The Utility of MRI Scoring to Predict Neurodevelopmental Outcomes in Survivors of Twin-to-Twin Transfusion Syndrome

Brief Title

The Utility of MRI Scoring to Predict Neurodevelopmental Outcomes in Survivors of Twin-to-Twin Transfusion Syndrome

Official Title

The Utility of MRI Scoring to Predict Neurodevelopmental Outcomes in Survivors

Brief 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. 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

      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 Type


Primary Outcome

Composite outcome of neurodevelopmental impairment - final

Secondary Outcome

 Developmental delay - 4 months


Fetofetal Transfusion

Study Arms / Comparison Groups

 Survivors of TTTS
Description:  Infants who have survived TTTS to hospital discharge, have an MRI at term, and return for nursery follow-up clinic.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

September 2014

Completion Date

May 2023

Primary Completion Date

September 30, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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




N/A - 3 Years

Accepts Healthy Volunteers



Catherine Cibulskis, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Catherine Cibulskis, MD


 St. Louis University

Study Sponsor

Catherine Cibulskis, MD, Principal Investigator, St. Louis University

Verification Date

May 2022