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.

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.

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).

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.