Intrauterine Growth RestrictionPTI'DOPNCT03865628
Ultrasound Evaluation of Fetal Hemodynamics and Perinatal Complications
An observational study of Intrauterine Growth Restriction and Small-for-gestational Age, run by Centre Hospitalier Universitaire de Besancon.
Trial summary
In case of fetal weight below the 10th centile for gestational age, it is important to distinguish SGA and IUGR. SGA is defined as a fetal weight below the 10th centile. IUGR correspond to a pathologic reduction of growth velocity and it is a major determinant of perinatal mortality and morbidity. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Intrauterine Growth Restriction, Small-for-gestational Age
- How many people
- 1,200 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2019to 31 Dec 2020
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Study population: Study population correspond to the patients follow up in one of the materno-fetal medicine unit, multidisciplinary reference unit for the diagnosis, the investigation and management of materno-fetal diseases.
Who may be able to join
- Singleton pregnancy
- Estimation of the fetal weight less than estimation the 10th percentile
Who cannot join
- Refusal of parents
- Fetal and vascular malformations
- Fetal anemia
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Ultrasound Evaluation of Fetal Hemodynamics and Its Variations in Small Fetuses Looking for Prognostic Factors of Perinatal Complications
In case of fetal weight below the 10th centile for gestational age, it is important to distinguish SGA and IUGR. SGA is defined as a fetal weight below the 10th centile. IUGR correspond to a pathologic reduction of growth velocity and it is a major determinant of perinatal mortality and morbidity. Even if SGA have long time been considered to be constitutionally small without adverse outcomes, recent evidence has demonstrated that a proportion of SGA, with normal UA Doppler, could be associated with neonatal adverse outcomes, probably related to a late-onset IUGR. Therefore, it seems essential to differentiate several categories of fetuses presenting abnormal fetal weight or intrauterine growth: fetuses SGA without any Doppler abnormalities, fetuses affected by early or late-IUGR. In case of late-IUGR, an important part of these fetuses is initially considered as PAG with a normal umbilical Doppler.
In case of fetal weight below the 10th centile for gestational age, longitudinal assessment of the fetal weight and umbilical artery (UA) Doppler is recommended. In case of abnormal UA Doppler, Middle Cerebral Artery (MCA) Doppler is recommended to research a "brain-sparing" effect. If UA and MCA Doppler findings seem to become abnormal in the early stages of IUGR, Ductus Venosus (DV) flow abnormalities have been described as a late marker of fetal decompensation related to an acute myocardial impaired relaxation and acidemia which is a major contributor to adverse perinatal outcome and neurological. The aortic isthmus (AoI) Doppler is an indicator of the progression of fetal hemodynamic deterioration in IUGR and recent data confirm that AoI and DV abnormalities are correlated but AoI Doppler abnormalities would occur earlier than DV Doppler. AoI Doppler could identify abnormalities suggestive of right ventricular dysfunction before DV Doppler and anticipate obstetrical management. In conclusion, Doppler examination could not be reduced to UA Doppler in case of SGA and IUGR and require a global examination including MCA and probably DV and AoI Doppler.
That's why fetal growth assessment should not be limited to fetal biometry and umbilical artery Doppler. Thanks to a systematic protocol for Doppler examination based on UA, MCA, DV and Aortic Isthmus (AoI) Doppler, we hope identify these hemodynamic variations in a large cohort of fetuses <10 to improve prenatal assessment of these foetus to and perinatal outcomes, reducing perinatal morbi-mortality.
Read the detailed description
All women were followed at one referent matron-fetal medicine unit where they delivered or to which they were referred for abnormalities of the fetal growth. Conforming to national guidelines, referent ultrasound scans and longitudinal assessment of the estimated fetal weight (EFW) were performed depending on the EFW. Each eligible woman was given an information sheet concerning the study protocol.
