Prediction of NEC With Urinary iFABP

An Assessment of Urinary Intestinal Fatty Acid Binding Protein as a Early Predictor of Necrotizing Enterocolitis

During the first four days of life, intestinal fatty acid binding protein (iFABP) is elevated in the urine of premature babies who go on to develop necrotizing enterocolitis (NEC) days to weeks later. This study aims to determine whether the withholding of feedings in babies with an elevated urinary iFABP can reduce the incidence of NEC.

Study Overview

• Status: Withdrawn
• Conditions: Necrotizing Enterocolitis; Prematurity
• Intervention / Treatment: Other: Assessment of urinary iFABP; Other: Administration of enteral feedings

Detailed Description

Necrotizing enterocolits (NEC) occurs with an incidence of 3-7% in very low birth weight (<1500g) infants and is associated with significant morbidity and mortality. Earlier detection of a subclinical prodrome in NEC might allow for the institution of measures that could prevent or attenuate the severity of disease. We have demonstrated that levels of urinary intestinal fatty acid binding protein (iFABPu), a sensitive and specific marker for intestinal mucosal injury, were elevated in the first 4 days of life in all infants who subsequently developed NEC. We hypothesize that, in the context of an elevated iFABPu in the neonatal period, a significant proportion of NEC cases could be averted by not initiating feedings.

The proposed study will be a three-year prospective trial of iFABPu monitoring during the neonatal period in 220 infants of gestational age less than 33 weeks. Urine will be collected in 12-hour aliquots over the first four days of life and the iFABPu will be measured. On the afternoon of day of life four, infants in whom iFABPu exceeded 1000 pg/ml at any time will be continued with no feedings, iFABPu will continue to be measured, and trophic, breast milk feedings will only be initiated after iFABPu has normalized for five days. Infants with non-elevated iFABPu over the first four days of life will have feedings initiated on day of life four, in the absence of other contraindications. All subjects will have urine collected daily over their entire hospital stay for iFABPu assay. However, after the active study period (after feedings have been initiated) iFABPu findings will not be communicated to the physicians caring for the subjects, but will be evaluated retrospectively in order to better define the utility of iFABPu as a marker for impending NEC later in newborn life.

If iFABPu monitoring is shown to be effective in reducing the incidence of NEC it would revolutionize the care of premature infants by providing physicians with a tool that would permit feeding decisions to be based directly upon the viability of the intestine, rather than intuition.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gestational age less than 33 weeks
• Admission to Loma Linda University Children's Hospital NICU within 48 hours of life

Exclusion Criteria:

• Anuria
• Congenital gastrointestinal anomaly

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iFABP Monitored; Subjects monitored for urinary iFABP content during the first 4-12 days of life. Enteral feedings administered when iFABP levels are normal during the first four days of life or, if elevated during the first four days of life, have normalized for five days.	Other: Assessment of urinary iFABP; Other: Administration of enteral feedings

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of necrotizing enterocolitis	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to caloric goal for enteral feedings	90 days

Collaborators and Investigators

• Sponsor: Loma Linda University
• Investigators: Principal Investigator: Gerald Gollin, MD, Loma Linda University School of Medicine

Publications and helpful links

General Publications

• Mannoia K, Boskovic DS, Slater L, Plank MS, Angeles DM, Gollin G. Necrotizing enterocolitis is associated with neonatal intestinal injury. J Pediatr Surg. 2011 Jan;46(1):81-5. doi: 10.1016/j.jpedsurg.2010.09.069.
• Stadie D, Boskovic DS, Plank MS, et al. Elevated urinary intestinal fatty acid binding protein precedes clinical indicators of necrotizing enterocolitis. JSR 179:319, 2013.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): July 1, 2016
• Study Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: March 4, 2013
• First Submitted That Met QC Criteria: March 5, 2013
• First Posted (Estimate): March 6, 2013

Study Record Updates

• Last Update Posted (Estimate): May 14, 2015
• Last Update Submitted That Met QC Criteria: May 13, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Biomarkers; Prematurity; Necrotizing Enterocolitis; Feeding; Intestinal Fatty Acid Binding Protein
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: 215610