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.

摘要 一种新的工作流程来筛选新生儿中的非法药物暴露 （RFA-DA-19-019） 新生儿戒断综合征（NAS）是指新生儿出现的一系列戒断症状， 在子宫内接触非法或成瘾物质。患有NAS的婴儿有更高的胎儿畸形率 （先天性畸形、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，癫痫发作），这些共同增加了长期不良反应的风险。 结果。在过去的十年中，NAS的发病率飙升，估计有5%的母亲 在怀孕期间使用至少一种成瘾药物。为了应对这场公共卫生危机， 包括美国妇产科学院和美国儿科学会 建议使用标准化的行为评分工具对怀孕期间的物质使用进行普遍筛查。 不幸的是，这类工具往往由于主观评分或自我报告错误而存在偏见，无法识别 没有得到适当产前护理的婴儿。 早期识别NAS对于将受影响的婴儿转诊进行干预至关重要，包括药物治疗。 为家庭提供治疗和行为/社会支持。俄亥俄州和得克萨斯州的一些医院已经参与其中 在基于普遍毒理学的新生儿筛查（NBS）中，NAS和几个州的公共卫生计划 评估将NAS筛查纳入其标准NBS面板的可行性。虽然毒理学NBS为 NAS正在美国扩张，目前有几个因素限制了这些方案的发展。其中包括： 有限的灵敏度和短的暴露史与现有的测试尿液和血液样本，挑战 胎粪样本处理的方法，胎粪样本有限的检测选择， 现有的少数胎粪测试的周转时间。延迟或其他的潜在后果 不充分的NAS筛查包括增加的错误和/或药物治疗的延迟、高成本 与不必要的住院治疗有关，并增加了误诊的风险。 为了应对这些挑战，我们提出了一种新的工作流程，可以对尿液或尿液样本进行快速毒理学筛查。 医院里的胎粪样本我们的系统将一个简单的样品制备协议与一个高的 均相酶免疫测定灵敏度组识别五种常见药物：芬太尼， 吗啡、安非他明/甲基安非他明、可卡因和苯二氮卓。测试将在 创新的数字微流控分析仪，包括样品处理时间在内的总结果时间不到2 小时本研究的产品符合RFA-DA-19-019的目标，即开发“识别 并治疗暴露于阿片类药物的新生儿”，并将进一步支持美国医学会的目标。 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， 缓解急性戒断症状，改善家庭/产妇支助服务的转诊。