Fetal biometry and Doppler were performed thanks to a standardised protocol based on international guidelines. In all instances, ultrasound examinations were performed by one experienced and certified operators using an ultrasound machine (GE Voluson E8/E10, GE Medical Systems). EFW was calculated from head and abdominal circumferences and femur length using the formula of Hadlock. The reference growth curves was CFEF growth curves.
Pulsed Doppler measurements were performed automatically, based on at least three consecutive waveforms, with angle of insonation as close to 0° as possible and always below 30°. A high-pass filter of 70 Hz was used to record low-flow velocities and to avoid artifacts. The Umbilical Artery (UA)-PI Doppler were measured at the placental insertion of the funicular cord. The Middle Cerebral Artery (MCA)-PI was obtained in a transverse view of the fetal head, at the level of its origin from the circle of Willis, and the cerebroplacental ratio (CPR) was calculated as the ratio MCA-PI / UA-PI. Aortic Isthmus (AoI)-PI was measured at the level of the three vessels and trachea view, placing the gate just before the convergence of the AoI and the arterial duct. Ductus Venosus (DV)-PI was measured in a mid-sagittal or transverse section of the fetal abdomen, positioning the Doppler gate at its isthmic portion. Participation in the study does not lead to any change in practices or additional data.
In order to ensure the reproducibility of the data and to limit the measurement biases, we will perform a second reading of the Doppler to verify the application of the measurement protocol, especially: acquisition, Doppler spectrum and measurements. A first analysis will focus on the first 10 patients included per center and then, a random analysis on 10 patients every 100 patients included.
Regularly, data monitoring will be made by a scientific technician to reduce missing data.
Anonymous sonographic data were automatically extracted from the electronic patient record (Diamm (MICRO6 SARL) or ViewPoint (General Electric Healthcare France)) and compiled into an electronic case report form with demographic, maternal, obstetrical and neonatal data. Regular extraction will allow to test extraction pipeline and statistical test.
Given a 10% prevalence of SGA, an expected inclusion rate with completed data of 90% and the number of births in the several units, a sample size of 1200 newborns was sufficient to identify 20% of adverse perinatal outcome.
Quantitative variables will be described using the following parameters: mean, standard deviation, median, and minimum and maximum values. Qualitative variables will be described by the frequency and proportion of each class. The qualitative variables will be compared by Chi² test or Fisher exact test. Quantitative variables will be compared by a Student test or a Mann \& Whitney test. We will focus on describing the temporal dynamics of the cerebro-aortic relationship.
- Keywords
- Doppler, Ombilical artery, Middel cerebral artery, Ductus venous, Aortic isthmus, Amniotic fluid, Intrauterine Growth Restriction, Small-for-gestational Age, Prognosis
- Medical subject headings
- Fetal Growth Retardation
What is being measured
The primary outcome is the main question the study is designed to answer.
Global perinatal morbidity and mortality
Defined by the occurrence of at least one of the following events (composite outcome of the french national epidemiological study "EPIPAGE"):
- perinatal death
- stage 3 or 4 intraventricular haemorrhage
- cystic periventricular leukomalacia
- hyperoxic retinopathy treated using laser
- ulcerative necrotizing enterocolitis
- bronchopulmonary dysplasia
Measured: 1 month after birth
Secondary outcomes (2)
Specific perinatal morbidity and mortality
Defined by the occurrence of at each events belonging of the composite primary outcome.
