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

• 批准号: 10162803
• 负责人: Rainer Ng
• 金额: $ 71.6万
• 依托单位: BAEBIES, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10162803
• 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

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 一个新的工作流程，用于筛选新生儿非法药物的暴露 （RFA-DA-19-019） 新生儿禁欲综合征（NAS）是指新生儿中的一系列戒断符号 在子宫内暴露于非法或其他物质。 NAS的婴儿的胎儿异常率较高 （先天性畸形，生长限制，缺血性胎盘并发症）和围产期问题（早产） 交货，喂养不良，睡眠困难，腹泻，癫痫发作），这加剧了长期不良的风险 结果。 NAS的发生率在过去十年中飙升，估计表明5％的母亲 怀孕期间至少使用一种额外的药物。为了解决这一公共卫生危机，多个小组 包括美国妇产科和美国儿科学院 建议使用标准化行为评分工具对妊娠中的物质使用进行普遍筛查。 不幸的是，由于主观评分或自我报告错误，这种工具通常会偏向偏差，并且无法识别 没有获得适当产前护理的婴儿。 NAS的早期鉴定对于转诊受影响的婴儿进行干预措施至关重要，包括药物 对家庭的治疗和行为/社会支持。俄亥俄州和德克萨斯州的精选医院已经参与 在基于通用毒理学的新生儿筛查（NB）中，NAS和几个州公共卫生计划是 评估将NAS筛选纳入其标准NBS面板的可行性。而毒理学NBS NAS在美国正在扩展，目前有几个因素限制了此类计划的增长。其中包括： 有限的敏感性和对尿液和血液样本的现有测试的暴露历史较短，挑战 胎粪样品处理的方法，胎粪样品的测试选项有限，并且很长 少数现有的胎粪测试的周转时间。延迟或其他的潜在后果 NAS筛查不足包括增加错误和/或药物治疗的延迟，高成本 与不必要的住院关系以及诊断误差的风险增加有关。 为了应对这些挑战，我们提出了一个新颖的工作流程，将使尿液的快速毒理学筛查或 胎粪样品在医院。我们的系统将将简单的样本准备协议与高 均质酶免疫测定的敏感性面板识别五类药物类别：芬太尼， 吗啡，苯丙胺/甲基苯丙胺，可卡因和苯二氮卓类药物。测试将在 创新的数字微流体分析仪，总时间为2个以下的样本处理时间，包括样本处理时间 小时。这项研究的产物符合RFA-DA-19-019的目标，以开发“创新方法来识别 并治疗接触阿片类药物的新生儿”，并将支持美国学院的目标 儿科扩大高灵敏度NAS筛查。实施我们的协议带来的潜在好处 包括减少未受影响新生儿的住院时间，加速时间以确认结果，更快 解决急性戒断症状的解决方案，并改善了转介到家庭/孕产妇支持服务。