Twin; Pregnancy, Affecting Fetus or NewbornCONTRASTNCT05952583
Selective Fetal Growth Restriction in Monochorionic Twins - an International Investigation
An observational study of Twin; Pregnancy, Affecting Fetus or Newborn and Fetal Growth Retardation, run by Leiden University Medical Center at 6 sites in 6 countries.
Trial summary
Optimal diagnostic management and underlying pathophysiological mechanisms of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies have not been fully clarified. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Twin; Pregnancy, Affecting Fetus or Newborn, Fetal Growth Retardation, Twin Monochorionic Diamniotic Placenta
- What is being tested?
- Ultrasound
- How many people
- 274 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 17 Feb 2023to 1 Mar 2028
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Study population: MCDA pregnancies complicated by sFGR pregnancies that meet the inclusion criteria.
Who may be able to join
- MCDA twin pregnancy
- Diagnosis of sFGR before 28+0 weeks of GA (independent of Doppler flows)
- Pregnant woman ≥ 18 years and able to consent
- Partner (who has (future) parental responsibility - if applicable) ≥ 18 years and able to consent
- Written informed consent of both parents (if applicable) for participation in the longitudinal follow-up until 2 years after birth)
Who cannot join
- The presence of lethal anomalies (one or both fetuses)
- Multiple pregnancy higher order than twins;
- TTTS/TAPS present at moment of sFGR diagnosis.
Trial locations and contacts
6 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
6 sites in 6 countries
United States1 site, 1 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Ali Javinani, MD, PhD, contraststudy@childrens.harvard.edu
Alireza Shamshirsaz, Professor, MD, PhD
Belgium1 site, 1 recruiting
- Recruiting
Universitaire Ziekenhuizen Leuven
Leuven, 3000
Liesbeth Lewi, MD phD
Canada1 site, 1 recruiting
- Recruiting
Mount Sinai Hospital
Toronto, Ontario, ON M5G 1X5
Shiri Shinar, MD PhD
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
Joanne Verweij, MD PhD
Spain1 site, 1 recruiting
- Recruiting
BCNatal
Barcelona, 08028
Mar Bennasar, MD PhD
Sweden1 site, 1 recruiting
- Not yet recruiting
Karolinska University Hospital
Stockholm, 17164 Solna
Lotta Herling, MD PhD
About this study
Optimal diagnostic management and underlying pathophysiological mechanisms of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies have not been fully clarified.
The current diagnostic classification system based on three different umbilical artery flow patterns has no increasing scale of severity and the predictive value is limited. Since there is no treatment available for sFGR, predicting fetal deterioration is key in preventing single or double fetal demise. Outcome prediction is furthermore important in the selection of cases that will be offered selective reduction (to provide the larger twin with better prospects), as well as determining monitor frequency and possible hospital admission. As outcome prediction is clinically challenging, patient counselling is too, and parents often encounter a great deal of uncertainty during the pregnancy.
Read more
Furthermore, little is known about the brain development of sFGR children (both during pregnancy and after birth). Moreover, the psychological impact of an sFGR pregnancy of the future parent)s) has not been studied before. The impact of these factors should be taken into account during patient counseling, which is currently not the case.
By our knowledge, this is the first international, multicenter, prospective cohort study on that will address the abovementioned questions and knowledge gaps in MCDA pregnancies complicated by selective fetal growth restriction.
Read the detailed description
Selective fetal growth restriction (sFGR) in monochorionic twins may negatively impact the pregnancy. There is a substantial risk of fetal deterioration resulting in (iatrogenic) preterm birth or even intrauterine demise of one, or both fetuses. There are important unresolved challenges on a diagnostic level and underlying pathophysiological mechanisms of sFGR have not been fully clarified.
The current diagnostic classification system based on three different umbilical artery flow patterns has no increasing scale of severity and the observed flow patterns may be volatile in nature. This hinders optimal diagnostic management and complicates outcome prediction as the survival outcome differs per umbilical artery flow type. Consequently, parents encounter a great deal of uncertainty during the pregnancy. Since there is no treatment available for sFGR, predicting fetal deterioration is key in preventing single or double demise.
