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