A Novel Workflow to Screen for Illicit Drug Exposure in Newborns

筛查新生儿非法药物暴露的新工作流程

基本信息

批准号：
9912559
负责人：
Adam David Kennedy
金额：
$ 22.5万
依托单位：
BAEBIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2020-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9912559
关键词：
Academy Acute Address Advisory Committees Affect Alcohol or Other Drugs use American Amphetamines Behavioral Benzodiazepines Biological Assay Birth Blood specimen Clinical Cocaine Congenital Abnormality Custom Development Diagnosis Diagnostic Diarrhea Discipline of obstetrics Drug Exposure Drug Withdrawal Symptoms Early identification Enzyme Immunoassay Exposure to Family Feces Fentanyl Goals Gold Growth Guidelines Gynecology Hospitalization Hospitals Hour Illicit Drugs Incidence Intervention Laboratories Length Measures Meconium Methamphetamine Methodology Methods Microfluidics Morphine Mothers Neonatal Abstinence Syndrome Neonatal Screening Newborn Infant Ohio Opioid Outcome Patient Self-Report Pediatric Hospitals Pediatrics Performance Perinatal Pharmaceutical Preparations Pharmacological Treatment Pharmacology Phase Pregnancy Premature Birth Prenatal care Preparation Process Protocols documentation Public Health Readiness Reagent Recording of previous events Reference Standards Research Resolution Risk Running Sampling Seizures Services Sleep Sleep disturbances Social support Standardization Substance abuse problem System Technology Term Birth Testing Texas Time Toxicology Translating Tremor Urine Vomiting Withdrawal Symptom base college combat cost design digital family support feeding fetal gastrointestinal hospital laboratories improved in utero innovation instrument maternal opioid use novel novel strategies opioid use performance tests pre-clinical preclinical evaluation programs sample collection screening screening panel standard of care tool treatment planning

项目摘要

ABSTRACT A Novel Workflow to Screen for Illicit Drug Exposure in Newborns (RFA-DA-19-019) Neonatal abstinence syndrome (NAS) refers to a spectrum of withdrawal symptoms in newborns who were exposed to illicit or addictive substances in utero. Babies with NAS have higher rates of fetal anomalies (congenital malformations, growth restriction, ischemic placental complications) and perinatal issues (preterm delivery, poor feeding, sleep difficulties, diarrhea, seizures), which together raise the risk for adverse long term outcomes. Rates of NAS have skyrocketed during the last decade and estimates suggest that 5% of mothers use at least one addictive drug during their pregnancy. To address this public health crisis, multiple groups including the American College of Obstetrics and Gynecology and the American Academy of Pediatrics recommend universal screening of substance use in pregnancy using standardized behavioral scoring tools. Unfortunately, such tools are often biased due to subjective scoring or self-reporting errors, and fail to identify babies who did not receive proper prenatal care. Early identification of NAS is essential for referral of affected babies for interventions, including pharmacological treatments and behavioral/social support for the family. Select hospitals in Ohio and Texas are already engaged in universal toxicology based newborn screening (NBS) for NAS, and several state public health programs are evaluating feasibility to incorporate NAS screening into their standard NBS panels. While toxicology NBS for NAS is expanding in the U.S., several factors currently restrict the growth of such programs. These include: limited sensitivity and short history of exposure with existing tests for urine and blood samples, challenging methodologies for meconium sample processing, limited testing options for meconium samples, and long turnaround times for the few existing meconium tests. The potential consequences of delayed or otherwise insufficient NAS screening include increased errors and/or delays in pharmacologic treatments, high costs associated with unnecessary hospitalization, and increased risk for misdiagnosis. To combat these challenges, we propose a novel workflow that will enable rapid toxicology screening of urine or meconium samples in the hospital. Our system will pair a simple sample preparation protocol with a high sensitivity panel of homogeneous enzyme immunoassays recognizing five common classes of drugs: fentanyl, morphine, amphetamine/methamphetamine, cocaine, and benzodiazepines. The tests will be automated on an innovative digital microfluidic analyzer with a total time to result, including sample processing time, of under 2 hours. The product of this research meets the goals of RFA-DA-19-019 to develop “innovative methods to identify and treat newborns exposed to opioids” and will furthermore support the goals of the American Academy of Pediatrics to expand high sensitivity NAS screening. The potential benefits from implementation of our protocol include reduced length of hospitalization for unaffected newborns, accelerated time to confirmatory results, faster resolution of acute withdrawal symptoms, and improved referral to family/maternal support services.

抽象的筛查新生儿非法药物暴露的新工作流程 (RFA-DA-19-019) 新生儿戒断综合征（NAS）是指新生儿戒断症状的谱系。患有 NAS 的婴儿在子宫内接触非法或成瘾物质的胎儿畸形率较高。（先天畸形、生长受限、缺血性胎盘并发症）和围产期问题（早产）分娩、喂养不良、睡眠困难、腹泻、癫痫），这些因素共同增加了长期不良反应的风险过去十年中，NAS 的发病率急剧上升，估计有 5% 的母亲患有 NAS。为了解决这一公共卫生危机，多个团体在怀孕期间使用至少一种成瘾药物。包括美国妇产科学院和美国儿科学会建议使用标准化行为评分工具对妊娠期物质使用进行普遍筛查。不幸的是，此类工具常常由于主观评分或自我报告错误而存在偏差，并且无法识别未接受适当产前护理的婴儿。早期识别 NAS 对于转诊受影响的婴儿进行干预措施至关重要，包括药物干预俄亥俄州和德克萨斯州的部分医院已经开始为该家庭提供治疗和行为/社会支持。 NAS 的基于普遍毒理学的新生儿筛查 (NBS)，以及一些州公共卫生计划评估将 NAS 筛查纳入其标准 NBS 面板的可行性，同时进行毒理学 NBS。 NAS 正在美国扩张，目前有几个因素限制了此类计划的发展，其中包括：现有的尿液和血液样本检测灵敏度有限且接触史短，具有挑战性胎便样本处理方法、胎便样本有限的测试选项以及长期少数现有胎便测试的周转时间延迟或其他情况的潜在后果。 NAS 筛查不足包括药物治疗错误增加和/或延误、成本高与不必要的住院治疗相关，并增加误诊的风险。为了应对这些挑战，我们提出了一种新颖的工作流程，可以对尿液或尿液进行快速毒理学筛查。我们的系统将简单的样品制备方案与高通量相结合。均质酶免疫测定灵敏度小组可识别五种常见药物：芬太尼、吗啡、苯丙胺/甲基苯丙胺、可卡因和苯二氮卓类药物的测试将在一台计算机上实现自动化。创新的数字微流体分析仪，获得结果的总时间（包括样品处理时间）低于 2 这项研究的产品符合 RFA-DA-19-019 开发“识别创新方法”的目标。并治疗接触阿片类药物的新生儿”，并将进一步支持美国科学院的目标儿科扩大高灵敏度 NAS 筛查实施我们的方案的潜在好处。包括缩短未受影响新生儿的住院时间、加快获得确认结果的时间、更快解决急性戒断症状，并改善向家庭/孕产妇支持服务的转介。