Measured: 1 month after birth
Early neonatal morbidity
Defined by the occurrence of at least one of the following events (composite TASK FORCE outcome) :
- fetal metabolic acidosis with pH <7.00 and base excess> 12 mmol / L
- early onset of severe or moderate neonatal encephalopathy (after 34 weeks of gestational age)
- cerebral palsy
- absence of other causes of encephalopathies (traumatic, bleeding disorders, infections, genetics)
Measured: 1 week after birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start1 Mar 2019 (estimated)
- Primary completion31 Aug 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Intrauterine Growth RestrictionStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Hospitalier Universitaire Dijon, University Hospital, Strasbourg, France, Centre Hospitalier Auxerre, Hopital Nord Franche-Comte
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03865628
- Sponsor's protocol ID
- API/2017/89
- Acronym
- PTI'DOP
- Status last verified
- Feb 2019
- First submitted
- 4 Mar 2019
- Last updated
- 7 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Meher S, Hernandez-Andrade E, Basheer SN, Lees C. Impact of cerebral redistribution on neurodevelopmental outcome in small-for-gestational-age or growth-restricted babies: a systematic review. Ultrasound Obstet Gynecol. 2015 Oct;46(4):398-404. doi: 10.1002/uog.14818.
PubMed 25683973Benavides-Serralde A, Scheier M, Cruz-Martinez R, Crispi F, Figueras F, Gratacos E, Hernandez-Andrade E. Changes in central and peripheral circulation in intrauterine growth-restricted fetuses at different stages of umbilical artery flow deterioration: new fetal cardiac and brain parameters. Gynecol Obstet Invest. 2011;71(4):274-80. doi: 10.1159/000323548. Epub 2011 Feb 24.
PubMed 21346314Figueras F, Benavides A, Del Rio M, Crispi F, Eixarch E, Martinez JM, Hernandez-Andrade E, Gratacos E. Monitoring of fetuses with intrauterine growth restriction: longitudinal changes in ductus venosus and aortic isthmus flow. Ultrasound Obstet Gynecol. 2009 Jan;33(1):39-43. doi: 10.1002/uog.6278.
PubMed 19115231Cruz-Martinez R, Figueras F, Hernandez-Andrade E, Oros D, Gratacos E. Changes in myocardial performance index and aortic isthmus and ductus venosus Doppler in term, small-for-gestational age fetuses with normal umbilical artery pulsatility index. Ultrasound Obstet Gynecol. 2011 Oct;38(4):400-5. doi: 10.1002/uog.8976. Epub 2011 Jul 26.
PubMed 21567514Baschat AA. Planning management and delivery of the growth-restricted fetus. Best Pract Res Clin Obstet Gynaecol. 2018 May;49:53-65. doi: 10.1016/j.bpobgyn.2018.02.009. Epub 2018 Mar 1.
PubMed 29606482
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultrasound Evaluation of Fetal Hemodynamics and Its Variations in Small Fetuses Looking for Prognostic Factors of Perinatal Complications
- ClinicalTrials.gov ID
- NCT03865628
- Acronym / sponsor ID
- PTI'DOP / API/2017/89
- Keywords
- Doppler, Ombilical artery, Middel cerebral artery, Ductus venous, Aortic isthmus, Amniotic fluid, Intrauterine Growth Restriction, Small-for-gestational Age
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Collaborators
- Centre Hospitalier Universitaire Dijon, University Hospital, Strasbourg, France, Centre Hospitalier Auxerre, Hopital Nord Franche-Comte
- Study start
- 1 Mar 2019 (estimated)
- Primary completion
- 31 Aug 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 7 Mar 2019 (actual)
- 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.
In case of fetal weight below the 10th centile for gestational age, it is important to distinguish SGA and IUGR. SGA is defined as a fetal weight below the 10th centile. IUGR correspond to a pathologic reduction of growth velocity and it is a major determinant of perinatal mortality and morbidity. Even if SGA have long time been considered to be constitutionally small without adverse outcomes, recent evidence has demonstrated that a proportion of SGA, with normal UA Doppler, could be associated with neonatal adverse outcomes, probably related to a late-onset IUGR. Therefore, it seems essential to differentiate several categories of fetuses presenting abnormal fetal weight or intrauterine growth: fetuses SGA without any Doppler abnormalities, fetuses affected by early or late-IUGR. In case of late-IUGR, an important part of these fetuses is initially considered as PAG with a normal umbilical Doppler.
