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.
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
- Conditions the study is for
- Placental Insufficiency, NEC - Necrotizing Enterocolitis, Newborn, Premature
- 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
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.
- Conditions
- Placental Insufficiency, NEC - Necrotizing Enterocolitis, Newborn, Premature, Feeding Disorder Neonatal
- 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 group | Role | What they receive |
|---|---|---|
| Gastrointestinal complications | Development 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 | |
| Controls | no evidence of gastrointestinal complications during the hospitalization |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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.
- First posted23 Nov 2016 (estimated)
- Study startFeb 2013
- Primary completionOct 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Placental InsufficiencyStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luigi Corvaglia, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Investigators
- Luigi T Corvaglia, Prof, Principal investigator, IRCCS Azienda Ospedaliero-Universitaria di Bologna
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 23973795Bora 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 19900051Kempley 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 1750758Martini 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
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Splanchnic Oxygenation and Perfusion Response to Enteral Feeds in Preterm Infants With Abnormal Antenatal Doppler: Pattern Assessment and Correlation With Feeding Intolerance
- ClinicalTrials.gov ID
- NCT02971566
- Acronym / sponsor ID
- AREDF-SO / SO-2016-AREDF
- Conditions
- Placental Insufficiency, NEC - Necrotizing Enterocolitis, Newborn, Premature, Feeding Disorder Neonatal
- Keywords
- feeding intolerance, preterm infants, near infrared spectroscopy, abnormal antenatal Doppler
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 23 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gastrointestinal complications | – | –Development 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 |
| Controls | – | –no evidence of gastrointestinal complications during the hospitalization |
Who may qualify
- Ages
- 1 day to 2 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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.
Key inclusion criteria (4 listed)
- gestational age ≤34 weeks
- stable clinical conditions
- documented evidence of antenatal umbilical Doppler impairment
- written informed consent obtained from parents/guardians
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Increase/reduction of SrSO2 after enteral feeds
Time frame: 3.5 hours
Increase/reduction of SrSO2 values in response to enteral feeds in infants who have developed gastrointestinal complications during their hospitalization.
1 secondary outcome
Increase/reduction of FSOE after enteral feeds
Time frame: 3.5 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2016.
- Background: PubMed 23973795Kempley 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.
- Background: PubMed 19900051Bora 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.
- Background: PubMed 1750758Kempley 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.
- Derived from this study: PubMed 29112084Martini 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luigi T Corvaglia, Prof principal investigator
IRCCS Azienda Ospedaliero-Universitaria di Bologna
1 site in 1 country: see every site and its status.
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.