Fetofetal TransfusionNCT02249624
The Utility of MRI Scoring to Predict Neurodevelopmental Outcomes in Survivors of Twin-to-Twin Transfusion Syndrome
An observational study of Fetofetal Transfusion, run by Catherine Cibulskis, MD at 1 site in United States.
Trial summary
Twins who share a placenta but have two separate sacs of amniotic fluid (monochorionic-diamniotic) are at risk of developing twin-to-twin transfusion syndrome (TTTS). TTTS results from anastomoses in the placenta that lead to unequal sharing of blood, causing abnormal blood flow to the twins. Read more about this study
- Who is it for?
- Ages Up to 3 years
- Conditions the study is for
- Fetofetal Transfusion
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to 30 May 2024
- 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 Up to 3 years
- All sexes
- No healthy volunteers
- Child
Study population: Pregnancies affected by TTTS will be identified through referrals from the St. Louis Fetal Care Institute. Surviving infants of those pregnancies that required fetal laser surgery, or had death of the cotwin, will be approached for enrollment.
Who may be able to join
- Infants who suffered from TTTS in utero that either required fetal laser photocoagulation or had death of their cotwin
- Born after implementation of our TTTS protocol in September 2013
- Complete postnatal MRI and follow-up at Cardinal Glennon Children's Medical Center, or at an outside hospital and release medical information to the study
Who cannot join
- Infants who did not have TTTS, or not severe enough to warrant fetal intervention or demise of the cotwin
- Infants who do not complete their follow-up per protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
About this study
Official title: The Utility of MRI Scoring to Predict Neurodevelopmental Outcomes in Survivors
Twins who share a placenta but have two separate sacs of amniotic fluid (monochorionic-diamniotic) are at risk of developing twin-to-twin transfusion syndrome (TTTS). TTTS results from anastomoses in the placenta that lead to unequal sharing of blood, causing abnormal blood flow to the twins. The donor twin may have low fluid levels, poor growth, and anemia. The recipient twin can have high fluid levels, high red blood cell counts, heart failure, and hydrops. Having TTTS, especially if there is demise of one twin or if disease is severe enough to warrant laser photocoagulation of the anastomotic sites, puts the surviving fetuses at risk for brain injury due to hypoxia, ischemia, or reperfusion injuries. Magnetic Resonance Imaging (MRI) is superior to ultrasound at detecting subtle cerebral injuries. An MRI scoring scale has been developed for use in very low birth weight infants that has been shown to correlate with neurodevelopmental outcomes, but it has not been tested in this patient population.
Our center's guidelines recommend fetal MRI prior to intervention, at 32 weeks gestational age, and on the infants at term corrected gestational age. Infants who were treated for TTTS in utero are seen in Nursery Follow-up Clinic at 4 months of age, 8 months of age, and for Bayley Scales evaluations at 15-18 months of age and at 2-3 years of age.
The purpose of this study is to correlate brain MRI score with neurodevelopmental outcomes in survivors of TTTS that have either required fetal surgical intervention or had demise of their cotwin. The investigators predict that more severe white and gray matter injury as determined by the Woodward/Inder grading scale will be positively associated with worse neurodevelopmental outcomes.
Read the detailed description
All mothers with a pregnancy affected by twin-to-twin transfusion syndrome (TTTS) who are referred to the St. Louis Fetal Care Institute (FCI) will be evaluated for enrollment over a two year period. The women who have severe findings that indicate a need for fetal intervention or who had demise of one fetus due to TTTS will be approached at FCI to discuss the study. Once the baby(ies) is/are born, written consent for the infant's participation will be obtained.
FCI and Cardinal Glennon Children's Medical Center have an established protocol for TTTS. Fetuses affected by TTTS under fetal MRI and echocardiogram at the time of diagnosis (if time permits before intervention) and again at 32 weeks of gestation. The infants receive a postnatal MRI at term corrected gestational age (>37 weeks of gestation). This may be done as an inpatient if they are still hospitalized at Cardinal Glennon, or as an outpatient if their birth hospitalization was at a different hospital, or if they are discharged to home prior to 37 weeks of age. They also receive a postnatal echocardiogram, which may be done during the birth hospitalization, or at the time of their outpatient MRI appointment. All of the infants are followed at 4-6 months of age for physical therapy evaluation, and if there are concerns, they return 4 months later for a repeat physical therapy evaluation. Bayley Scales of Infant Development (BSID-III) evaluations are performed by a child psychologist at 15-18 months corrected age, and again between 2-3 years of age. At any time in this process, if there are concerns about developmental progress, home therapy services are prescribed to help improve outcomes.
This protocol of evaluations results in a total of 3-5 follow-up appointments for each infant after initial hospital discharge, and are all standard of care at the investigators hospital.