In case of fetal weight below the 10th centile for gestational age, longitudinal assessment of the fetal weight and umbilical artery (UA) Doppler is recommended. In case of abnormal UA Doppler, Middle Cerebral Artery (MCA) Doppler is recommended to research a "brain-sparing" effect. If UA and MCA Doppler findings seem to become abnormal in the early stages of IUGR, Ductus Venosus (DV) flow abnormalities have been described as a late marker of fetal decompensation related to an acute myocardial impaired relaxation and acidemia which is a major contributor to adverse perinatal outcome and neurological. The aortic isthmus (AoI) Doppler is an indicator of the progression of fetal hemodynamic deterioration in IUGR and recent data confirm that AoI and DV abnormalities are correlated but AoI Doppler abnormalities would occur earlier than DV Doppler. AoI Doppler could identify abnormalities suggestive of right ventricular dysfunction before DV Doppler and anticipate obstetrical management. In conclusion, Doppler examination could not be reduced to UA Doppler in case of SGA and IUGR and require a global examination including MCA and probably DV and AoI Doppler.
That's why fetal growth assessment should not be limited to fetal biometry and umbilical artery Doppler. Thanks to a systematic protocol for Doppler examination based on UA, MCA, DV and Aortic Isthmus (AoI) Doppler, we hope identify these hemodynamic variations in a large cohort of fetuses <10 to improve prenatal assessment of these foetus to and perinatal outcomes, reducing perinatal morbi-mortality.
Detailed description
All women were followed at one referent matron-fetal medicine unit where they delivered or to which they were referred for abnormalities of the fetal growth. Conforming to national guidelines, referent ultrasound scans and longitudinal assessment of the estimated fetal weight (EFW) were performed depending on the EFW. Each eligible woman was given an information sheet concerning the study protocol.
Fetal biometry and Doppler were performed thanks to a standardised protocol based on international guidelines. In all instances, ultrasound examinations were performed by one experienced and certified operators using an ultrasound machine (GE Voluson E8/E10, GE Medical Systems). EFW was calculated from head and abdominal circumferences and femur length using the formula of Hadlock. The reference growth curves was CFEF growth curves.
Pulsed Doppler measurements were performed automatically, based on at least three consecutive waveforms, with angle of insonation as close to 0° as possible and always below 30°. A high-pass filter of 70 Hz was used to record low-flow velocities and to avoid artifacts. The Umbilical Artery (UA)-PI Doppler were measured at the placental insertion of the funicular cord. The Middle Cerebral Artery (MCA)-PI was obtained in a transverse view of the fetal head, at the level of its origin from the circle of Willis, and the cerebroplacental ratio (CPR) was calculated as the ratio MCA-PI / UA-PI. Aortic Isthmus (AoI)-PI was measured at the level of the three vessels and trachea view, placing the gate just before the convergence of the AoI and the arterial duct. Ductus Venosus (DV)-PI was measured in a mid-sagittal or transverse section of the fetal abdomen, positioning the Doppler gate at its isthmic portion. Participation in the study does not lead to any change in practices or additional data.
In order to ensure the reproducibility of the data and to limit the measurement biases, we will perform a second reading of the Doppler to verify the application of the measurement protocol, especially: acquisition, Doppler spectrum and measurements. A first analysis will focus on the first 10 patients included per center and then, a random analysis on 10 patients every 100 patients included.
Regularly, data monitoring will be made by a scientific technician to reduce missing data.
Anonymous sonographic data were automatically extracted from the electronic patient record (Diamm (MICRO6 SARL) or ViewPoint (General Electric Healthcare France)) and compiled into an electronic case report form with demographic, maternal, obstetrical and neonatal data. Regular extraction will allow to test extraction pipeline and statistical test.
Given a 10% prevalence of SGA, an expected inclusion rate with completed data of 90% and the number of births in the several units, a sample size of 1200 newborns was sufficient to identify 20% of adverse perinatal outcome.
