Predicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy

项目摘要：孕妇阿片类药物使用障碍(OUD)，新生儿阿片类药物戒断综合征 (现在)和相关的医院费用在过去十年里急剧增加，有一个美国孩子 出生时每15分钟就会患上一次新月症。正在进行的阿片类药物流行因COVID而进一步恶化- 19大流行。尽管使用丁丙诺啡或美沙酮进行药物治疗，但孕妇 继续处于早期复发、使用多种物质、过量服药、抑郁、预后不良的高风险，以及 住院时间较长的相关高成本，及其对妇女和妇女的重大负面长期影响 孩子们。母亲的抑郁和焦虑增加了OUD、母亲复发和NOWS的风险。儿童 患有NOWS的患者也有较差的神经发育和行为结局。遗传因素 影响与阿片类药物相关的不良事件和结果，包括OUD和NOWS。当前的临床实践 对于孕妇和NOWS的OUD治疗，不包括主动的风险预测和预防。那里 没有全面和多基因的临床可采用的风险预测工具来主动识别风险 产妇复发、NOWS和昂贵的护理。临床上迫切需要一种可靠的技术，但尚未得到满足 主动预测母体复发和NOWS，并提高妊娠合并尿毒症孕妇的安全性 孩子们。我们已经表明，阿片类药物相关的不良临床结果因潜在的遗传因素而有很大差异。 性情。单基因变异与OUD、NOWS和个体间独立相关 治疗OUD的常用阿片类药物丁丙诺啡、美沙酮和吗啡的反应差异 孕妇和婴儿中的NOWS。OpalGenix将建立在我们之前广泛的前瞻性研究的基础上 阿片类药物相关不良后果的遗传和临床预测因子开发和商业化 设备，OpalGenix的阿片类药物基因导引医生支持，GPS-OpioidTM。GPS-阿片类药物将成为 510(K)批准预测分析软件作为一种医疗设备，由多基因、临床风险因素和 电子健康记录-集成智能分析，提供个性化风险分析以主动预测 包括母亲复发和NOWS在内的OUD相关风险的高准确性(&gt；80%)以启用 个性化干预，显著改善临床结果，同时降低护理成本。在此阶段I 提议，OpalGenix将在这些研究的基础上开发和验证GPS阿片类药物作为510(K)清除算法 (医疗设备)创新性地将多基因和临床风险(例如，产妇抑郁)结合在一起 主动预测母亲复发和NOWS的个性化风险。我们将利用我们团队的专业知识 阿片类药物基因组学，母体OUD，NOWS，组合风险预测算法和 商业化以减轻孕妇及其子女的相关负担。完成这一阶段 I计划将证明GPS阿片类药物在改善临床和经济结果方面的价值，支持FDA 研究设备豁免(IDE)应用，并降低第二阶段面对面临床试验的风险。

PROJECT SUMMARY: Opioid Use Disorder (OUD) in pregnant women, Neonatal Opioid Withdrawal Syndrome (NOWS) and associated hospital costs have dramatically increased in the past decade, with an American child is born suffering from NOWS every 15 minutes. The ongoing opioid epidemic is further worsened by the COVID- 19 pandemic. Despite medication treatment for OUD with buprenorphine or methadone, the pregnant women continue to be at high risk for early relapse, polysubstance use, overdose, depression, poor outcomes, and associated high costs of longer hospital stays, and their significant negative long-term effects in women and their children. Maternal depression and anxiety increase the risks for OUD, maternal relapse and NOWS. Children with NOWS also experience poor long-term neurodevelopmental and behavioral outcomes. Genetic factors influence opioid-related adverse events and outcomes including OUD and NOWS. The current clinical practices for OUD treatment in pregnant women and NOWS do not include proactive risk prediction and prevention. There is no comprehensive and polygenetic clinically adoptable risk prediction tool to proactively identify risks for maternal relapse, NOWS and costly care. There is an urgent and unmet clinical need for a reliable technology to proactively predict maternal relapse, NOWS, and improve the safety of pregnant women with OUD and their children. We have shown that opioid related poor clinical outcomes vary significantly based on underlying genetic predisposition. Single gene variations are independently associated with OUD, NOWS and inter-individual variations in responses to buprenorphine, methadone and morphine, the commonly used opioids to treat OUD in pregnant women and NOWS in infants. OpalGenix will build on our extensive prior prospective studies of genetic and clinical predictors of opioid-related adverse outcomes to develop and commercialize a transformative device, OpalGenix’s Genotype-guided Physician Support for Opioids, GPS-OpioidTM. GPS-Opioid will be a 510(k) cleared predictive analytic software as a medical device consisting of polygenetic, clinical risk factors and electronic health record-integrated intelligent analytics to provide personalized risk analysis to proactively predict risk for OUD-related risks including maternal relapse and NOWS with high accuracy (>80%) to enable personalized interventions, significantly improve clinical outcomes while reducing costs of care. In this Phase I proposal, OpalGenix will build on these studies to develop and validate GPS Opioid as a 510(k) cleared algorithm (medical device) that innovatively integrates polygenetic and clinical risks (e.g., maternal depression) to proactively predict personalized risk for maternal relapse and NOWS. We will leverage our team’s expertise with opioid pharmacogenomics, maternal OUD, NOWS, combinatorial risk predictive algorithms and commercialization to reduce OUD related burden in pregnant women and their children. Completion of this Phase I program will demonstrate value for GPS Opioid to improve clinical and economic outcomes, support an FDA Investigational Device Exemption (IDE) application, and de-risk a Phase II head-to-head clinical trial.