MRI provides more detailed information than ultrasound in diagnosing hypoxic ischemic brain damage both prenatally and postnatally (1,2). Ultrasound has low sensitivity to detect non-hemorrhagic brain injuries, and studies have shown that only 14-27% of infants with cerebral injury on MRI had any abnormalities seen on head ultrasound(3,4).
Studies in premature infants have shown a correlation between MRI findings at term corrected age and neurodevelopmental outcomes. A grading scale has been proposed by Woodward and Inder to assess the degree of white and gray matter injury on MRI(5-7). After multivariate adjustment, this scale showed that increasing severity of white matter abnormalities was associated with increased risks of severe motor delay and cerebral palsy (5). The presence of any white matter abnormalities was found to be more sensitive at identifying children who had neurodevelopmental impairments than ultrasound findings of intraventricular hemorrhage or periventricular leukomalacia(5). Furthermore, most children with a normal or only mildly abnormal MRI were free of severe impairments at 2 years of age(5).
If infants at highest risk of neurodevelopmental delays could be identified earlier and more accurately, these infants could be monitored more closely and earlier interventions could be administered. This would potentially result in better long-term neurodevelopmental outcomes for these high-risk children. However, there is currently no correlative data between MRI findings and long-term neurodevelopmental outcomes in the survivors of TTTS.
- Conditions
- Fetofetal Transfusion
- Keywords
- Twin to twin transfusion syndrome, Developmental disabilities, Magnetic resonance imaging
- Medical subject headings
- Fetofetal Transfusion, Developmental Disabilities
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 |
|---|---|---|
| Survivors of TTTS | Infants who have survived TTTS to hospital discharge, have an MRI at term, and return for nursery follow-up clinic. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome of neurodevelopmental impairment - final
Defined by mental, language, or physical developmental index < 2 standard deviations from the mean on the Bayley Scales of Infant Development III, neurosensory impairment (hearing loss requiring aids or blindness), or the diagnosis of cerebral palsy.
Measured: 3 years of age
Secondary outcomes (4)
Developmental delay - 4 months
Defined by delays of >1 month on physical therapy evaluation at 4 months of age
Measured: 4 months of age
Developmental delay - 8 months
Defined by delays of >1 month on physical therapy evaluation at 8 months of age
Measured: 8 months of age
Neurodevelopmental impairment - 15 months
Defined by mental, language, or physical developmental index < 2 standard deviations from the mean on the Bayley Scales of Infant Development III
Measured: 15 months of age
MRI results
Score on MRI, and pattern of MRI findings on donor and recipient twins when they reach term corrected gestational age
Measured: Term gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion30 Sep 2020
- Study completion30 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Fetofetal TransfusionStudies 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 only
- Time perspective
- Prospective
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Cibulskis, MD
- Sponsor type
- University, hospital or other
- Collaborators
- St. Louis University
- Responsible party
- Sponsor-investigator, Catherine Cibulskis, MD, St. Louis University
- Investigators
- Catherine Cibulskis, MD, Principal investigator, St. Louis University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02249624
- Sponsor's protocol ID
- 23854
- Status last verified
- Jun 2024
- First submitted
- 15 Sep 2014
- Last updated
- 24 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Simonazzi G, Segata M, Ghi T, Sandri F, Ancora G, Bernardi B, Tani G, Rizzo N, Santini D, Bonasoni P, Pilu G. Accurate neurosonographic prediction of brain injury in the surviving fetus after the death of a monochorionic cotwin. Ultrasound Obstet Gynecol. 2006 May;27(5):517-21. doi: 10.1002/uog.2701.
PubMed 16586472Righini A, Kustermann A, Parazzini C, Fogliani R, Ceriani F, Triulzi F. Diffusion-weighted magnetic resonance imaging of acute hypoxic-ischemic cerebral lesions in the survivor of a monochorionic twin pregnancy: case report. Ultrasound Obstet Gynecol. 2007 Apr;29(4):453-6. doi: 10.1002/uog.3967.
PubMed 17390325Merhar SL, Kline-Fath BM, Meinzen-Derr J, Schibler KR, Leach JL. Fetal and postnatal brain MRI in premature infants with twin-twin transfusion syndrome. J Perinatol. 2013 Feb;33(2):112-8. doi: 10.1038/jp.2012.87. Epub 2012 Jun 28.
PubMed 22743408Inder TE, Anderson NJ, Spencer C, Wells S, Volpe JJ. White matter injury in the premature infant: a comparison between serial cranial sonographic and MR findings at term. AJNR Am J Neuroradiol. 2003 May;24(5):805-9.
PubMed 12748075Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med. 2006 Aug 17;355(7):685-94. doi: 10.1056/NEJMoa053792.
