Human Intestinal Fatty Acid binding protein as a prognostic marker in premature Neonates suffering from Necrotizing Enterocolitis

Abstract

Necrotizing enterocolitis (NEC) is a severe acute gastrointestinal disease affecting mainly preterm newborns. The pathophysiology of NEC remains poorly understood. The main risk factors of NEC are immaturity of gut barrier and immune system together with enteral feeding and abnormal microbial colonization of the gut. On the other hand, breastfeeding represents an important factor protecting from NEC. Thanks to its unique composition, mother’s milk not only accelerates gut barrier maturation but also protects neonatal gut from infection. The former is achieved mainly by numerous growth factors and the later by antimicrobial factors (e.g., lactoferrin and lysozyme) and by secretory IgA, which could bind microbes in antigen-specific and nonspecific manner by Fab or glycans, respectively. With overall incidence of 1 to 3 cases per 1000 live births and mortality as high as 50%, NEC is one of the leading causes of morbidity and mortality in neonatal intensive care units . The early recognition and proper treatment can, however, improve the clinical outcomes . The current diagnosis of NEC is based on the combination of clinical, laboratory, and radiologic or sonographic findings, which are defined by modified Bell’s staging criteria . But NEC has often rapid onset and progression with nonspecific early signs, which may delay the NEC treatment by misdiagnosing it as neonatal sepsis or other medical emergency. While there are specific signs for NEC, such as pneumatosis intestinalis or gas in the portal vein, they appear rather later in the disease course and their absence must be interpreted with caution . Therefore, the identification of specific biomarkers for early diagnosis of NEC is strongly needed. The best biomarkers should be specific for the early steps in NEC pathogenesis. Since several studies demonstrated the advantages of biomarker combination in the NEC diagnosis, we combined analysis of several noninvasive markers of excessive inflammatory response and destruction of the gut mucosa, all typical features of NEC pathogenesis . Fatty acid-binding proteins (FABPs) are small (14-15 kDa) tissue-specific cytoplasmic proteins involved in the metabolisms of fatty acids. The IFABP constitutes up to 2% of cytoplasmic protein content in the mature enterocyte. Upon the enterocyte death, I-FABP is released into the circulation and thus can be used as a marker of intestinal damage .