Necrotizing enterocolitis: A multifactorial disease with no cure

Table 1 Bell’s staging criteria for necrotizing enterocolitis

Stage	Systemic signs	Intestinal signs	Radiological signs
IA (Suspected)	Temperature instability, apnea, bradycardia, lethargy	Poor feeding, emesis, ↑ pre-gavage residuals, mild abdominal distension	Normal or intestinal dilation, mild ileus
IB (Suspected)	Same as above	Above and blood from rectum	Same as above
IIA (Proven)	Same as above	Above + absent bowel sounds + mild abdominal tenderness	Intestinal dilation, ileus, pneumatosis intestinalis
IIB (Proven)	Above + metabolic acidosis + thrombocytopenia	Above + definite abdominal tenderness	Above + portal vein gas + possible ascites
IIIA (Advanced)	Above + hypotension, respiratory acidosis, neutropenia	Above + peritonitis, marked distension of abdomen	Above + definite ascites
IIIB (Advanced)	Same as above	Same as above	Above + pneumoperitoneum

Table 2 Ischemic events associated with necrotizing enterocolitis

Perinatal asphyxia

Polycythaemia

Cyanotic congenital heart disease

Patent ductus arteriosis

Medications that ↓ superior mesenteric blood flow (cocaine)

Maternal pre-eclampsia

Table 3 Eicosanoid synthesis and actions

Eicosanoid	Cell/tissue origin	Target cell/tissue	Receptor	Action
PGE2	Most cells	Many cells	EP1-EP4	Fever, pain
PGI2	Endothelium	Platelet VSMC	IP	Declumping, vasodilation
PGF2	Uterus	Uterine SMC	FP	Contraction
PGD2	Mast cells	Lung Th2 cells	DP1/DP2	Asthma, chemotaxis
TXA2	Platelets	Platelet VSMC	TPα/TPβ	Aggregation, vasoconstriction
LTB4	Macrophage monocytes	Neutrophils	BLT1/BLT2	Promotes chemotaxis
LTC4/LTD4/LTE4	Macrophage monocytes	Lung SMC	BLT3/BLT4	Bronchoconstriction
LXA4	Leukocytes	Neutrophil	LXA4 R	Inhibits chemotaxis
LXB4	Leukocytes	NK cells	?	Inhibits cytotoxicity

Table 4 Strategies to prevent necrotizing enterocolitis

Evidence-based support for efficacy	Limited data to support efficacy
Breast feeding	Cautious advancement of feedings
Trophic feeding	Fluid restriction
Antenatal steroids	Oral immunoglobulins
Enteral administration of antibiotics	L-arginine supplementation
	Polyunsaturated fatty acids
	Acidification of milk feeds
	Probiotics, prebiotics and postbiotics
	Growth factors and erythropoietin
	Free radical scavengers