IUGRCADETTENCT02583763
Cardiac Displacement From Third Trimester to Early Childhood
An observational study of IUGR and Fetal Growth Retardation, run by University Hospital, Linkoeping at 2 sites in Sweden.
Trial summary
The aim is to increase awareness of the relationship between (IUGR) and cardiac function in the foetus, the development of cardiac function over time after delivery and what significance a possible early disturbed myocardial function have for the neonate and the child during the first years of life. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- IUGR, Fetal Growth Retardation, Intrauterine Growth Restriction
- What is being tested?
- Echocardiography and Blood sample
- Type of treatment
- Surgery or procedure
- How many people
- 61 participants
- Where
- 2 sitesSweden
- Study dates
- Jan 2013to Dec 2027
- How long will I take part?
- 9 Years
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: This is a prospective case-control study in which fetuses from normal pregnancies will be compared with fetuses with IUGR. Parents will be asked to participate in the study in connection with the routine ultrasound examinations at the department of obstetrics to where they have been referred because of suspected IUGR. The control group will be randomly selected among pregnant women who come for routine ultrasound during pregnancy at gestational week 18-20.
Who may be able to join
- Inclusion of research subjects: Growth restriction in routine pregnancy ultrasound, verified by specialist control. Gestational age based on Crown Rump Length measurements during the first trimester. Growth restriction defined by a deviation more than 22% from the normal curve at a given gestational age or growth rate deviates more than 10% compared to the previous measurement in relation to the expected weight.
- Inclusion of controls: Control individuals recruited among mothers who come to routine pregnancy ultrasound control at gestational week 18. These are randomly selected and then asked to participate.
Who cannot join
- Exclusion of both the cases with IUGR and the control cases are major malformations, twin pregnancy, signs of intrauterine infection during pregnancy, significant illness or significant medical treatment of the mother.
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Dept of Obstetrics and Gynecology
Linköping, 58185
Paediatric Department University Hospital
Linköping, 59071
About this study
The aim is to increase awareness of the relationship between (IUGR) and cardiac function in the foetus, the development of cardiac function over time after delivery and what significance a possible early disturbed myocardial function have for the neonate and the child during the first years of life.
Read the detailed description
This is a prospective case-control study in which fetuses from normal pregnancies will be compared with fetuses with IUGR. Parents will be asked to participate in the study in connection with the routine ultrasound examinations at the department of obstetrics to where they have been referred because of suspected IUGR. The control group will be randomly selected among pregnant women who come for routine ultrasound during pregnancy at gestational week 18-20.
Surveys will be performed in the third trimester and after delivery. During the ultrasound examinations standardized, moving sequences of the heart will be saved. Analyses will be performed off-line and analysed by vector velocity imaging software. With this technique, the investigator can quantify the chamber wall and myocardial movements. Speed (velocity), movement (displacement) and thickening/deformation (strain and strain rate) will be recorded in a structured and standardized manner.
When performing the analysis the heart's walls are outlined and the software extracts the movement in different directions.
Data will be obtained concerning the participating mothers previous illness, mothers' age, maternal smoking, BMI, any abnormalities during pregnancy, number of previous pregnancies. Other data that will be recorded are means of delivery and any abnormalities during previous pregnancies, such as hypertension, preeclampsia and pre-natal steroid treatment.
Additional data to be collected from the participating fetuses are flow profiles in the umbilical artery, ductus venosus and middle cerebral artery. Abdominal circumference and estimated weight will be registered.
Following delivery, the participating child's height, weight, head circumference and gestational age at birth are registered. Additional data that will be collected after delivery are umbilical vein and umbilical artery acid base values, Apgar score. If admitted to the pediatric ward the investigators will register the number of days hospitalized in the ward for post-natal care and diagnosis. The investigators plan to examine the participating baby with cardiac ultrasound between 12 and 72 hours after delivery and again when the participating child is 3-4 months old and at 7-9 years of age.
The investigators will take a blood sample from the umbilical cord at birth and again at 7-9 years of age. The investigators will analyse the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the participating children's DNA.
Based on power calculation the investigators plan to examine between 20-30 fetuses with IUGR and 40-60 healthy fetuses in the control group.
- Being tested
- Echocardiography, Blood sample
- Keywords
- pro-brain natriuretic peptide (1-76), Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Echocardiography, Velocity Vector Imaging, Heart Function Tests
- Medical subject headings
- Fetal Growth Retardation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EchocardiographyOther
During the ultrasound examinations standardized, moving sequences of the heart will be saved. Analyzes are performed off-line and analyzed by vector velocity imaging software.
