A weighted and cumulative point system for accurate scoring of intestinal pathology in a piglet model of necrotizing enterocolitis

Abstract

AbstractBackgroundNecrotizing enterocolitis (NEC) is a serious condition, primarily affecting premature infants, in which a portion of the gut undergoes inflammation and necrosis. Symptoms of NEC are unspecific, and together with a rapid progression, the disease remains a significant concern. The preterm pig develops NEC spontaneously, making it a suitable model for exploring novel treatments. During piglet necropsy, NEC-lesions closely resemble the pathologies found during surgery or autopsy of preterm infants. As such, the systematic gross inspection enables direct evaluation of gut lesions, which is not possible in the medical preterm patient. Here, we introduce a revised intestinal scoring system with an expanded score range and more detailed descriptive features to accurately describe the diversity of NEC-lesions in the preterm piglet model.MethodsWe included 333 preterm piglets from four separate experiments, each delivered via cesarian section at 90% gestation. The pigs were fed either a gently processed (GP) or harshly processed (HP) milk formula for 96 hours and were subsequently euthanized. At necropsy, the gastrointestinal tract was assessed with 1) an established 6-grade scoring system and 2) a systematic and descriptive approach focusing on the distribution and severity of hyperemia, hemorrhage, pneumatosis intestinalis (intramural gas), and necrosis. Lesion biopsies were sampled for cytokine measurement and a subset (n= 62) was sampled for histopathological assessment.ResultsThe systematic and descriptive registrations were evaluated and converted into a weighted and cumulative point (WCP) score. Compared to the 6-grade score, the WCP score enabled a higher discrepancy in severity levels, especially among organs with more prominent NEC lesions. IL-1β in small intestinal lesions and both IL-8 and IL-1β in colon lesions correlated positively with the WCP scale. A histopathological grade system (0-8) was established and revealed mucosal lesions not recognized macroscopically. Finally, the WCP score showed a higher NEC-promoting effect of the HP formula compared to the GP formula.ConclusionThe validation of the weighted and cumulative scoring system demonstrated an expanded score range, enhancing the accuracy in describing NEC-lesions in gastrointestinal segments of preterm pigs. This approach may increase the efficiency of preclinical NEC experiments.