确定表观遗传和神经行为因素是否与NAS的发作和严重程度相关。表观遗传改变和新生儿网络神经行为量表（NNNS）分数将在出生后不久进行分析，并且在50名需要治疗NAS以及50名不需要治疗的暴露婴儿的婴儿中，治疗后再次分析。我们希望确定DNA甲基化和NNN的得分是否在需要NAS治疗的人和不进行治疗的人之间以及治疗后是否改变了甲基化模式和神经脱头。这些研究的长期目标是开发建立NAS风险的临床预测工具。尽管已经知道某些预测工具的候选变量与NAS相关联，但其他候选变量被怀疑并需要确认，而另一些则需要发现。通过确定这些临床和遗传危险因素，我们应该能够更好地了解母体阿片类药物和其他药物使用对NAS中存在的可变性的影响。

项目成果

Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes: Executive Summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologist

阿片类药物在妊娠、新生儿戒断综合症和儿童结局中的使用：美国妇产科学院尤尼斯·肯尼迪·施赖弗国家儿童健康和人类发展研究所联合研讨会的执行摘要

• DOI: 10.1097/aog.0000000000002426
• 发表时间: 2018
• 期刊: Obstetrics and gynecology
• 影响因子: 7.2
• 作者: Smid,Marcela;Gordon,AdamJ;Plumb,Sam;Plumb,Jennifer
• 通讯作者: Plumb,Jennifer