Blood sampleProcedure or surgery
The investigators will take a blood sample from the umbilical cord at birth and again at 9 years of age.
| Study group | Role | What they receive |
|---|---|---|
| Fetuses/Children with IUGR | The moving sequences of the heart movement are collected at the regular ultrasound examinations during pregnancy. Following delivery the investigators plan to examine the baby with cardiac ultrasound, echocardiography, between 12 and 72 hours after delivery and again when the child is 3-4 months old and at 9 years of age.
Blood sample will be taken from the umbilical cord at birth and again at 9 years of age. The investigators will analyse the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the children's DNA.
Due to corona pandemic the follow up was delayed from 7 to 9 years of age. Approved by the ethical committee. Receives: Other: Echocardiography; Procedure: Blood sample | |
| Healthy Controls | The moving sequences of the heart movement are collected at two occasions approximately 4 weeks apart. This takes place during gestational weeks 28-36. Following delivery the investigators plan to examine the baby with cardiac ultrasound, echocardiography, between 12 and 72 hours after delivery and again when the child is 3-4 months old and at 9 years of age.
Blood sample will be taken from the umbilical cord at birth and again at 9 years of age. The investigators will analyze the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the children's DNA.
Due to corona pandemic the follow up was delayed from 7 to 9 years of age. Approved by the ethical committee. Receives: Other: Echocardiography; Procedure: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Velocity of the Cardiac Walls cm/s Divided With Chamber Length in mm = Quota cm/s / mm
Echocardiography images of the heart's walls are outlined and the software extracts the movement in different directions. At each timepoint offline calculation were performed three times on each image and an averaged was calculated.
The length of the heart from the level of the AV valve to the apex in left ventricle is used as a measurement for the size of the heart.
As the velocity increases when the size of the heart increases a quota is used dividing the velocity by the length of the heart to be able to compare the velocity at different timepoints whe the child is growing.
Quota=Left chamber velocity at septum stated in cm/s divided by ventricular length in mm.
Measured: After delivery echocardiography were performed. This is one time point. Due to the known dramatic hemodynamic changes for all children right after birth we defined this time point to somewhere between 12 and 72 hours of age.
Secondary outcomes (7)
Left Chamber Longitudinal Displacement in the Septal Wall at the AV Valve Level Corrected for Ventricular Length Expressed as a Ratio.
Echocardiography images of the heart's walls are outlined and the software extracts the movement in mm in the myocardial wall from end diastole to end systole.
The movement of the myocardium from end diastole to end systole at the AV valve level of the septal wall is measured in mm and expressed as a ratio compared to the ventricular length in mm at the end of diastole.
Measured: After delivery echocardiography were performed. This is one time point. Due to the known dramatic hemodynamic changes for all children right after birth we defined this time point to somewhere between 12 and 72 hours of age.
Average Longitudinal 4 Segmental Strain in the Cardiac Wall. Shortening of the Myocardium in Systole.
Echocardiography images of the heart's walls are outlined and the software extracts the movement in different directions.
A 4 chamber view of the hartt is used and calculation of 6 segments (2 basal, 2 mid and 2 apical segments) were performed three times on each image and an averaged was calculated. The 2 basal segments closeset to the AV valve and the two 2 mid segments were summed and averaged into average longitudinal 4 segmental strain.
Strain in % is the averege shortening of the myocardium in systole.
Measured: At 3 months
Cardiac Marker Troponin T
Comparing cardiac marker troponin T between the two groups
Measured: At birth and at 9 years of age
Cardiac Marker N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)
Comparing N-terminal prohormone of brain natriuretic peptide marker NT-ProBNP between the two groups
Measured: At birth and at 9 years of age
Insulin-like Growth Factor-1 (IGF-1)
Comparing IGF-1 between the two groups
Measured: At birth and at 9 years of age
Insulin-like Growth Factor Binding Protein (IGFBP)
Comparing Insulin-like growth factor binding protein (IGFBP) between the two groups
Measured: At birth and at 9years of age
DNA Methylation and Gene Expression in Blood Monocytes and Lymphocytes
Changes in DNA methylation and gene expression will be compared between the two groups
Measured: At birth and at 9 years of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2015 (estimated)
- Study startJan 2013
- Primary completion30 Jun 2018
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for IUGRStudies of the same condition, open and under way.