By testing several predictors, the investigators are aiming to improve outcome prediction at the time of sFGR diagnosis. The investigators furthermore hypothesize that additional ultrasound parameters could be of benefit in making the current classification system more accurate and less variable. Extensive histological placental examinations will shine a light on microscopic abnormalities which can increase our knowledge of the pathophysiology. Examining neurodevelopment of sFGR twins at two years of age will additionally be of great value for our understanding of the impact of sFGR and contribute to adequate patient counselling. Our study will evaluate the impact of a sFGR pregnancy on parental mental health and parent-to-infant(s) attachment, which has not been carried out this extensively before.
- Conditions
- Twin; Pregnancy, Affecting Fetus or Newborn, Fetal Growth Retardation, Twin Monochorionic Diamniotic Placenta, Twin Diseases
- Being tested
- Ultrasound
- Keywords
- sFGR, sIUGR, selective fetal growth restriction
- Medical subject headings
- Fetal Growth Retardation, Diseases in Twins
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UltrasoundDiagnostic test
Additional ultrasound measurements during pregnancy
| Study group | Role | What they receive |
|---|---|---|
| sFGR cohort | Monochorionic diamniotic twin pregnancies complicated by sFGR (diagnosed before 28 weeks of gestational age) Receives: Diagnostic Test: Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome
The composite outcome consists of fetal single or double demise, including selective fetal reduction and/or an iatrogenic elective birth < 32 weeks of gestational age because of fetal distress).
Measured: 2 years
Secondary outcomes (4)
Ultrasound parameters
Explanatory analysis of ultrasound parameters over course of sFGR pregnancy
Measured: 2 years
Prenatal and postnatal attachment
Measured: 2 years
Post-traumatic stress
Measured: 2 years
PARCA-R evaluation
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2023
- Study start17 Feb 2023
- Primary completion1 Mar 2025 (estimated)
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Twin; Pregnancy, Affecting Fetus or NewbornStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe 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
- 274 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Universitaire Ziekenhuizen KU Leuven, Karolinska University Hospital, BCNatal Fetal Medicine Research Center, MOUNT SINAI HOSPITAL, Boston Children's Hospital
- Responsible party
- Principal investigator, ejtverweij, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05952583
- Sponsor's protocol ID
- CONTR
- Acronym
- CONTRAST
- Status last verified
- Apr 2024
- First submitted
- 11 Jul 2023
- Last updated
- 15 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Noll A, Javinani A, Slaghekke F, Haak MC, van Klink J, Van der Meeren L, Lopriore E, Russo F, Aertsen M, Shamshirsaz A, Shinar S, Bennasar M, Tiblad E, Herling L, Lewi L, Verweij EJ; CONTRAST Study Group. Predicting outcomes in selective fetal growth restriction of monoChOrioNic Twins: an inteRnAtional observational cohort STudy protocol (CONTRAST study). BMJ Open. 2026 Feb 24;16(2):e114000. doi: 10.1136/bmjopen-2025-114000.
PubMed 41734920
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selective Fetal Growth Restriction in Monochorionic Twins - an International Investigation
- ClinicalTrials.gov ID
- NCT05952583
- Acronym / sponsor ID
- CONTRAST / CONTR
- Conditions
- Twin; Pregnancy, Affecting Fetus or Newborn, Fetal Growth Retardation, Twin Monochorionic Diamniotic Placenta, Twin Diseases
- Keywords
- sFGR, sIUGR, selective fetal growth restriction
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 274 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Universitaire Ziekenhuizen KU Leuven, Karolinska University Hospital, BCNatal Fetal Medicine Research Center, MOUNT SINAI HOSPITAL, Boston Children's Hospital
- Study start
- 17 Feb 2023 (actual)
- Primary completion
- 1 Mar 2025 (estimated)
- Study completion
- 1 Mar 2028 (estimated)
- First posted
- 19 Jul 2023 (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.
Optimal diagnostic management and underlying pathophysiological mechanisms of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies have not been fully clarified.
The current diagnostic classification system based on three different umbilical artery flow patterns has no increasing scale of severity and the predictive value is limited. Since there is no treatment available for sFGR, predicting fetal deterioration is key in preventing single or double fetal demise. Outcome prediction is furthermore important in the selection of cases that will be offered selective reduction (to provide the larger twin with better prospects), as well as determining monitor frequency and possible hospital admission. As outcome prediction is clinically challenging, patient counselling is too, and parents often encounter a great deal of uncertainty during the pregnancy.
