Role of Urinary Claudin-2, Caveolin-1, and EGF as Diagnostic Biomarkers of Necrotizing Enterocolitis in Preterm Neonates

Summary

Our study aims to determine the differences in the concentration of urinary claudin-2, caveolin-1, and epidermal growth factor (EGF) as non-invasive biomarkers in the diagnosis of Necrotizing Enterocolitis (NEC). We compare the concentration of urinary claudin-2, caveolin-1, and EGF between preterm neonates at risk of NEC and healthy term infants as the basis for determining NEC biomarkers with the most optimum sensitivity and specificity. This analytical observational study is based on biomolecular profiling with a prospective cohort design approach. The research subjects are a group of preterm neonates (gestational age of 28-34 weeks) who were admitted in Perinatology Unit, Department of Pediatrics, Saiful Anwar General Hospital, Malang and whom diagnosed with NEC using Bell's criteria and serum TGF-β levels. Subjects are selected by consecutive sampling and single-blind analysis was performed in the Laboratory of Bioscience and Biomedicine, Faculty of Medicine, University of Brawijaya.

During the research process, groups of preterm and term neonates would be observed and their clinical development followed. The collection of biologic samples would be taking 10 cc of urine and 40 mg of feces on day-5 (D5) and 7 (D7). The consecutive manner of urinary sampling was regarded to assess whether there was a time-related protein expression in the course of the NEC process. Faecal samples would be assessed for microbiota profile analysis described by the ratio of Proteobacteria: Firmicutes and Bacteroidetes to represent dysbiosis process in NEC. After 7 days, the subjects would be grouped into a group of preterm neonates with NEC, a group of healthy term neonates as a control, while a group of preterm infants at whom during the course of the study did not develop NEC, would be assigned to group of premature neonates without NEC.

Urinary protein concentrations from the three groups would then be analyzed and adjusted with normalized creatinine, so that the levels of these three proteins could be assessed quantitatively using the ELISA (Enzyme-Linked Immunosorbent Assay) method. The results would be compared with the microbiota profile as the golden standard for NEC cases. Through statistical tests, sensitivity, specificity and cut-off of selected protein levels would be assessed as diagnostic biomarkers of NEC.

Conditions

• Enterocolitis, Necrotizing
• Infant, Premature

Interventions

DIAGNOSTIC_TEST

Urinary Claudin-2

A sequential non-invasive urinary molecular profiling for protein, i.e. Claudin-2 as potential marker for enterocyte tight junction disruption, would be analyzed quantitatively with ELISA and then compared between groups to assess the optimum sensitivity and specificity.

DIAGNOSTIC_TEST

Urinary Caveolin-1

A sequential non-invasive urinary molecular profiling for protein, i.e. Caveolin-1 as potential marker for enterocyte tight junction disruption, would be analyzed quantitatively with ELISA and then compared between groups to assess the optimum sensitivity and specificity.

DIAGNOSTIC_TEST

Urinary EGF

A sequential non-invasive urinary molecular profiling for protein, i.e. epidermal growth factor (EGF) as potential marker for tight junction protective regulator, would be analyzed quantitatively with ELISA and then compared between groups to assess the optimum sensitivity.

Sponsors & Collaborators

• University of Brawijaya

  lead OTHER

Principal Investigators

• Brigitta IRV Corebime, M.D.(Paed) · Saiful Anwar General Hospital

Eligibility

Min Age

1 Day

Max Age

28 Days

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-03-17

Primary Completion

2022-05-31

Completion

2022-07-31

Countries

• Indonesia

Study Locations