- 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
- 61 participants (actual)
- Target duration
- 9 Years
Sponsor and investigators
- Lead sponsor
- University Hospital, Linkoeping
- Sponsor type
- University, hospital or other
- Collaborators
- Ostergotland County Council, Sweden, Stiftelsen Samariten
- Responsible party
- Principal investigator, Olov Änghagen, University Hospital, Linkoeping
- Investigators
- Olov Änghagen, PhD student, Principal investigator, Dept of Paediatric, LinköpingNina Nelson, Professor, Study chair, Karolinska University Hospital, StockholmPeter Bang, Professor, Study chair, Dept of Paediatric, LinköpingJan Engvall, Professor, Study chair, Dept of Clinical Physiology, LinköpingEva Nylander, Professor, Study chair, Dept of Clinical Physiology, Linköping
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02583763
- Sponsor's protocol ID
- 2012/257-31
- Acronym
- CADETTE
- Status last verified
- Mar 2025
- First submitted
- 16 Oct 2015
- Last updated
- 28 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Anghagen O, Engvall J, Gottvall T, Nelson N, Nylander E, Bang P. Developmental Differences in Left Ventricular Strain in IUGR vs. Control Children the First Three Months of Life. Pediatr Cardiol. 2022 Aug;43(6):1286-1297. doi: 10.1007/s00246-022-02850-y. Epub 2022 Mar 25.
PubMed 35333947
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Displacement From Third Trimester to Early Childhood
- ClinicalTrials.gov ID
- NCT02583763
- Acronym / sponsor ID
- CADETTE / 2012/257-31
- Keywords
- pro-brain natriuretic peptide (1-76), Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Echocardiography, Velocity Vector Imaging, Heart Function Tests
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 61 participants (actual)
- Lead sponsor
- University Hospital, LinkoepingUniversity, hospital or other
- Collaborators
- Ostergotland County Council, Sweden, Stiftelsen Samariten
- Study start
- Jan 2013 (actual)
- Primary completion
- 30 Jun 2018 (actual)
- Study completion
- Dec 2027 (estimated)
- First posted
- 22 Oct 2015 (estimated)
- Results
- Posted 28 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim is to increase awareness of the relationship between (IUGR) and cardiac function in the foetus, the development of cardiac function over time after delivery and what significance a possible early disturbed myocardial function have for the neonate and the child during the first years of life.
Detailed description
This is a prospective case-control study in which fetuses from normal pregnancies will be compared with fetuses with IUGR. Parents will be asked to participate in the study in connection with the routine ultrasound examinations at the department of obstetrics to where they have been referred because of suspected IUGR. The control group will be randomly selected among pregnant women who come for routine ultrasound during pregnancy at gestational week 18-20.
Surveys will be performed in the third trimester and after delivery. During the ultrasound examinations standardized, moving sequences of the heart will be saved. Analyses will be performed off-line and analysed by vector velocity imaging software. With this technique, the investigator can quantify the chamber wall and myocardial movements. Speed (velocity), movement (displacement) and thickening/deformation (strain and strain rate) will be recorded in a structured and standardized manner.
When performing the analysis the heart's walls are outlined and the software extracts the movement in different directions.
Data will be obtained concerning the participating mothers previous illness, mothers' age, maternal smoking, BMI, any abnormalities during pregnancy, number of previous pregnancies. Other data that will be recorded are means of delivery and any abnormalities during previous pregnancies, such as hypertension, preeclampsia and pre-natal steroid treatment.
Additional data to be collected from the participating fetuses are flow profiles in the umbilical artery, ductus venosus and middle cerebral artery. Abdominal circumference and estimated weight will be registered.
Following delivery, the participating child's height, weight, head circumference and gestational age at birth are registered. Additional data that will be collected after delivery are umbilical vein and umbilical artery acid base values, Apgar score. If admitted to the pediatric ward the investigators will register the number of days hospitalized in the ward for post-natal care and diagnosis. The investigators plan to examine the participating baby with cardiac ultrasound between 12 and 72 hours after delivery and again when the participating child is 3-4 months old and at 7-9 years of age.
The investigators will take a blood sample from the umbilical cord at birth and again at 7-9 years of age. The investigators will analyse the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the participating children's DNA.
Based on power calculation the investigators plan to examine between 20-30 fetuses with IUGR and 40-60 healthy fetuses in the control group.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 9 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fetuses/Children with IUGR | – | Other: Echocardiography, Procedure: Blood sampleThe moving sequences of the heart movement are collected at the regular ultrasound examinations during pregnancy. Following delivery the investigators plan to examine the baby with cardiac ultrasound, echocardiography, between 12 and 72 hours after delivery and again when the child is 3-4 months old and at 9 years of age. Blood sample will be taken from the umbilical cord at birth and again at 9 years of age. The investigators will analyse the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the children's DNA. Due to corona pandemic the follow up was delayed from 7 to 9 years of age. Approved by the ethical committee. |
| Healthy Controls | – | Other: Echocardiography, Procedure: Blood sampleThe moving sequences of the heart movement are collected at two occasions approximately 4 weeks apart. This takes place during gestational weeks 28-36. Following delivery the investigators plan to examine the baby with cardiac ultrasound, echocardiography, between 12 and 72 hours after delivery and again when the child is 3-4 months old and at 9 years of age. Blood sample will be taken from the umbilical cord at birth and again at 9 years of age. The investigators will analyze the blood for growth factors and cardiac markers. An additional ethical approval was accepted 2015 for analysing epigenetic factors in the children's DNA. Due to corona pandemic the follow up was delayed from 7 to 9 years of age. Approved by the ethical committee. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This is a prospective case-control study in which fetuses from normal pregnancies will be compared with fetuses with IUGR. Parents will be asked to participate in the study in connection with the routine ultrasound examinations at the department of obstetrics to where they have been referred because of suspected IUGR. The control group will be randomly selected among pregnant women who come for routine ultrasound during pregnancy at gestational week 18-20.
