728 - Early Urinary Inflammatory Biomarkers for Necrotizing Enterocolitis and Spontaneous Intestinal Perforation Among Extremely Premature Neonates

Publication Number: 728.4935

Michelle Hojnicki, Johns Hopkins All Children's Hospital - 501 6th Ave SSt. Petersburg, FL 33701UNITED STATES - St. Pe, Palmetto, FL, United States; Steven Bruzek, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, United States; Vera Ignjatovic, Johns Hopkins All Children's Hospital Institute for Clinical and Translational Research, St. Petersburg, FL, United States; Frank W. Ayestaran Cassani, USF Health Morsani College of Medicine, st petersburg, FL, United States; Anthony A. Sochet, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States; Rita Wyrebek, SSM Health Cardinal Glennon Children's Hospital / Saint Louis University, Saint Louis, MO, United States

Background: Identifying noninvasive biomarkers for necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) among extremely premature neonates is a research priority.

Objective: To characterize and compare the urine targeted inflammatory profile in a cohort of extremely premature neonates who did and did not go on to develop NEC/SIP.

Design/Methods: We performed a secondary analysis of stored specimens from 24 neonates < 28 weeks gestational age (GA) collected serially in the postnatal transitional period at: < 12 hours, at 24 hours, at 48 hours, and 72 hours of life. Targeted proteomics (Olink® Target 48 Cytokine proximity extension assay, corrected for urine creatinine) was performed as a pooled analysis, by sample collection times, groups who did and did not developNEC/SIP. Demographics, anthropometrics, treatments, and clinical outcomes were collected. Descriptive, comparative, and receiver operator characteristics (ROC) curve analyses were employed.

Results: A total of 24 unique encounters were studied of which 8 (33%) developed NEC and/or SIP. A total of 74 samples were analyzed (n=10 at 12-hours, n=18 at 24-hours, n=23 at 48-hours, and n=23 at 72-hours). The mean GA was 25.3±1.5 weeks and birthweight was 755±214 grams. Pooled analysis (n=49 without NEC/SIP vs n=25 with NEC/SIP, respectively) from all timepoints observed the following significantly different urinary analytes: oxidized low density lipoprotein receptor 1 (OLR1): 73.7±58.7 pg:ml/mg/dL vs 47.2±46.8 pg:ml/mg/dL (p=0.039), tumor necrosis factor superfamily member 12 (TNFSF12): 14.3±14.1 pg:ml/mg/dL vs 7.4±6.2 pg:ml/mg/dL (p < 0.001), hepatocyte growth factor (HGF): 133±272.8 pg:ml/mg/dL vs 40.6±18.2 pg:ml/mg/dL (p=0.02), and interleukin-15 (IL15): 3.5±2.7 pg:ml/mg/dL vs 2.5±1.4 pg:ml/mg/dL (p=0.041). The area under the ROC curves were notable for OR1 (0.69 [95%CI: 0.57-0.79]) and TNFSF12 (0.63 [95%CI: 0.52-0.74]). Cytokines and chemokines that were detectably different for those with and without NEC/SIP at other study timepoint comparisons during the transitional period included OLR1, TNFSF12, IL15, matrix metalloproteinase 12 (MMP12), and fms-related receptor tyrosine kinase 3 ligand (FLT3LG).

Conclusion(s): Among extremely premature infants, we identified several urinary protein biomarkers for NEC/SIP that require future validation and mechanistic exploration.