Predictors of Neonatal Necrotizing Enterocolitis

Necrotising Enterocolitis Clinical Trial

Official title:

Evaluation of Some Blood Biomarkers as Predictors of Neonatal Necrotizing Enterocolitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04277533
• Other study ID #: necrotizing enterocolitis
• Status: Completed
• Start date: June 15, 2019
• Est. completion date: February 15, 2020

Study information

• Verified date: August 2020
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To assess the value of peripheral blood neutrophil to lymphocyte ratio (NLR), serum levels of γ-Glutamyl transferase (GGT), total serum bilirubin and serum calcium (Ca2+) concentrations for early diagnosis and prediction of NEC severity and if found significant, scoring will be done according to their levels in different Bell's stages.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: February 15, 2020
• Est. primary completion date: December 15, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 30 Days

Eligibility

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.

Related Conditions & MeSH terms

• Enterocolitis
• Enterocolitis, Necrotizing
• Necrotising Enterocolitis

Intervention

Diagnostic Test:
• Serum ?-Glutamyl transferase (GGT), Total serum bilirubin (TSB), Serum calcium concentration (Ca2+), Peripheral blood neutrophil to lymphocyte ratio (NLR)
GGT, Ca2+, NLR and TSB are serum markers which had been studied for early detection and prediction of severity of NEC.

Locations

Country	Name	City	State
Egypt	Ain Shams university Faculty of medicine	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (18)

Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978 Jan;187(1):1-7. — View Citation

Cabrera-Abreu JC, Green A. Gamma-glutamyltransferase: value of its measurement in paediatrics. Ann Clin Biochem. 2002 Jan;39(Pt 1):22-5. Review. Erratum in: Ann Clin Biochem. 2002 May;39(Pt 3):323. — View Citation

de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care. 2010;14(5):R192. doi: 10.1186/cc9309. Epub 2010 Oct 29. — View Citation

Fereshtehnejad SM, Poorsattar Bejeh Mir K, Poorsattar Bejeh Mir A, Mohagheghi P. Evaluation of the possible antioxidative role of bilirubin protecting from free radical related illnesses in neonates. Acta Med Iran. 2012;50(3):153-63. — View Citation

Gordon PV, Swanson JR, Attridge JT, Clark R. Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's criteria? J Perinatol. 2007 Nov;27(11):661-71. Epub 2007 Jul 5. Review. — View Citation

Han CQ and Wei XY (2017): Novel biomarkers to determine neonates with necrotizing enterocolitis, Biomedical Research; 28 (13): 6002-6006.

Levitt DG, Levitt MD. Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease. Clin Exp Gastroenterol. 2014 Sep 2;7:307-28. doi: 10.2147/CEG.S64283. eCollection 2014. Review. — View Citation

Li B, Zhang ZL, Yang ZZ, Zhang HZ. (2012): Application value of neutrophil and lymphocyte count ratio in respiratory tract infectious diseases. Zhong Guo Xue Ye Liu Bian Xue Za Zhi; 22: 522-524. In Chinese.

Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet. 2006 Oct 7;368(9543):1271-83. Review. — View Citation

Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science. 1987 Feb 27;235(4792):1043-6. — View Citation

Terrin G, Stronati L, Cucchiara S, De Curtis M. Serum Markers of Necrotizing Enterocolitis: A Systematic Review. J Pediatr Gastroenterol Nutr. 2017 Dec;65(6):e120-e132. doi: 10.1097/MPG.0000000000001588. Review. — View Citation

Thompson AM, Bizzarro MJ. Necrotizing enterocolitis in newborns: pathogenesis, prevention and management. Drugs. 2008;68(9):1227-38. Review. — View Citation

Yajamanyam PK, Rasiah SV, Ewer AK. (2014): Necrotizing enterocolitis: current perspectives, Dove Medical Press Limited, Volume 2014:4 Pages 31-42

Yang M, Li L, Su N, Lin J, Wang J. [Dynamic monitoring of the neutrophil/lymphocyte ratio could predict the prognosis of patients with bloodstream infection]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015 Jun;27(6):471-6. doi: 10.3760/cma.j.issn.2095-4352.2015.06.011. Chinese. — View Citation

Yang Y, Cao ZL, Zhou XY, Chen XQ, Pan JJ, Cheng R. Does neutrophil/lymphocyte ratio have good diagnostic value in neonatal necrotizing colitis? J Matern Fetal Neonatal Med. 2019 Sep;32(18):3026-3033. doi: 10.1080/14767058.2018.1455182. Epub 2018 Mar 27. — View Citation

Yokoyama H. [Gamma glutamyl transpeptidase (gammaGTP) in the era of metabolic syndrome]. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2007 Jun;42(3):110-24. Review. Japanese. — View Citation

Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5-14. English, Slovak. — View Citation

Zimmerman K., Daniel K. (2018): Principals and practice of pediatric infectious diseases textbook, Chapter H. Gastrointestinal Tract Infections and Intoxications, necrotizing enterocolitis; page 394-397

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of some blood biomarkers as predictors of neonatal necrotizing enterocolitis.	The peripheral blood neutrophil to lymphocyte ratio (NLR), serum levels of ?-Glutamyl transferase (GGT), total serum bilirubin and serum calcium (Ca2+) concentrations would been studied for early diagnosis and prediction of NEC severity and if found significant, scoring will be done according to their levels in different Bell's stages.	Baseline