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

Abstract

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.

Abdominal near-infrared spectroscopy in a piglet model of gastrointestinal hypoxia produced by graded hypoxia or superior mesenteric artery ligation

“…Adult rabbits had decreased liver oxygenation with SMA occlusion (7). Moreover, lower aNIRS correlated with the development of NEC in premature piglets (6,11). In our model, a significant correlation was evident between the change in aNIRS and the decrease in the perfusion from baseline.…”

“…A previous study in premature piglets reported a difference in aNIRS saturations of 6.5% (standard deviation (SD): 4) between piglets with non-fulminant NEC and those with no NEC (6). Using these estimates, a sample size of seven would reject the null hypothesis that injured and non-injured piglets have similar aNIRS values at an alpha level of 0.05 and power of 0.8.…”

Surgical necrotizing enterocolitis

“…Combining NIRS with other modalities is a currently area of interest. Zamora et al 78 recently hypothesized that continuous abdominal NIRS monitoring combined with plasma I-FABP levels could identify NEC prior to the onset of clinical symptoms in premature piglets. In their study, I-FABP was confirmed to be a sensitive and specific indicator of NEC onset and severity.…”

Early detection of necrotizing enterocolitis using broadband optical spectroscopy

“…described the transabdominal use of neonatal cerebral oximeters in a piglet model of NEC and found on post hoc analysis that low tissue oxygen saturations predicted the development of NEC. [7] In a separate paper from the same group, this finding was confirmed in neonates, though the significance of low saturations occurring days to weeks before the clinical onset of NEC was unclear. [8] Schat et al .…”