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 Eric B. Ortigoza，医学博士，MSCR是新生儿 - 周期医学实物，具有临床科学硕士学位 2在UT西南医疗中心（UTSW）的研究。他的目标是成为一名独立资助的调查员 3具有新生儿胃肠道运动的专业知识。他计划调查新颖，全面的目标 与病理喂养肠道（PFI）区分发育进食intlance（DFI）的4种方法 5限制不必要的喂养延迟，父母营养以及改善早产儿的预后的目的。 6在一项前瞻性的纵向队列研究中，出生的早产儿将接受妊娠<32周 每周7个非侵入性电阵线学（EGG），腹部近红外光谱（Anirs）和凳子 8集合。 Ortigoza博士的具体目的是1）量化非属性后年龄依赖性差异 9在患有DFI，PFI和无喂养intlerance（NFI）的早产儿中，侵入性连续胃肠道监测， 10和2）测量肠道微生物组和微生物衍生的月经后依赖年龄的差异 DFI，PFI和NFI的早产儿中的11个代谢产物。 Ortigoza博士的创新方法整合了目标 12胃运动，肠系膜氧合，细菌定殖和微生物群的胃肠道生物标志物 13衍生的代谢产物将DFI与PFI区分开。区分两个条件的能力将 14鼓励使用生物信息学和机器在早产儿中开发PFI的预测模型 15学习。预测PFI的能力将有助于制定旨在防止和/或 16处理PFI的发作。 Ortigoza博士已经组建了一个具有专业知识的多学科导师团队 17复杂生理变量（Lina Chalak，MD，MSC）的计算建模的关键领域，高级 18肠道微生物组分析（医学博士Andrew Koh和MD）和代谢物分析（Andrew Koh，MD）。 19 UTSW及其强大的临床研究操作提供了进行拟议研究的理想环境 20在帕克兰健康与医院系统（PHHS）和儿童健康的患者人口众多， 21专门的转化医学中心，以及临床研究参与的强大记录。 Ortigoza博士 22职业发展计划包括一项全面的集中策略，以解决特定的关键培训技能 23这将使他能够过渡到独立性，包括：1）在复杂信号分析中培养专业知识 24鸡蛋和贫血数据，2）在解释肠道微生物组的高吞吐量分析方面获得专业知识 25及其衍生的代谢产物，以及3）发展生物标志物开发/验证方面的专业知识。此外，他会 26接受培训以发展领导技能，这对于培养富有成效的研究团队至关重要 27成功的研究计划。以及他的科学目标，这些目标将提供必要的技能 28 Ortigoza博士在新生儿胃肠道运动中构建他的独立研究计划。