PubMed 16914704Inder TE, Wells SJ, Mogridge NB, Spencer C, Volpe JJ. Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study. J Pediatr. 2003 Aug;143(2):171-9. doi: 10.1067/S0022-3476(03)00357-3.
PubMed 12970628Woodward LJ, Mogridge N, Wells SW, Inder TE. Can neurobehavioral examination predict the presence of cerebral injury in the very low birth weight infant? J Dev Behav Pediatr. 2004 Oct;25(5):326-34. doi: 10.1097/00004703-200410000-00004.
PubMed 15502549
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Utility of MRI Scoring to Predict Neurodevelopmental Outcomes in Survivors
- ClinicalTrials.gov ID
- NCT02249624
- Acronym / sponsor ID
- 23854
- Conditions
- Fetofetal Transfusion
- Keywords
- Twin to twin transfusion syndrome, Developmental disabilities, Magnetic resonance imaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Catherine Cibulskis, MDUniversity, hospital or other
- Collaborators
- St. Louis University
- Study start
- Sep 2014
- Primary completion
- 30 Sep 2020 (actual)
- Study completion
- 30 May 2024 (actual)
- First posted
- 25 Sep 2014 (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.
Twins who share a placenta but have two separate sacs of amniotic fluid (monochorionic-diamniotic) are at risk of developing twin-to-twin transfusion syndrome (TTTS). TTTS results from anastomoses in the placenta that lead to unequal sharing of blood, causing abnormal blood flow to the twins. The donor twin may have low fluid levels, poor growth, and anemia. The recipient twin can have high fluid levels, high red blood cell counts, heart failure, and hydrops. Having TTTS, especially if there is demise of one twin or if disease is severe enough to warrant laser photocoagulation of the anastomotic sites, puts the surviving fetuses at risk for brain injury due to hypoxia, ischemia, or reperfusion injuries. Magnetic Resonance Imaging (MRI) is superior to ultrasound at detecting subtle cerebral injuries. An MRI scoring scale has been developed for use in very low birth weight infants that has been shown to correlate with neurodevelopmental outcomes, but it has not been tested in this patient population.
Our center's guidelines recommend fetal MRI prior to intervention, at 32 weeks gestational age, and on the infants at term corrected gestational age. Infants who were treated for TTTS in utero are seen in Nursery Follow-up Clinic at 4 months of age, 8 months of age, and for Bayley Scales evaluations at 15-18 months of age and at 2-3 years of age.
The purpose of this study is to correlate brain MRI score with neurodevelopmental outcomes in survivors of TTTS that have either required fetal surgical intervention or had demise of their cotwin. The investigators predict that more severe white and gray matter injury as determined by the Woodward/Inder grading scale will be positively associated with worse neurodevelopmental outcomes.
Detailed description
All mothers with a pregnancy affected by twin-to-twin transfusion syndrome (TTTS) who are referred to the St. Louis Fetal Care Institute (FCI) will be evaluated for enrollment over a two year period. The women who have severe findings that indicate a need for fetal intervention or who had demise of one fetus due to TTTS will be approached at FCI to discuss the study. Once the baby(ies) is/are born, written consent for the infant's participation will be obtained.
FCI and Cardinal Glennon Children's Medical Center have an established protocol for TTTS. Fetuses affected by TTTS under fetal MRI and echocardiogram at the time of diagnosis (if time permits before intervention) and again at 32 weeks of gestation. The infants receive a postnatal MRI at term corrected gestational age (>37 weeks of gestation). This may be done as an inpatient if they are still hospitalized at Cardinal Glennon, or as an outpatient if their birth hospitalization was at a different hospital, or if they are discharged to home prior to 37 weeks of age. They also receive a postnatal echocardiogram, which may be done during the birth hospitalization, or at the time of their outpatient MRI appointment. All of the infants are followed at 4-6 months of age for physical therapy evaluation, and if there are concerns, they return 4 months later for a repeat physical therapy evaluation. Bayley Scales of Infant Development (BSID-III) evaluations are performed by a child psychologist at 15-18 months corrected age, and again between 2-3 years of age. At any time in this process, if there are concerns about developmental progress, home therapy services are prescribed to help improve outcomes.
This protocol of evaluations results in a total of 3-5 follow-up appointments for each infant after initial hospital discharge, and are all standard of care at the investigators hospital.
MRI provides more detailed information than ultrasound in diagnosing hypoxic ischemic brain damage both prenatally and postnatally (1,2). Ultrasound has low sensitivity to detect non-hemorrhagic brain injuries, and studies have shown that only 14-27% of infants with cerebral injury on MRI had any abnormalities seen on head ultrasound(3,4).
