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 Feeding intolerance develops in 75% of very low birth weight preterm infants leading to malnutrition and poor 2 neurodevelopmental outcomes. Non-specific signs of developmental feeding intolerance (DFI) are often 3 incorrectly interpreted as pathologic feeding intolerance (PFI); as a result, frequent feeding delays and 4 interruptions lead to prolonged use of parenteral (intravenous) nutrition and central catheters, increasing 5 morbidity in infants who do not have gastrointestinal pathology. This proposal seeks to provide evidence for 6 objective biomarkers to differentiate DFI from PFI with the goal of limiting unnecessary feeding delays, parenteral 7 nutrition, and improving outcomes.