Summer 2008

Link Between Congenital Heart Disease and Brain Injury

Neurodevelopmental outcome in children with congenital heart disease is a top priority for pediatric researchers at UCSF. Pediatric critical care specialist Patrick McQuillen, M.D., says that two-thirds of infants with congenital heart disease are found, via magnetic resonance imaging (MRI), to have brain injuries before or shortly after surgery. McQuillen and his colleagues are investigating the association of these brain injuries with subsequent neurodevelopmental outcome. Their goal is to devise prevention strategies in the near future.

"For many years, it was assumed that the brain injury occurred during surgery, but we and others have found that about one-third of the patients incur injury before surgery, with another third during or just after surgery," says McQuillen. "It's an interesting problem. The more we look, the more we learn and, in some ways, the more complicated the story gets. Yet the fact that we can even consider the issue reflects the results of tremendous strides made by pediatricians and heart surgeons that have saved the lives of babies with heart disease. What we are learning may benefit all sick children."

McQuillen says that not all heart defects cause brain injury and that children with heart murmurs or other simple defects, which may require surgery later in life, are not at risk. Nor are all the injuries severe; many are small and subtle. While there are many forms of congenital heart disease, two of the most common are transposition of the great arteries (TGA) and hypoplastic left heart syndrome (HLHS), and each shows unique types of injury and risk factors.

Following up on five years of this research, McQuillen currently performs pre- and post-operative MRIs in his studies of more than 100 babies. "The number of babies we have enrolled is a testament to the incredible generosity of patients, parents and families during a time of great stress," he says.

McQuillen plans to conduct neurodevelopmental assessments of these children at 12 months, 18 months and 3 years of age. The assessments include the Bayley Scales of Infant Development and formal IQ testing.

"In many ways, as these children grow up, they look like children who were born prematurely. They have problems with language, visual-spatial integration and motor function," says McQuillen. "Although these deficits span many areas, often they are not severe. The sooner parents know there is a problem, the sooner they can have the kids involved in early educational or physical therapy to overcome these issues."

McQuillen also looks at metabolic and microstructural development of the neonatal brain, using such advanced MR techniques as diffusion tensor imaging and magnetic resonance spectroscopy. With these techniques, his research group found that brain development appeared delayed—an observation that may explain the high frequency of small, focal injuries to the white matter that is more commonly seen in premature babies.

"We found that even before surgery, the brains of babies with congenital heart disease look about a month premature," says McQuillen. "We think their development is delayed by altered blood or oxygen delivery to the brain while in the womb. So, even though they are born at term, developmentally they may be at the same point as preemies."

Imaging Findings Inform Clinical Care

All aspects of the clinical care of infants with CHD and its association with brain injury are also being researched by McQuillen and colleagues. They found that one-half to two-thirds of patients with TGA who required balloon septostomy, a specific lifesaving procedure, prior to surgery developed a stroke. The group is currently devising a trial to determine whether routine anticoagulation with heparin, given during and around the time of the septostomy procedure, will prevent injury.

Other risk factors that have been identified include specific techniques of cardiopulmonary bypass during repair of HLHS and low blood pressure for any infant following surgery. These factors may also be suitable for interventional clinical trials.

In the future, McQuillen plans to extend these studies to the fetal period in an attempt to determine the safest time for performing lifesaving operations.

"Maybe the risk of brain injury is greater if we intervene during fetal life, rather than if we wait for the postnatal period or later in infancy," McQuillen says. "To begin to consider changes that may improve outcome, you have to first understand when specific injuries occur and how children do, from a neurodevelopmental outcome standpoint, with current practice. We have come so far that saving the lives of babies with heart disease is not enough. Now we want to maximize their quality of life."

For more information, contact Patrick McQuillen, M.D., at (415) 502-4798.

Related Information

News Releases

UCSF M.D. Wins Award for Infant Lung Treatment
John A. Clements, M.D., a professor of pediatrics emeritus at UCSF, has won the 2008 Pollin Prize for his contributions to the understanding of how lungs hold air and the development of a lifesaving treatment for respiratory distress syndrome in infants.

Research Provides Insight into
Brain Development

Research led by Anthony Wynshaw-Boris, M.D., Ph.D. — chief of pediatric Medical Genetics and a researcher in the Institute for Human Genetics at UCSF — may shed light on a rare pediatric disorder known as lissencephaly, or "smooth brain" disease.