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（由申请人提供）：妊娠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，新生儿戒断综合症（NAS）影响着大多数在子宫内接触阿片类药物的婴儿，尽管 NAS 的最佳治疗方法各不相同。尚未确定，目前的临床方法是将所有服用阿片类药物的母亲所生的婴儿视为有发生 NAS 风险的婴儿，使用标准观察方案，然后在出现 NAS 症状时进行治疗，这显然不是最理想的。因为“低风险婴儿”在医院停留的时间过长，而“高风险婴儿”在开始适当的药物治疗方面明显延迟，因为我们的研究小组已经表明，母亲和婴儿的遗传因素正在成为 NAS 的重要组成部分，如果能够结合临床、人口统计学和遗传风险因素来更好地识别有 NAS 风险的婴儿，那么确定治疗后表观遗传模式和新生儿神经行为是否发生变化也很重要。临床与遗传学的整合因素将更好地识别处于危险中的婴儿 将对 200 名在怀孕期间服用阿片类药物和其他药物的母亲以及 200 名接受 NAS 治疗的婴儿和 100 名接触阿片类药物但未发生 NAS 的婴儿进行研究。 ，并将收集遗传数据并开发 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表观遗传改变和新生儿网络相关。我们将在 50 名需要 NAS 治疗的婴儿以及 50 名不需要治疗的暴露婴儿出生后不久和停止治疗后再次分析神经行为量表 (NNNS) 评分，我们希望确定 DNA 甲基化和 NNNS 评分是否不同。这些研究的长期目标是开发一种临床预测工具来确定 NAS 的风险。 NAS。虽然已知预测工具的一些候选变量与 NAS 相关，但其他变量仍被怀疑并需要确认，而其他变量仍有待发现。通过识别这些临床和遗传风险因素，我们应该能够更好地了解 NAS。母亲阿片类药物和其他药物的使用对 NAS 存在变异性的影响。

项目成果

The Genomics of Neonatal Abstinence Syndrome.

新生儿戒断综合症的基因组学。

• 发表时间: 2017
• 作者: Cole, F Sessions;Wegner, Daniel J;Davis, Jonathan M
• 通讯作者: Davis, Jonathan M

Association of a Simplified Finnegan Neonatal Abstinence Scoring Tool With the Need for Pharmacologic Treatment for Neonatal Abstinence Syndrome.

简化芬尼根新生儿戒断评分工具与新生儿戒断综合征药物治疗需求的关联。

• 发表时间: 2020
• 影响因子: 13.8
• 作者: Devlin, Lori A;Breeze, Janis L;Terrin, Norma;Gomez Pomar, Enrique;Bada, Henrietta;Finnegan, Loretta P;O'Grady, Kevin E;Jones, Hendrée E;Lester, Barry;Davis, Jonathan M
• 通讯作者: Davis, Jonathan M

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：尤尼斯·肯尼迪·施赖弗国家儿童健康和人类发展研究所、美国妇产科学院联合研讨会的执行摘要

• 发表时间: 2017
• 影响因子: 7.2
• 作者: Reddy, Uma M;Davis, Jonathan M;Ren, Zhaoxia;Greene, Michael F;Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes Workshop Invited Speakers
• 通讯作者: Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes Workshop Invited Speakers