Predictors of Neonatal Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is primarily a disease process of the gastrointestinal tract of neonates that results in inflammation and bacterial invasion of the bowel wall.

Despite extensive research, the pathophysiology of NEC remains unclear and therapeutic options are limited.

Clinical manifestations of NEC may be vague, including increased episodes of apnea, desaturations, bradycardia, lethargy and temperature instability.

There may also be GI-specific symptoms such as feeding intolerance, emesis, bloody stools, abdominal distention and tenderness, and abdominal wall discoloration.

Radiographic signs may include ileus, dilated or fixed intestinal loops, air in the intestinal wall or free air in the abdomen.

NEC diagnosis, however, remains challenging because many now see that Bell's staging criteria currently used for diagnosis as being not accurate.

Neutrophil to lymphocyte ratio (NLR) is used as a marker of subclinical inflammation. It is calculated by dividing the number of neutrophils by number of lymphocytes, usually from peripheral blood sample. Increase of neutrophil proportion just reflects the deterioration of the immune system, while decreased lymphocyte ratio reflects the increasing level of physical stress.

Further NLR is closely related to the inhibition of body's immune function. In a word, NLR could indicate the status of body's inflammation response and the level of physical stress timely and accurately.

In a clinical study conducted in 2001, the authors suggested the routine use of NLR as a stress factor in clinical ICU practice, and they claimed that NLR might has a prognostic and a predictive value of many diseases.

Gamma glutamyl transferase (GGT) is an enzyme found in the cell membranes of many tissues. The highest concentration is in the kidney, but the liver is considered the source of normal enzyme activity. GGT is involved in the transfer of amino acids across the cell membrane and also in leukotriene metabolism. It has an intracellular antioxidant effect because it is involved in glutathione metabolism, resulting in the formation of cysteine. GGT is cleared from the plasma by liver uptake.

Bilirubin is a free radical scavenger with anti-inflammatory and antioxidant property. One report described that stage III NEC had lower total serum bilirubin than their mild or disease-free controls during the first 14 days of life. Since serum bilirubin level is a function of the activity of UGT1A1, albumin binding, and the bilirubin load; it will be important to determine if serum bilirubin concentration correlates with NEC development or severity.

A relatively constant serum calcium (Ca2+) concentration is vital for cellular function and under strict control by the neural/humoral factors. It is unclear what causes serum Ca2+ lower in NEC neonates. In a recent report, higher level of serum GGT, a significantly lower serum bilirubin and Ca2+ were found in severe NEC.

Inclusion criteria

• Patient group: NEC preterm neonates with gestational ages are between 28-36 weeks regardless of birth weight. NEC diagnosis and staging will be according to Bell's staging criteria.

• Control group: Stable preterm neonate with matched gestational and postnatal ages without infectious diseases will be included.

Exclusion criteria

• Neonates with congenital infectious diseases, perinatal asphyxia, severe birth defects, congenital digestive tract malformations, inherited metabolic diseases or parental refusal of enrollment.