Quantitative variables will be described using the following parameters: mean, standard deviation, median, and minimum and maximum values. Qualitative variables will be described by the frequency and proportion of each class. The qualitative variables will be compared by Chi² test or Fisher exact test. Quantitative variables will be compared by a Student test or a Mann \& Whitney test. We will focus on describing the temporal dynamics of the cerebro-aortic relationship.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study population correspond to the patients follow up in one of the materno-fetal medicine unit, multidisciplinary reference unit for the diagnosis, the investigation and management of materno-fetal diseases.
Key inclusion criteria (2 listed)
- Singleton pregnancy
- Estimation of the fetal weight less than estimation the 10th percentile
Key exclusion criteria (3 listed)
- Refusal of parents
- Fetal and vascular malformations
- Fetal anemia
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
Global perinatal morbidity and mortality
Time frame: 1 month after birth
Defined by the occurrence of at least one of the following events (composite outcome of the french national epidemiological study "EPIPAGE"): * perinatal death * stage 3 or 4 intraventricular haemorrhage * cystic periventricular leukomalacia * hyperoxic retinopathy treated using laser * ulcerative necrotizing enterocolitis * bronchopulmonary dysplasia
2 secondary outcomes
Specific perinatal morbidity and mortality
Time frame: 1 month after birth
Early neonatal morbidity
Time frame: 1 week after birth
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2019.
- Background: PubMed 25683973Meher S, Hernandez-Andrade E, Basheer SN, Lees C. Impact of cerebral redistribution on neurodevelopmental outcome in small-for-gestational-age or growth-restricted babies: a systematic review. Ultrasound Obstet Gynecol. 2015 Oct;46(4):398-404. doi: 10.1002/uog.14818.
- Background: PubMed 21346314Benavides-Serralde A, Scheier M, Cruz-Martinez R, Crispi F, Figueras F, Gratacos E, Hernandez-Andrade E. Changes in central and peripheral circulation in intrauterine growth-restricted fetuses at different stages of umbilical artery flow deterioration: new fetal cardiac and brain parameters. Gynecol Obstet Invest. 2011;71(4):274-80. doi: 10.1159/000323548. Epub 2011 Feb 24.
- Background: PubMed 19115231Figueras F, Benavides A, Del Rio M, Crispi F, Eixarch E, Martinez JM, Hernandez-Andrade E, Gratacos E. Monitoring of fetuses with intrauterine growth restriction: longitudinal changes in ductus venosus and aortic isthmus flow. Ultrasound Obstet Gynecol. 2009 Jan;33(1):39-43. doi: 10.1002/uog.6278.
- Background: PubMed 21567514Cruz-Martinez R, Figueras F, Hernandez-Andrade E, Oros D, Gratacos E. Changes in myocardial performance index and aortic isthmus and ductus venosus Doppler in term, small-for-gestational age fetuses with normal umbilical artery pulsatility index. Ultrasound Obstet Gynecol. 2011 Oct;38(4):400-5. doi: 10.1002/uog.8976. Epub 2011 Jul 26.
- Background: PubMed 29606482Baschat AA. Planning management and delivery of the growth-restricted fetus. Best Pract Res Clin Obstet Gynaecol. 2018 May;49:53-65. doi: 10.1016/j.bpobgyn.2018.02.009. Epub 2018 Mar 1.
- 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.
Questions about this trial
What is this clinical trial studying?
An observational study of Intrauterine Growth Restriction and Small-for-gestational Age, run by Centre Hospitalier Universitaire de Besancon.
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 2 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: status not confirmed, as of the sponsor's last update on 7 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nicolas MOTTET, MD (03 81 21 88 95, ncmottet@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global perinatal morbidity and mortality (time frame: 1 month after birth). 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 NCT03865628, which also lists 5 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 7 Mar 2019.