Intestinal Perfusion After Feeding in Preterm and Term Infants

This is a pilot exploratory observational prospective cohort phase I study. In this study, we will gather preliminary data to evaluate (i) the magnitude of changes in blood flow in the bowel before and after feeding and (ii) the differences between preterm and term infants.

Study Overview

• Status: Not yet recruiting
• Conditions: Necrotizing Enterocolitis; Premature
• Intervention / Treatment: Other: Evaluation of intestinal perfusion with color Doppler abdominal ultrasound before and after feeding.

Detailed Description

Necrotizing enterocolitis (NEC) is the most devastating intestinal disease which remains a major unsolved clinical challenge in neonatology. NEC is predominantly a disease of preterm or extremely preterm infants. NEC results in high mortality, neurodevelopmental impairment, intestinal failure, and reduced quality of life.

Prematurity and enteral feeding are two of the most important risk factors for NEC. More than 90% of infants with NEC have been enterally fed, suggesting that feeding is an important priming step in making the intestine vulnerable to NEC. Absorption of nutrients is energy-consuming and results in an increased oxygen demand after feeding, followed by an increase in intestinal blood flow above baseline (known as postprandial hyperemia). Our preclinical studies have shown an intriguing discovery, that prematurity is associated with a remarkably reduced intestinal response to feeding, which predisposes the intestine to NEC.

However, there is lack of reliable clinical evidence to compare the magnitude of difference in postprandial intestinal blood flow in human preterm versus term infants. If preterm infants do in fact demonstrate a diminished intestinal blood flow response to feeding, this will shed light on the need for interventions in the feeding protocol of this vulnerable population to prevent the development of NEC.

This study is a phase I exploratory prospective cohort study. We will gather preliminary data to evaluate (i) the magnitude of changes in blood flow in the bowel before and after feeding and (ii) the differences between preterm and term infants.

In a cohort of 20 patients (10 preterm, 10 term), we will evaluate feeding-related perfusion of the superior mesenteric artery and bowel wall immediately before and 60-minutes after feeding.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Agostino Pierro, OBE, MD, FRCS, FAAP; Phone Number: 309350 4168137654; Email: agostino.pierro@sickkids.ca
• Study Contact Backup: Name: Niloofar Ganji, BSc, MSc; Phone Number: 6478702781; Email: niloofar.ganji@sickkids.ca

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Children's Hospital of Fudan University (Xiamen Branch)
      • Contact: Haitao Zhu, MD; Phone Number: +86-592-2529586; Email: haitao_zhu@fudan.edu.cn
      • Principal Investigator: Haitao Zhu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of 2 cohorts:

• Preterm infants (≤33 weeks gestational age at birth) of any birth weight receiving full bolus enteral feeding.
• Term infants of any birth weight aged 1-4 weeks.

The sources of preterm infants are level III/IV neonatal intensive care units at Xiamen Children's Hospital and the Hospital for Sick Children. The source of the cohort of term infants will be Level II neonatal ward at Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital and the Hospital for Sick Children.

Description

Inclusion Criteria:

• Preterm infants (≤33 weeks gestational age) of any birth weight receiving full bolus enteral feeding.

Exclusion Criteria:

• Neonates receiving bolus enteral feeds lasting >30 minutes or continuous enteral feeds will be excluded to avoid overlapping or close timing between pre- and post-prandial intestinal perfusion measurements.
• Large patent ductus arteriosus (PDA)
• Major congenital malformations
• Suspected genetic syndrome
• Ssuspected or confirmed infection
• Fraction of inspired oxygen of ≥0.60 at enrollment
• Confirmed diagnosis of necrotizing enterocolitis diagnosis. NEC will be diagnosed when at least two of the following clinical signs and one radiological sign will be present: (i) Clinical signs (1. abdominal distension; 2. abdominal tenderness; 3. abdominal discoloration; 4. blood in stool). (ii) Radiological signs (1. Pneumoperitoneum; 2. pneumatosis; 3. portal venous gas).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Preterm infants; Preterm infants (≤33 weeks gestational age) of any birth weight receiving full bolus enteral feeding, aged 1-4 weeks.	Other: Evaluation of intestinal perfusion with color Doppler abdominal ultrasound before and after feeding.; This is an observation study involving measurement of intestinal perfusion with color Doppler abdominal ultrasound before and after feeding. No intervention is given to study participants.; Other Names: No intervention.
Term infants; Term infants of any birth weight aged 1-4 weeks.	Other: Evaluation of intestinal perfusion with color Doppler abdominal ultrasound before and after feeding.; This is an observation study involving measurement of intestinal perfusion with color Doppler abdominal ultrasound before and after feeding. No intervention is given to study participants.; Other Names: No intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-averaged mean velocity of the superior mesenteric artery	Abdominal ultrasound is used to measure the percent change in time-averaged mean velocity (TAMV) of the superior mesenteric artery (SMA) between pre and post-prandial assessments.	Measured immediately before and 60 minutes after feeding

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bowel wall perfusion	Color Doppler abdominal ultrasound is used to measure changes in peripheral perfusion of the bowel wall pre- and post-prandially.	Measured immediately before and 60 minutes after feeding

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Xiamen Children's Hospital

Publications and helpful links

General Publications

• Chen Y, Koike Y, Chi L, Ahmed A, Miyake H, Li B, Lee C, Delgado-Olguin P, Pierro A. Formula feeding and immature gut microcirculation promote intestinal hypoxia, leading to necrotizing enterocolitis. Dis Model Mech. 2019 Dec 9;12(12):dmm040998. doi: 10.1242/dmm.040998.
• Chen Y, Koike Y, Miyake H, Li B, Lee C, Hock A, Zani A, Pierro A. Formula feeding and systemic hypoxia synergistically induce intestinal hypoxia in experimental necrotizing enterocolitis. Pediatr Surg Int. 2016 Dec;32(12):1115-1119. doi: 10.1007/s00383-016-3997-8. Epub 2016 Nov 4.

Study record dates

Study Major Dates

• Study Start (Estimated): April 2, 2024
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: March 18, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: intestinal perfusion; postprandial intestinal perfusion; Color Doppler abdominal ultrasound
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: Postfeed Intestinal Perfusion

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No