Splanchnic Oxygenation Response to Enteral Feeds in Preterm Infants With Abnormal Antenatal Doppler.
Condition: Placental Insufficiency; NEC - Necrotizing Enterocolitis; Newborn, Premature; Feeding Disorder Neonatal
MeSH terms: Enterocolitis; Enterocolitis, Necrotizing; Placental Insufficiency; Feeding and Eating Disorders
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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.
      
Keywords: feeding intolerance; preterm infants; near infrared spectroscopy; abnormal antenatal Doppler