Clinical markers of neonatal opioid withdrawal syndrome: onset, severity and longitudinal neurodevelopmental outcome

新生儿阿片戒断综合征的临床标志物：发病、严重程度和纵向神经发育结果

• 批准号: 10589940
• 负责人: Liz D Conradt
• 金额: $ 77.45万
• 依托单位: WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589940
• 关键词: Acoustics; Address; Adult; Affect; Age; Birth; Caregivers; Characteristics; Child; Childhood; Clinical; Clinical Markers; Cognitive; Collaborations; Crying; Data; Development; Diagnosis; Drug Exposure; Drug abuse; Enrollment; Environment; Epidemic; Exhibits; Exposure to; Follow-Up Studies; Functional disorder; Funding; Goals; Government; Hair; Health; Hospital Charges; Hospitalization; Hospitals; Hour; Hyperactivity; Impairment; Incidence; Infant; Infant Care; Intervention; Language Development; Length of Stay; Life Style; Longitudinal Studies; Measures; Methods; Modeling; Motor; National Institute of Drug Abuse; Neonatal Abstinence Syndrome; Neurodevelopmental Impairment; Newborn Infant; Opioid; Outcome; Participant; Pathway interactions; Pharmaceutical Preparations; Pharmacological Treatment; Pilot Projects; Policies; Pregnancy; Pregnant Women; Protocols documentation; Psyche structure; Publishing; Recording of previous events; Resources; Rhode Island; Risk; Risk Behaviors; Severities; Sex Differences; Site; Sleep; Stress; Substance Withdrawal Syndrome; Symptoms; Testing; Time; Treatment Protocols; Tremor; United States; United States National Institutes of Health; Universities; Utah; Woman; clinical predictors; cohort; design; drug withdrawal; evidence base; feeding; fetal drug exposure; fetal opioid exposure; fetal substance exposure; follow up assessment; follow-up; high risk; human subject protection; improved; in utero diagnosis; infancy; insight; interest; intergenerational; neurobehavior; neurobehavioral; neurodevelopment; novel; opioid epidemic; opioid exposure; opioid use; personalized medicine; pharmacologic; postnatal; predictive marker; pregnant; prenatal; prenatal exposure; prescription opioid; prevent; prospective; public health emergency; recruit; reduce symptoms; research clinical testing; retention rate; risk minimization; screening; social health determinants; sociodemographic predictors; sociodemographics; socioeconomics; standard of care; substance use; success; tool; transmission process

ABSTRACT Every 20 minutes in the United States, a newborn is born exposed to opioids. Approximately 50-80% of these newborns will develop Neonatal Opioid Withdrawal Syndrome (NOWS), characterized by autonomic instability, hyperactivity, irritability, tremors, abnormal cry, and difficulty feeding and sleeping. Standard of care dictates that these newborns should be placed on a 96-hour “hold” in the hospital for observation of NOWS. However, this prolonged hospital stay can lead to both pharmacological and nonpharmacological treatment and even longer hospitalization. For newborns that do develop NOWS, evidence suggests that non-pharmacological interventions could reduce the symptoms of NOWS if intervention is implemented before symptoms of NOWS are detected. The goal of this proposal is to test four novel, noninvasive clinical predictors of NOWS in newborns and as markers of neurodevelopmental impairment at 6 and 18 months: Newborn neurobehavioral assessments, newborn cry, prenatal substance exposure measured via maternal hair, and adverse socioeconomic environments. We correctly identified 86.1% of newborns diagnosed with NOWS using our NNNS and cry data in our pilot studies. If replicated, these findings could lead to personalized treatment regimens and improved care for newborns. The identification of these factors could also provide insights into the pathophysiology and clinical presentation of NOWS. We will conduct longitudinal neurodevelopmental assessments at 6 and 18 months to determine whether these markers predict developmental impairment at these ages. We will also examine whether a diagnosis of NOWS predicts neurodevelopmental impairment at 6 and 18 months. These data will provide clinicians and caregivers with valuable information about the extent to which a NOWS diagnosis portends difficulties in cognitive, motor, or language development in infancy and toddlerhood. We will enroll 312 newborns and their caregivers across two sites: Women and Infants Hospital of Rhode Island and the University of Utah Hospital. Both sites have begun collecting pilot data and have demonstrated success in recruiting 8 newborns/month. The MPIs have an almost 10-year history of collaboration and have published over 20 articles together. In both sites they have established high recruitment and retention rates. The scientific aims of this study are complimented and informed by a carefully designed recruitment and retention plan, and protection of human subjects protocol intended to minimize risk to all participants and provide appropriate resources to caregivers and newborns. When our aims are realized, we will have generated novel and objective predictors of NOWS onset and severity, as well as neurodevelopmental impairment at 6 and 18 months. This longitudinal study will establish a cohort of newborns with prenatal opioid exposure that we plan to retain for long-term neurodevelopmental follow-up into childhood. We also address one of the most pressing societal and health issues of our time, the opioid crisis, to generate data that could lead to reductions in the severity of NOWS.

抽象的 在美国每20分钟，一个新生儿就暴露于阿片类药物。其中约有50-80％ 新生儿将发展为新生儿阿片类药物戒断综合征（现在），其特征是自主不稳定， 多动症，易怒，震颤，异常哭泣以及困难的喂养和睡眠。护理标准指示 这些新生儿应在医院内的96小时“持有”以观察Nows。然而， 这个长时间的住院住院可能会导致药理和非药物治疗，甚至可以导致 住院时间更长。对于现在发展的新生儿，有证据表明非药物学 如果在现在的症状之前实施干预措施，干预措施可能会减轻现态的症状 被检测到。该提案的目的是测试现在的四个新颖的​​无创临床预测指标 新生儿和在6和18个月的神经发育障碍的标记：新生儿神经行为 评估，新生儿哭泣，通过材料头发测量的产前物质和不良 社会经济环境。我们正确地确定了86.1％的新生儿使用我们的新生儿 在我们的试点研究中，nnns和哭泣的数据。如果复制，这些发现可能会导致个性化治疗 方案和改善新生儿的护理。这些因素的识别也可以为 NOWS的病理生理学和临床表现。我们将进行纵向神经发育 在6和18个月的评估，以确定这些标记是否预测发育障碍 这些年龄。我们还将检查现在对现在的诊断现在的诊断神经发育障碍在6 和18个月。这些数据将为临床医生和照顾者提供有关范围的宝贵信息 现在的诊断预示着婴儿期的认知，运动或语言发展的困难 幼儿。我们将在两个地点注册312名新生儿及其护理人员：妇女和婴儿医院 罗德岛和犹他大学医院。这两个站点都已经开始收集试验数据，并具有 在每月招募8个新生儿方面取得了成功。 MPI有将近十年的历史 合作，并共同发表了20篇文章。在两个站点中，他们都建立了高级招聘 和保留率。这项研究的科学目的是由精心设计的 招募和保留计划，以及对人类受试者协议的保护，旨在最大程度地降低所有人的风险 参与者并为护理人员和新生儿提供适当的资源。当我们的目标实现时，我们 将产生Nows发作和严重性的新颖和客观的预测指标，以及 6个月和18个月的神经发育障碍。这项纵向研究将建立一群新生儿 我们计划将产前阿片类药物暴露保留，以进行长期神经发育的随访。 我们还解决了当时最紧迫的社会和健康问题之一，即阿片类药物危机 可能导致NOWS严重性降低的数据。