Studies in premature infants have shown a correlation between MRI findings at term corrected age and neurodevelopmental outcomes. A grading scale has been proposed by Woodward and Inder to assess the degree of white and gray matter injury on MRI(5-7). After multivariate adjustment, this scale showed that increasing severity of white matter abnormalities was associated with increased risks of severe motor delay and cerebral palsy (5). The presence of any white matter abnormalities was found to be more sensitive at identifying children who had neurodevelopmental impairments than ultrasound findings of intraventricular hemorrhage or periventricular leukomalacia(5). Furthermore, most children with a normal or only mildly abnormal MRI were free of severe impairments at 2 years of age(5).
If infants at highest risk of neurodevelopmental delays could be identified earlier and more accurately, these infants could be monitored more closely and earlier interventions could be administered. This would potentially result in better long-term neurodevelopmental outcomes for these high-risk children. However, there is currently no correlative data between MRI findings and long-term neurodevelopmental outcomes in the survivors of TTTS.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Survivors of TTTS | – | –Infants who have survived TTTS to hospital discharge, have an MRI at term, and return for nursery follow-up clinic. |
Who may qualify
- Ages
- Up to 3 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Pregnancies affected by TTTS will be identified through referrals from the St. Louis Fetal Care Institute. Surviving infants of those pregnancies that required fetal laser surgery, or had death of the cotwin, will be approached for enrollment.
Key inclusion criteria (3 listed)
- Infants who suffered from TTTS in utero that either required fetal laser photocoagulation or had death of their cotwin
- Born after implementation of our TTTS protocol in September 2013
- Complete postnatal MRI and follow-up at Cardinal Glennon Children's Medical Center, or at an outside hospital and release medical information to the study
Key exclusion criteria (2 listed)
- Infants who did not have TTTS, or not severe enough to warrant fetal intervention or demise of the cotwin
- Infants who do not complete their follow-up per protocol
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
Composite outcome of neurodevelopmental impairment - final
Time frame: 3 years of age
Defined by mental, language, or physical developmental index < 2 standard deviations from the mean on the Bayley Scales of Infant Development III, neurosensory impairment (hearing loss requiring aids or blindness), or the diagnosis of cerebral palsy.
4 secondary outcomes
Developmental delay - 4 months
Time frame: 4 months of age
Developmental delay - 8 months
Time frame: 8 months of age
Neurodevelopmental impairment - 15 months
Time frame: 15 months of age
MRI results
Time frame: Term gestational age
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 24 Jun 2024.
- Background: PubMed 16586472Simonazzi G, Segata M, Ghi T, Sandri F, Ancora G, Bernardi B, Tani G, Rizzo N, Santini D, Bonasoni P, Pilu G. Accurate neurosonographic prediction of brain injury in the surviving fetus after the death of a monochorionic cotwin. Ultrasound Obstet Gynecol. 2006 May;27(5):517-21. doi: 10.1002/uog.2701.
- Background: PubMed 17390325Righini A, Kustermann A, Parazzini C, Fogliani R, Ceriani F, Triulzi F. Diffusion-weighted magnetic resonance imaging of acute hypoxic-ischemic cerebral lesions in the survivor of a monochorionic twin pregnancy: case report. Ultrasound Obstet Gynecol. 2007 Apr;29(4):453-6. doi: 10.1002/uog.3967.
- Background: PubMed 22743408Merhar SL, Kline-Fath BM, Meinzen-Derr J, Schibler KR, Leach JL. Fetal and postnatal brain MRI in premature infants with twin-twin transfusion syndrome. J Perinatol. 2013 Feb;33(2):112-8. doi: 10.1038/jp.2012.87. Epub 2012 Jun 28.
- Background: PubMed 12748075Inder TE, Anderson NJ, Spencer C, Wells S, Volpe JJ. White matter injury in the premature infant: a comparison between serial cranial sonographic and MR findings at term. AJNR Am J Neuroradiol. 2003 May;24(5):805-9.
- Background: PubMed 16914704Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med. 2006 Aug 17;355(7):685-94. doi: 10.1056/NEJMoa053792.
- Background: PubMed 12970628Inder TE, Wells SJ, Mogridge NB, Spencer C, Volpe JJ. Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study. J Pediatr. 2003 Aug;143(2):171-9. doi: 10.1067/S0022-3476(03)00357-3.
- Background: PubMed 15502549Woodward LJ, Mogridge N, Wells SW, Inder TE. Can neurobehavioral examination predict the presence of cerebral injury in the very low birth weight infant? J Dev Behav Pediatr. 2004 Oct;25(5):326-34. doi: 10.1097/00004703-200410000-00004.
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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.
Catherine Cibulskis, MD principal investigator
St. Louis University
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 Fetofetal Transfusion, run by Catherine Cibulskis, MD at 1 site in United States.
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 3 inclusion and 2 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 24 Jun 2024. 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 United States. 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?
Composite outcome of neurodevelopmental impairment - final (time frame: 3 years 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 NCT02249624, which also lists 7 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 24 Jun 2024.