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Placental InsufficiencyAREDF-SONCT02971566

Splanchnic Oxygenation Response to Enteral Feeds in Preterm Infants With Abnormal Antenatal Doppler.

An observational study of Placental Insufficiency and NEC - Necrotizing Enterocolitis, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 day to 2 months
How many people
20 participants
Where
1 siteItaly
Study dates
Feb 2013to Oct 2016
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 day to 2 months
  • All sexes
  • No healthy volunteers
  • Child

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.

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • Neonatal Intensive Care Unit of the S.Orsola-Malpighi Hospital

    Bologna, Italy, 40138

Other trials in Italy

About this study

Official title: Splanchnic Oxygenation and Perfusion Response to Enteral Feeds in Preterm Infants With Abnormal Antenatal Doppler: Pattern Assessment and Correlation With Feeding Intolerance

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.
Read the 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.

Keywords
feeding intolerance, preterm infants, near infrared spectroscopy, abnormal antenatal Doppler
Medical subject headings
Placental Insufficiency, Enterocolitis, Necrotizing, Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02971566
Study groupRoleWhat they receive
Gastrointestinal complicationsDevelopment of one ore more of the following gastrointestinal complications: * necrotizing enterocolitis (stage ≥2) * spontaneous intestinal perforation * feeding intolerance, defined as enteral feeding withholding ≥1 day because of suggestive clinical signs
Controlsno evidence of gastrointestinal complications during the hospitalization

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Increase/reduction of SrSO2 after enteral feeds

    Increase/reduction of SrSO2 values in response to enteral feeds in infants who have developed gastrointestinal complications during their hospitalization.

    Measured: 3.5 hours

Secondary outcomes (1)
  1. Increase/reduction of FSOE after enteral feeds

    Increase/reduction of SrSO2 values in response to enteral feeds in infants who have developed gastrointestinal complications during their hospitalization.

    Measured: 3.5 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2016 (estimated)
  2. Study startFeb 2013
  3. Primary completionOct 2016
  4. Study completionOct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02971566
Sponsor's protocol ID
SO-2016-AREDF
Acronym
AREDF-SO
Status last verified
Nov 2016
First submitted
19 Nov 2016
Last updated
23 Nov 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Kempley S, Gupta N, Linsell L, Dorling J, McCormick K, Mannix P, Juszczak E, Brocklehurst P, Leaf A; ADEPT Trial Collaborative Group. Feeding infants below 29 weeks' gestation with abnormal antenatal Doppler: analysis from a randomised trial. Arch Dis Child Fetal Neonatal Ed. 2014 Jan;99(1):F6-F11. doi: 10.1136/archdischild-2013-304393. Epub 2013 Aug 23.

    PubMed 23973795
  • Bora R, Mukhopadhyay K, Saxena AK, Jain V, Narang A. Prediction of feed intolerance and necrotizing enterocolitis in neonates with absent end diastolic flow in umbilical artery and the correlation of feed intolerance with postnatal superior mesenteric artery flow. J Matern Fetal Neonatal Med. 2009 Nov;22(11):1092-6. doi: 10.3109/14767050903029600.

    PubMed 19900051
  • Kempley ST, Gamsu HR, Vyas S, Nicolaides K. Effects of intrauterine growth retardation on postnatal visceral and cerebral blood flow velocity. Arch Dis Child. 1991 Oct;66(10 Spec No):1115-8. doi: 10.1136/adc.66.10_spec_no.1115.

    PubMed 1750758
  • Martini S, Aceti A, Beghetti I, Faldella G, Corvaglia L. Feed-related Splanchnic Oxygenation in Preterm Infants With Abnormal Antenatal Doppler Developing Gut Complications. J Pediatr Gastroenterol Nutr. 2018 May;66(5):755-759. doi: 10.1097/MPG.0000000000001804.

    PubMed 29112084

Questions about this trial

What is this clinical trial studying?

An observational study of Placental Insufficiency and NEC - Necrotizing Enterocolitis, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Increase/reduction of SrSO2 after enteral feeds (time frame: 3.5 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02971566, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2016.

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