**12. Prevention**

Prevention is the primary strategy in this devastating disease with undetermined etiology. Breast milk feeding, prolonging gestation to avoid prematurity, antenatal steroid, and the use of probiotics/prebiotics are established prevention strategies in NEC [16]. Nonaggressive feeding is evidenced to be efficacious. The rate of advancement of feeding under 20 ml/kg/day is considered to be safe. Newer strategies, such as use of toll-like receptor agonist, glutamine, n-3 fatty acids, anti-cytokines, and growth factors are proposed preventive interventions, but most of these either lack evidence or have questionable safety. Compound CpG-DNA inhibit TLR4 signaling, thereby dramatically reducing the severity of NEC in mice. Clinically, the following measures are suggested to be practiced in order to reduce the risk of NEC: human milk (both mother's and donor's); standardized feeding guidelines, including early initiation with trophic feeds; the use of probiotics; antibiotic stewardship; optimization of enteral nutrition and growth; elimination of H2 blockers and acid pump suppressors; elimination of cow's milk products; transfusion protocols; and transfusion outcome monitoring. Avoidance of hyperosmolar agents, treatment of polycythemia, and delayed cord clamping are other interventions that are suggested to be followed. Prophylactic probiotics, although not yet universally applied due to uncertainties about its dose and duration of therapy, have been documented to reduce the incidence of NEC, especially that of severe cases (RR 0.75 95% CI −0.57 to 0.92) in infants <1500 g in multiple studies [64]. There are concerns about bacteremia and some aspects of quality control which restrict its use.
