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.

摘要 在美国，每20分钟就有一个新生儿出生时接触阿片类药物。其中约50%-80% 新生儿会患上新生儿阿片类药物戒断综合症(NOWS)，其特征是自主神经不稳定， 多动、易怒、震颤、不正常的哭声、进食和睡眠困难。护理标准规定 这些新生儿应该在医院里被“等待”96小时，以观察NOWS。然而， 这种长时间的住院可能会导致药物治疗和非药物治疗，甚至 住院时间延长。对于确实患上NOWS的新生儿，证据表明非药理学的 如果在NOWS症状出现之前实施干预，干预可以减少NOWS的症状 都被检测到。这项提案的目标是测试四种新的、无创的NOWS临床预测指标 新生儿与6个月和18个月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 社会经济环境。我们正确地识别了86.1%被诊断为NOWS的新生儿 NNNS和CRY数据在我们的初步研究中。如果重复，这些发现可能导致个性化治疗 养生和改善对新生儿的护理。对这些因素的识别也可以提供对 NOWS的病理生理和临床表现。我们将进行纵向神经发育 在6个月和18个月时进行评估，以确定这些标志物是否可以预测 这些年龄段。我们还将检查NOWS的诊断是否预示着6岁时神经发育障碍 还有18个月。这些数据将为临床医生和护理人员提供有关以下方面的宝贵信息 NOWS的诊断预示着婴儿期的认知、运动或语言发育困难，以及 蹒跚学步。我们将在两个地点招收312名新生儿和他们的照顾者：妇幼医院 罗德岛和犹他大学医院。这两个网站都已开始收集试点数据，并已 在每月招募8名新生儿方面取得成功。MPI已经有近10年的历史了 合作，并共同发表了20多篇文章。在这两个地点，他们都建立了高招聘 和保留率。这项研究的科学目标是由精心设计的 招募和保留计划以及保护人类受试者议定书，旨在将对所有人的风险降至最低 并为照顾者和新生儿提供适当的资源。当我们的目标实现时，我们 将产生新的和客观的NOWS发病和严重性预测指标，以及 6个月和18个月时出现神经发育障碍。这项纵向研究将建立一个新生儿队列 产前阿片类药物暴露，我们计划保留下来，用于儿童时期的长期神经发育跟踪。 我们还应对我们这个时代最紧迫的社会和健康问题之一--阿片类药物危机 可能导致NOWS严重程度降低的数据。