Furthermore, little is known about the brain development of sFGR children (both during pregnancy and after birth). Moreover, the psychological impact of an sFGR pregnancy of the future parent)s) has not been studied before. The impact of these factors should be taken into account during patient counseling, which is currently not the case.
By our knowledge, this is the first international, multicenter, prospective cohort study on that will address the abovementioned questions and knowledge gaps in MCDA pregnancies complicated by selective fetal growth restriction.
Detailed description
Selective fetal growth restriction (sFGR) in monochorionic twins may negatively impact the pregnancy. There is a substantial risk of fetal deterioration resulting in (iatrogenic) preterm birth or even intrauterine demise of one, or both fetuses. There are important unresolved challenges on a diagnostic level and underlying pathophysiological mechanisms of sFGR have not been fully clarified.
The current diagnostic classification system based on three different umbilical artery flow patterns has no increasing scale of severity and the observed flow patterns may be volatile in nature. This hinders optimal diagnostic management and complicates outcome prediction as the survival outcome differs per umbilical artery flow type. Consequently, parents encounter a great deal of uncertainty during the pregnancy. Since there is no treatment available for sFGR, predicting fetal deterioration is key in preventing single or double demise.
By testing several predictors, the investigators are aiming to improve outcome prediction at the time of sFGR diagnosis. The investigators furthermore hypothesize that additional ultrasound parameters could be of benefit in making the current classification system more accurate and less variable. Extensive histological placental examinations will shine a light on microscopic abnormalities which can increase our knowledge of the pathophysiology. Examining neurodevelopment of sFGR twins at two years of age will additionally be of great value for our understanding of the impact of sFGR and contribute to adequate patient counselling. Our study will evaluate the impact of a sFGR pregnancy on parental mental health and parent-to-infant(s) attachment, which has not been carried out this extensively before.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sFGR cohort | – | Diagnostic Test: UltrasoundMonochorionic diamniotic twin pregnancies complicated by sFGR (diagnosed before 28 weeks of gestational age) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- MCDA pregnancies complicated by sFGR pregnancies that meet the inclusion criteria.
Key inclusion criteria (5 listed)
- MCDA twin pregnancy
- Diagnosis of sFGR before 28+0 weeks of GA (independent of Doppler flows)
- Pregnant woman ≥ 18 years and able to consent
- Partner (who has (future) parental responsibility - if applicable) ≥ 18 years and able to consent
- Written informed consent of both parents (if applicable) for participation in the longitudinal follow-up until 2 years after birth)
Key exclusion criteria (3 listed)
- The presence of lethal anomalies (one or both fetuses)
- Multiple pregnancy higher order than twins;
- TTTS/TAPS present at moment of sFGR diagnosis.
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 |
|---|---|---|
| UltrasoundAdditional ultrasound measurements during pregnancy | Diagnostic test | sFGR cohort |
Primary outcome
Composite outcome
Time frame: 2 years
The composite outcome consists of fetal single or double demise, including selective fetal reduction and/or an iatrogenic elective birth < 32 weeks of gestational age because of fetal distress).
4 secondary outcomes
Ultrasound parameters
Time frame: 2 years
Prenatal and postnatal attachment
Time frame: 2 years
Post-traumatic stress
Time frame: 2 years
PARCA-R evaluation
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2024.
- Derived from this study: PubMed 41734920Noll A, Javinani A, Slaghekke F, Haak MC, van Klink J, Van der Meeren L, Lopriore E, Russo F, Aertsen M, Shamshirsaz A, Shinar S, Bennasar M, Tiblad E, Herling L, Lewi L, Verweij EJ; CONTRAST Study Group. Predicting outcomes in selective fetal growth restriction of monoChOrioNic Twins: an inteRnAtional observational cohort STudy protocol (CONTRAST study). BMJ Open. 2026 Feb 24;16(2):e114000. doi: 10.1136/bmjopen-2025-114000.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Twin; Pregnancy, Affecting Fetus or Newborn and Fetal Growth Retardation, run by Leiden University Medical Center at 6 sites in 6 countries.
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 5 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: looking for participants now, as of the sponsor's last update on 15 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Belgium, Canada, Netherlands, Spain and 1 more country. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne Noll, MD (+32 16 34 47 50, a.t.r.noll@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite outcome (time frame: 2 years). 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 NCT05952583, 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 15 Apr 2024.