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 分钟就有一名新生儿接触阿片类药物。 新生儿会出现新生儿阿片戒断综合症（NOWS），其特征是自主神经不稳定， 多动、烦躁、颤抖、异常哭泣以及喂养和睡眠困难需要护理标准。 这些新生儿应在医院“留院”96 小时以进行NOWS 观察。 这种延长的住院时间可能会导致药物和非药物治疗，甚至 对于确实患有NOWS 的新生儿，有证据表明非药物治疗可能需要更长的住院时间。 如果在出现NOWS 症状之前实施干预，干预措施可以减轻NOWS 症状 该提案的目标是测试四种新型、非侵入性的NOWS 临床预测因子。 新生儿以及 6 个月和 18 个月时神经发育障碍的标志物：新生儿神经行为 评估、新生儿哭声、通过母亲头发测量的产前物质暴露以及不良反应 我们使用我们的方法正确识别了 86.1% 被诊断患有 NOWS 的新生儿。 如果复制我们的试点研究中的 NNNS 和哭泣数据，这些发现可能会导致个性化治疗。 这些因素的识别也可以提供有关新生儿的见解。 我们将进行纵向神经发育研究。 在 6 个月和 18 个月时进行评估，以确定这些标志物是否预测发育障碍 我们还将检查 NOWS 的诊断是否预示着 6 岁时的神经发育障碍。 这些数据将为教区居民和护理人员提供有关程度的宝贵信息。 NOWS 诊断预示着婴儿期认知、运动或语言发展存在困难 我们将在两个地点招募 312 名新生儿及其护理人员： 妇婴医院 罗德岛州和犹他大学医院这两个地点都已开始收集试点数据。 MPI 每月成功招募 8 名新生儿，已有近 10 年的历史。 合作并共同发表了 20 多篇文章，在这两个网站上都建立了很高的招聘规模。 这项研究的科学目标得到了精心设计的补充和启发。 招募和保留计划以及人类受试者保护协议，旨在最大限度地减少所有人的风险 当我们的目标实现时，我们会向参与者提供适当的资源。 将生成NOWS 发作和严重程度的新颖且客观的预测因子，以及 这项纵向研究将建立一组新生儿 6 个月和 18 个月时的神经发育障碍。 我们计划保留产前阿片类药物暴露，用于儿童期的长期神经发育随访。 我们还解决当今时代最紧迫的社会和健康问题之一——阿片类药物危机，以产生 可能会导致NOWS 严重程度降低的数据。