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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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 Summary:

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 investigat
Sponsor: Catherine Cibulskis, MD

Current 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Developmental delay - 4 months [ Time Frame: 4 months of age ]
    Defined by delays of >1 month on physical therapy evaluation at 4 months of age
  • Developmental delay - 8 months [ Time Frame: 8 months of age ]
    Defined by delays of >1 month on physical therapy evaluation at 8 months of age
  • Neurodevelopmental impairment - 15 months [ Time Frame: 15 months of age ]
    Defined by mental, language, or physical developmental index < 2 standard deviations from the mean on the Bayley Scales of Infant Development III
  • MRI results [ Time Frame: Term gestational age ]
    Score on MRI, and pattern of MRI findings on donor and recipient twins when they reach term corrected gestational age


Original Secondary Outcome: Same as current

Information By: St. Louis University

Dates:
Date Received: September 15, 2014
Date Started: September 2014
Date Completion: September 2020
Last Updated: January 6, 2017
Last Verified: January 2017