The pathophysiology of necrotizing enterocolitis in preterm infants
Necrotizing enterocolitis (NEC) is a severe gastrointestinal disorder affecting the preterm infant. The underlying cause of NEC is partly unknown. In this thesis we studied the gut flora, the intestinal barrier function, and the intestinal blood circulation contributing to NEC.
We observed NEC-associated bacteria (Clostridium perfringens and Bacteroides dorei) in the first baby poop after birth (meconium). These bacteria might predispose the intestine to an early inflammatory reaction. We also observed an increase of immune competent Paneth cells, the guardians of the deepest regions of the gut (crypts), from a gestational age of 29 weeks onwards, which is the same postmenstrual age when NEC commonly develops.
This combination of NEC-associated bacteria and the increase of Paneth cells probably stimulates the inflammatory reaction, which damages the surrounding intestinal cells sometimes leading to necrosis of the bowel wall. Furthermore, the preterm infant often has a diminished intestinal blood circulation (e.g. due to low blood pressure). The diminished intestinal blood circulation decreases the amount of oxygen reaching the intestinal cells which further stimulates damage of these cells and could contribute to necrosis. Indeed, we observed a diminished intestinal blood circulation during NEC (measured via near-infrared spectroscopy (NIRS)). Damage of the bowel wall (measured via the marker I-FABP) was related to (the severity of) NEC, the severity of diminishing of intestinal blood circulation, and the length of intestinal necrosis in (surgical) NEC.
The occurrence of NEC thus seems to be a complex interplay between local inflammation of the intestines, NEC-associated bacteria, and a diminished intestinal blood circulation.