A three-dimensional mathematical and computational model of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a severe disease that affects the gastrointestinal (GI) tract of premature infants. Different areas of NEC research have often been isolated from one another and progress on the role of the inflammatory response in NEC, on the dynamics of epithelial layer healing, and on the positive effects of breast feeding have not been synthesized to produce a more integrated understanding of the pathogenesis of NEC. We seek to synthesize these areas of research by creating a mathematical model that incorporates the current knowledge on these aspects. Unlike previous models that are based on ordinary differential equations, our mathematical model takes into account not only transient effects but also spatial effects. A system of nonlinear transient partial differential equations is solved numerically using cell-centered finite differences and an explicit Euler method. The model is used to track the evolution of a prescribed initial injured area in the intestinal wall. It is able to produce pathophysiologically realistic results; decreasing the initial severity of the injury in the system and introducing breast feeding to the system both lead to healthier overall simulations, and only a small fraction of epithelial injuries lead to full-blown NEC. In addition, in the model, changing the initial shape of the injured area can significantly alter the overall outcome of a simulation. This finding suggests that taking into account spatial effects may be important in assessing the outcome for a given NEC patient. This model can provide a platform with which to test competing hypotheses regarding pathological mechanisms of inflammation in NEC, suggest experimental approaches by which to clarify pathogenic drivers of NEC, and may be used to derive potential intervention strategies.