Key inclusion criteria (2 listed)
- Inclusion of research subjects: Growth restriction in routine pregnancy ultrasound, verified by specialist control. Gestational age based on Crown Rump Length measurements during the first trimester. Growth restriction defined by a deviation more than 22% from the normal curve at a given gestational age or growth rate deviates more than 10% compared to the previous measurement in relation to the expected weight.
- Inclusion of controls: Control individuals recruited among mothers who come to routine pregnancy ultrasound control at gestational week 18. These are randomly selected and then asked to participate.
Key exclusion criteria (1 listed)
- Exclusion of both the cases with IUGR and the control cases are major malformations, twin pregnancy, signs of intrauterine infection during pregnancy, significant illness or significant medical treatment of the mother.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EchocardiographyDuring the ultrasound examinations standardized, moving sequences of the heart will be saved. Analyzes are performed off-line and analyzed by vector velocity imaging software. | Other | Fetuses/Children with IUGR, Healthy Controls |
| Blood sampleThe investigators will take a blood sample from the umbilical cord at birth and again at 9 years of age. | Procedure or surgery | Fetuses/Children with IUGR, Healthy Controls |
Primary outcome
Velocity of the Cardiac Walls cm/s Divided With Chamber Length in mm = Quota cm/s / mm
Time frame: After delivery echocardiography were performed. This is one time point. Due to the known dramatic hemodynamic changes for all children right after birth we defined this time point to somewhere between 12 and 72 hours of age.
Echocardiography images of the heart's walls are outlined and the software extracts the movement in different directions. At each timepoint offline calculation were performed three times on each image and an averaged was calculated. The length of the heart from the level of the AV valve to the apex in left ventricle is used as a measurement for the size of the heart. As the velocity increases when the size of the heart increases a quota is used dividing the velocity by the length of the heart to be able to compare the velocity at different timepoints whe the child is growing. Quota=Left chamber velocity at septum stated in cm/s divided by ventricular length in mm.
7 secondary outcomes
Left Chamber Longitudinal Displacement in the Septal Wall at the AV Valve Level Corrected for Ventricular Length Expressed as a Ratio.
Time frame: After delivery echocardiography were performed. This is one time point. Due to the known dramatic hemodynamic changes for all children right after birth we defined this time point to somewhere between 12 and 72 hours of age.
Average Longitudinal 4 Segmental Strain in the Cardiac Wall. Shortening of the Myocardium in Systole.
Time frame: At 3 months
Cardiac Marker Troponin T
Time frame: At birth and at 9 years of age
Cardiac Marker N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)
Time frame: At birth and at 9 years of age
Insulin-like Growth Factor-1 (IGF-1)
Time frame: At birth and at 9 years of age
Insulin-like Growth Factor Binding Protein (IGFBP)
Time frame: At birth and at 9years of age
DNA Methylation and Gene Expression in Blood Monocytes and Lymphocytes
Time frame: At birth and at 9 years of age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35333947Anghagen O, Engvall J, Gottvall T, Nelson N, Nylander E, Bang P. Developmental Differences in Left Ventricular Strain in IUGR vs. Control Children the First Three Months of Life. Pediatr Cardiol. 2022 Aug;43(6):1286-1297. doi: 10.1007/s00246-022-02850-y. Epub 2022 Mar 25.
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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.
Olov Änghagen, PhD student principal investigator
Dept of Paediatric, Linköping
Nina Nelson, Professor study chair
Karolinska University Hospital, Stockholm
Peter Bang, Professor study chair
Dept of Paediatric, Linköping
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of IUGR and Fetal Growth Retardation, run by University Hospital, Linkoeping at 2 sites in Sweden.
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 1 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: under way, not looking for participants, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. 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?
Yes. Results are posted in the registry (first posted 28 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Velocity of the Cardiac Walls cm/s Divided With Chamber Length in mm = Quota cm/s / mm (time frame: After delivery echocardiography were performed. This is one time point. Due to the known dramatic hemodynamic changes for all children right after birth we defined this time point to somewhere between 12 and 72 hours of age.). 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 NCT02583763, which also lists 1 linked publication.
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 28 Mar 2025.