Prenatal Effects of Congenital Heart Disease (CHD) on Neurodevelopmental Outcome

Congenital heart disease (CHD) is the most common class of birth defect and is a major cause
of infant and child death and morbidity, including neurodevelopmental delay. Children with
severe forms of CHD are at high risk for a spectrum of neurocognitive difficulties that
include learning disability, attention deficit and hyperactivity disorder, behavioral
problems and mental retardation. The etiology of neurodevelopmental delay in children with
CHD is not fully understood but is thought to be secondary to a combination of pre- and
post-natal insults to the brain. It has been observed that fetuses with severe forms of CHD
have abnormal blood flow to the brain as measured by Doppler ultrasound. This
"centralization" or redirection of blood flow toward vital organs such as the brain has been
shown to lead to abnormal brain development in other fetal diseases, such as intrauterine
growth restriction. Evidence of the importance of prenatal brain development in the setting
of CHD is amounting. Neonates with complex CHD demonstrate abnormalities of brain structure
and blood flow prior to cardiothoracic surgery. However, to date, associations between
abnormal fetal brain blood flow and neonatal neurologic outcomes and brain function have not
been established in the CHD population. Finally, newborns with CHD have been shown to have
abnormalities in heart rate over a 24 hour period. This finding suggests that the autonomic
nervous system, which controls heart rate and blood pressure, may not function properly in
infants with CHD.

The study proposes that these changes in blood flows in the fetus with heart disease could
be responsible in part for poor brain growth, abnormal brain structure and function and
developmental delay in childhood. Investigators will use routine obstetrical ultrasound and
fetal echocardiograms to evaluate blood flow to vital organs and brain growth in fetuses
with CHD. Investigators will use non-invasive fetal monitors to measure fetal heart rate and
movement. Investigators will look at brain structure using Magnetic Resonance Imaging (MRI)
in the fetus and newborn. Afterbirth, investigators will use non-invasive monitors to
measure neonatal heart rate and blood pressure changes in response to a tilt, similar to
what is experienced when placing an infant in a car seat. Investigators will use a
non-invasive monitor consisting of a sticker applied to the skin to measure the level of
oxygen in the brain. Investigators will also measure brain function in the newborn with an
electroencephalogram(EEG) that records the electrical signaling between different parts of
the brain using a special plastic hat like a swim cap. Regular physical exams with a
pediatrician to measure growth and development will take place. A special test designed to
detect learning disabilities will also be done when the child is 14 months old. This test
will consist of talking with the child, reading stories, and showing the child pictures and
colors. There will be no extra blood tests needed and none of the tests pose any risk to the
mother, fetus, infant, or child.

The possible benefits to the child and the family will be early identification of any brain
abnormality in the newborn period as well as learning disabilities in the toddler which will
then allow the child to receive therapies designed to treat these problems. Studies show
that early identification and treatment of learning disabilities are important to enhance
the potential of the child.

Inclusion Criteria:

1. All women who present to Columbia University Medical Center between 18-24 wks
gestational age with the following fetal diagnoses will be invited to participate:

2. Hypoplastic Left Heart Syndrome (HLHS)

3. Transposition of the Great Arteries (TGA)

4. Tetralogy of Fallot (TOF)

5. Lung anomalies consisting of either congenital cystic adenomatoid malformations or
bronchogenic cysts

Exclusion Criteria:

1. Documented fetal chromosomal anomaly

2. Structural brain malformations

3. Evidence of placental insufficiency or Intrauterine growth retardation

4. Documented hydrops fetalis or sustained cardiac arrhythmias

5. Anticipated delivery at an outside hospital