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）：在美国，妊娠期间滥用阿片类药物和其他精神活性药物是一个严重的问题。新生儿戒断综合征（NAS）影响大多数宫内暴露于阿片类药物的婴儿，尽管其表达是可变的。NAS的最佳治疗尚未确定，目前的临床方法是将服用阿片类药物的母亲所生的所有婴儿视为有发生NAS的风险，使用标准观察方案，然后在出现NAS症状时进行治疗。这显然是次优的，因为“低风险婴儿”在医院停留太长时间，而“高风险婴儿”在开始适当的药物治疗方面有显著的延迟。由于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的关键组成部分，如果临床，人口统计学和遗传风险因素可以结合起来，以更好地识别有发展NAS风险的婴儿，这将是非常重要的。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。总体假设是，临床和遗传因素的更全面的整合将更好地识别风险婴儿 显著的NAS和指导治疗，最终将改善结果。将研究200名在怀孕期间服用阿片类药物和其他药物的母亲沿着200名接受NAS治疗的婴儿和100名暴露于阿片类药物但未发生NAS的婴儿。将收集临床、人口统计学和遗传学数据，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NAS的发病和严重程度相关。将在出生后不久分析表观遗传改变和新生儿网络神经行为量表（NNNS）评分，并在50名需要治疗NAS的婴儿和50名不需要治疗的暴露婴儿中停止治疗后再次分析。我们希望确定DNA甲基化和NNNS评分在需要治疗NAS的患者和不需要治疗的患者之间是否存在差异，以及治疗后甲基化模式和神经行为是否发生改变。这些研究的长期目标是开发一种临床预测工具，以确定NAS的风险。虽然已经知道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，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母体阿片类药物和其他药物使用对NAS中存在的变异性的影响。

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