Integrating Novel Physiological Biomarkers of Feeding Intolerance in Preterm Infants

整合早产儿喂养不耐受的新型生理生物标志物

• 批准号: 10739943
• 负责人: Eric Brum Ortigoza
• 金额: $ 16.74万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739943
• 关键词: 16S ribosomal RNA sequencing; Abdomen; Address; Age; Area; Bioinformatics; Biological Markers; Blinded; Catheters; Child Health; Clinical; Clinical Research; Collection; Complex; Computer Models; Cutaneous; Data; Dedications; Development; Development Plans; Enteral Feeding; Environment; Feces; Fostering; Foundations; Funding; Gastrointestinal Motility; Gastrointestinal Physiology; Goals; Growth; Health; Hospitals; Ileus; Infant; Interruption; Intestinal Obstruction; Intestinal Perforation; Intravenous; K-Series Research Career Programs; Knowledge; Lead; Leadership; Learning; Length of Stay; Longitudinal cohort study; Machine Learning; Malnutrition; Master of Science; Measurement; Measures; Medical center; Mentors; Mesentery; Methods; Monitor; Morbidity - disease rate; Multicenter Studies; Near-Infrared Spectroscopy; Necrotizing Enterocolitis; Neonatal; Neonatal Intensive Care; Neonatal Intensive Care Units; Outcome; Parenteral Nutrition; Pathologic; Pathology; Physicians; Physiological; Pregnancy; Premature Infant; Principal Component Analysis; Productivity; Prospective, cohort study; Proteobacteria; Research; Research Personnel; Risk; Sample Size; Shotguns; Signal Transduction; Stomach; System; Taxonomy; Testing; Time; Training; Validation; Very Low Birth Weight Infant; Volatile Fatty Acids; Work; age related; biomarker development; biomarker validation; career development; cell motility; commensal bacteria; commensal microbes; evidence base; feeding; gastrointestinal; gut microbiome; gut microbiota; high throughput analysis; improved outcome; innovation; metabolomics; microbiome; microbiota; microbiota metabolites; motility disorder; multidisciplinary; novel; nutrition; operation; patient population; perinatal medicine; predictive modeling; prevent; programs; prospective; recruit; segregation; skills; skills training; stool sample; tool; translational medicine

1 Eric B. Ortigoza, MD, MSCR is a Neonatal-Perinatal Medicine physician with a Master of Science in Clinical 2 Research at UT Southwestern Medical Center (UTSW). His goal is to be an independently funded investigator 3 with expertise in neonatal gastrointestinal motility. He plans to investigate novel, comprehensive objective 4 methods to differentiate developmental feeding intolerance (DFI) from pathologic feeding intolerance (PFI) with 5 the goal of limiting unnecessary feeding delays, parenteral nutrition, and improving outcomes in preterm infants. 6 In a prospective, longitudinal cohort study, preterm infants who are born <32 weeks’ gestation will undergo 7 weekly non-invasive electrogastrography (EGG), abdominal near-infrared spectroscopy (aNIRS), and stool 8 collection. Dr. Ortigoza’s specific aims are to 1) quantify postmenstrual age-dependent differences in non- 9 invasive continuous gastrointestinal monitoring in preterm infants with DFI, PFI, and no feeding intolerance (NFI), 10 and 2) measure postmenstrual age-dependent differences in the gut microbiome and microbiota-derived 11 metabolites in preterm infants with DFI, PFI, and NFI. Dr. Ortigoza’s innovative approach integrates objective 12 gastrointestinal biomarkers of gastric motility, mesenteric oxygenation, bacterial colonization, and microbiota- 13 derived metabolites to differentiate DFI from PFI. The ability to differentiate between the two conditions will 14 encourage the development of predictive models for PFI in preterm infants using bioinformatics and machine 15 learning. The ability to predict PFI will help develop evidence-based strategies aimed at preventing and/or 16 treating episodes of PFI. Dr. Ortigoza has assembled a multidisciplinary team of mentors with expertise in the 17 key areas of computational modeling of complex physiological variables (Lina Chalak, MD, MSCS), advanced 18 gut microbiome profiling (Andrew Koh, MD and Julie Mirpuri, MD), and metabolite analysis (Andrew Koh, MD). 19 UTSW and its strong clinical research operation provide the ideal environment to conduct the proposed studies 20 with the large patient population at Parkland Health and Hospital System (PHHS) and Children’s Health, a 21 dedicated Center for Translational Medicine, and a strong record of clinical research participation. Dr. Ortigoza’s 22 Career Development Plan includes a comprehensive focused strategy to address the specific key training skills 23 that will allow him to transition to independence including: 1) developing expertise in complex signal analysis of 24 EGG and aNIRS data, 2) gaining expertise in interpretation of high throughput analysis of the gut microbiome 25 and its derived metabolites, and 3) developing expertise in biomarker development/validation. In addition, he will 26 receive training to develop leadership skills that are critical to fostering a productive research team and building 27 a successful research program. Together with his scientific aims, these goals will provide the skills necessary 28 for Dr. Ortigoza to build his independent research program in neonatal gastrointestinal motility.

1埃里克B。Ortigoza，医学博士，MSCR是一名新生儿围产期医学医生，拥有临床医学硕士学位 2 UT西南医学中心（UTSW）研究。他的目标是成为一名独立资助的调查员 3名具有新生儿胃肠动力学专业知识。他计划调查小说，全面客观 4种区分发育性喂养不耐受（DFI）和病理性喂养不耐受（PFI）的方法， 5限制不必要的喂养延迟、肠外营养和改善早产儿结局的目标。 6在一项前瞻性、纵向队列研究中，妊娠<32周出生的早产儿将接受 每周7次无创胃电描记术（EGG）、腹部近红外光谱（aNIRS）和粪便 8收藏。Ortigoza博士的具体目标是：1）量化经后年龄依赖性的非 9例患有DFI、PFI和无喂养不耐受（NFI）的早产儿的有创连续胃肠道监测， 10和2）测量月经后肠道微生物组和微生物来源的年龄依赖性差异 患有DFI、PFI和NFI的早产儿中的11种代谢物。Ortigoza博士的创新方法整合了客观 胃动力、肠系膜氧合、细菌定植和微生物群的12种胃肠道生物标志物- 13种衍生代谢物以区分DFI和PFI。区分这两种情况的能力将 14鼓励使用生物信息学和机器开发早产儿PFI的预测模型 15学习预测PFI的能力将有助于制定以证据为基础的战略，旨在预防和/或 16次治疗PFI发作。Ortigoza博士组建了一个多学科的导师团队， 复杂生理变量计算建模的17个关键领域（Lina Chalak，MD，MSCS），高级 18肠道微生物组分析（Andrew Koh，MD和Julie Mirpuri，MD）和代谢物分析（Andrew Koh，MD）。 19. UTSW及其强大的临床研究运作为开展拟议研究提供了理想的环境 帕克兰健康和医院系统（PHHS）和儿童健康的大量患者， 21个专门的转化医学中心，并有很强的临床研究参与记录。Ortigoza医生 22职业发展计划包括一个全面的重点战略，以解决具体的关键培训技能 23，这将使他过渡到独立，包括：1）发展复杂信号分析的专业知识， 24 EGG和aNIRS数据，2）获得解释肠道微生物组高通量分析的专业知识 25及其衍生代谢物，和3）发展生物标志物开发/验证的专业知识。另外他还会 26人接受培训，以发展领导技能，这对培养一支富有成效的研究团队和建立 27、一个成功的研究项目。连同他的科学目标，这些目标将提供必要的技能， 28 Ortigoza博士建立他的新生儿胃肠动力独立研究计划。