Low Abdominal NIRS Values and Elevated Plasma Intestinal Fatty Acid-Binding Protein in a Premature Piglet Model of Necrotizing Enterocolitis

• Published in: PloS one Vol. 10; no. 6; p. e0125437
• Main Authors: Zamora, Irving J, Stoll, Barbara, Ethun, Cecilia G, Sheikh, Fariha, Yu, Ling, Burrin, Douglas G, Brandt, Mary L, Olutoye, Oluyinka O
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.06.2015; Public Library of Science (PLoS)
• Subjects: Abdomen; Animals; Birth weight; Diagnostic software; Diagnostic systems; Disease Models, Animal; Enterocolitis; Enterocolitis, Necrotizing - metabolism; Enzyme-linked immunosorbent assay; Euthanasia; Fatty acid-binding protein; Fatty Acid-Binding Proteins - metabolism; Fatty acids; Gastrointestinal diseases; Heart rate; Hogs; Hospitals; I.R. radiation; Infrared spectra; Infrared spectroscopy; Intestine; Ischemia; Laboratory animals; Medicine; Mortality; Near infrared radiation; Near infrared spectroscopy; Necrosis; Necrotizing enterocolitis; Neonates; Newborn babies; Nutrition; Nutrition research; Oxygen; Oxygen content; Parenteral nutrition; Pediatrics; Physiology; Plasma; Protein binding; Proteins; Saturation; Sensitivity; Serum Amyloid A Protein - metabolism; Spectroscopy, Near-Infrared - methods; Spectrum analysis; Surgery; Swine; Variability; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125437

To identify early markers of necrotizing enterocolitis (NEC), we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS) measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP) measured every 6 hours can detect NEC prior to onset of clinical symptoms. Premature piglets received parenteral nutrition for 48-hours after delivery, followed by enteral feeds every three hours until death or euthanasia at 96-hours. Continuous A-NIRS, systemic oxygen saturation (SpO2), and heart rate were measured while monitoring for clinical signs of NEC. Blood samples obtained at 6-hour intervals were used to determine pI-FABP levels by ELISA. Piglets were classified as fulminant-NEC (f-NEC), non-fulminant-NEC (nf-NEC) and No-NEC according to severity of clinical and histologic features. Of 38 piglets, 37% (n=14) developed nf-NEC, 18% (n=7) developed f-NEC and 45% (n=17) had No-NEC. There were significant differences in baseline heart rate (p=0.008), SpO2 (p<0.001) and A-NIRS (p<0.001) among the three groups. A-NIRS values of NEC piglets remained lower throughout the study with mean for f-NEC of 69±3.8%, 71.9±4.04% for nf-NEC, and 78.4±1.8% for No-NEC piglets (p<0.001). A-NIRS <75% predicted NEC with 97% sensitivity and 97% specificity. NEC piglets demonstrated greater variability from baseline in A-NIRS than healthy piglets (10.1% vs. 6.3%; p=0.04). Mean pI-FABP levels were higher in animals that developed NEC compared to No-NEC piglets (0.66 vs. 0.09 ng/mL;p<0.001). In f-NEC piglets, pI-FABP increased precipitously after feeds (0.04 to 1.87 ng/mL;p<0.001). pI-FABP levels increased in parallel with disease progression and a value >0.25ng/mL identified animals with NEC (68% sensitivity and 90% specificity). NIRS is a real-time, non-invasive tool that can serve as a diagnostic modality for NEC. In premature piglets, low A-NIRS in the early neonatal period and increased variability during initial feeds are highly predictive of NEC, which is then confirmed by rising plasma I-FABP levels. These modalities may help identify neonates with NEC prior to clinical manifestations of disease.