Antenatal absent or reversed end-diastolic flow (AREDF) velocity through the umbilical arteries places preterm infants at significant risk for developing gastrointestinal complications, such as feeding intolerance, necrotizing enterocolitis or spontaneous intestinal perforation. Due to the fear of the aforementioned conditions, the establishment of adequate enteral feeds is frequently hampered in this population. Previous postnatal Doppler studies have shown that AREDF preterm infants who later developed feeding intolerance have a decreased blood flow velocity in the superior mesenteric artery in response to the first enteral feed; to date, however, it is not known whether this hemodynamic impairment persists over time, or if it is associated with reduced splanchnic oxygenation and perfusion, monitored by Near-infrared spectroscopy (NIRS).

This observational prospective study aims:

• to assess the patterns of abdominal oxygenation and perfusion in response to enteral feeds in AREDF preterm infants at different phases of enteral feeding establishment;
• to evaluate a possible correlation with the development of gastrointestinal complications.

Intrauterine growth restriction (IUGR) is a major cause of perinatal morbidity and mortality. Severe IUGR is often due to impaired placental circulation, with absent or reversed end-diastolic flow (AREDF) velocity through the umbilical arteries. Fetuses with AREDF adapt to chronic hypoxia by undergoing a blood flow redistribution, which favors cerebral perfusion at the expense of the mesenteric district. The resulting hypoxic-ischemic injury of the intestinal mucosa represents a major risk factor for the post-natal development of gastrointestinal complications, such as necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP) and feeding intolerance (FI). Due to the fear of the aforementioned conditions, the establishment of adequate enteral feeding in AREDF preterm infants is often difficult; hence, the identification of infants at highest risk for GI complications could aid their delicate nutritional management.

Postnatal Doppler studies have shown a decreased blood flow velocity in the superior mesenteric artery in response to the first enteral feed in AREDF preterm infants who later developed feeding intolerance. A similar Doppler impairment and lower values of splanchnic oxygenation at feeding introduction have been described in non-IUGR preterm infants with later GI complications. To date, however, it is not known whether the impaired mesenteric blood flow observed after the first feed in high-risk AREDF infants persists over time, or if it correlates with reduced splanchnic oxygenation and perfusion.

This observational prospective study aims:

• to assess the patterns of abdominal oxygenation and perfusion in response to enteral feeds in AREDF preterm infants at different phases of enteral feeding establishment;
• to evaluate a possible correlation with the development of gastrointestinal complications.

Infants admitted to the Neonatal Intensive Care Unit (NICU) are consecutively enrolled in the study if fulfilling the following criteria: gestational age ≤34 weeks, stable clinical conditions, documented evidence of antenatal umbilical Doppler impairment.

Exclusion criteria are:

• Enteral feeding prior to the enrollment
• Major congenital abnormalities (including congenital heart diseases, gastroschisis, exomphalos)
• Hemodynamic instability, hypotension, patent ductus arteriosus, anemia, sepsis or other infections at time of NIRS monitoring

Written, informed consent to participate in the study is obtained from the parents/legal guardians of each infant before enrollment.

Enrolled infants undergo a continuous monitoring of splanchnic oxygenation (SrSO2) at enteral feeding introduction (15 ml/kg/die volumes administered within the first 48 hours of life) and full enteral feeding (FEF) achievement (enteral intake ≥150 ml/kg/die) from 30' before to 3 h after feed administration by means of INVOS 5100 oximeter (Somanetics Corporation, Troy, MI, USA).

A simultaneous monitoring of peripheral oxygen saturation (SpO2) is be performed in order to calculate splanchnic fractional oxygen extraction (SFOE) ratio ([SpO2-SrSO2]/SpO2). SrSO2 values recorded during hypoxic episodes (SpO2 <85%) are excluded from statistical analysis.

GI complications are defined as NEC stage ≥2, SIP and/or FI (enteral feeding withholding ≥1 day because of suggestive clinical signs). Enrolled infants are retrospectively divided into two groups: lack (group 1) vs. development (group 2) of GI complications.

Data are analyzed using IBM SPSS Statistic version 20.0.0 (IBM Corporation, IBM Corporation Armonk, New York, United States). Clinical characteristics in the study groups are compared by Mann-Whitney U test for continuous variables and chi-square test for categorical variables. Mann-Whitney U test is used to compare abdominal SrSO2 and FSOE patterns in response to feeds between groups 1 and 2.

Inclusion Criteria:

• gestational age ≤34 weeks
• stable clinical conditions
• documented evidence of antenatal umbilical Doppler impairment
• written informed consent obtained from parents/guardians

Exclusion Criteria:

• Enteral feeding prior to the enrollment
• Major congenital abnormalities (including congenital heart diseases, gastroschisis, exomphalos)
• Hemodynamic instability, hypotension, patent ductus arteriosus, anemia, sepsis or other infections at time of NIRS monitoring

20 preterm infants admitted to the Neonatal Intensive Care Unit of Sant'Orsola-Malpighi University Hospital and fulfilling the inclusion criteria are going to be enrolled.