Corrective cardiac surgery is not to blame, study suggests
WEDNESDAY, Nov. 7 (HealthDay News) -- Brain development is delayed in babies born with certain heart defects, new research shows.
The slowdown in brain development is similar to the delay found in premature infants, the researchers added.
Babies who require heart surgery have long been known to experience developmental delays, but whether the delays were due to the surgery or other factors has been in debate.
Now, a study published in the Nov. 8 issue of the New England Journal of Medicine shows that these brain abnormalities exist before the surgery.
"This is one of the first studies to say they have a true difference [in brain development] before they have surgery," says pediatric cardiologist Vidu Garg, assistant professor of pediatrics and molecular biology at the University of Texas Southwestern Medical Center and a pediatric cardiologist at Children's Medical Center, Dallas.
"It's been known that kids don't do well after open heart surgery. The relationship between congenital heart defects and brain development has not been known but has been hypothesized," said Garg, who was not involved in the study.
According to the U.S. National Institutes of Health, congenital heart defects cause more deaths among newborns than any other birth defects. Slightly less than one percent of American babies, or about 35,000 annually, have a congenital heart defect, according to the American Heart Association.
In the study, a team from the University of California, San Francisco, and at the University of British Columbia, Vancouver, examined 41 infants born with congenital heart disease. Twenty-nine had transposition of the great arteries and 12 had single-ventricle physiology. The researchers used magnetic resonance imaging (MRI) to analyze measures of brain development in each infant, including diffusivity and white-matter tracts.
White matter is the tissue through which nerve cells in the brain and nervous system communicate. Although the babies in the study had the same amount of white matter as babies without heart defects, the white matter was less mature and therefore at greater risk of injury, due to stressors like reduced blood oxygen levels. White-matter injury was observed in 13 of the 41 infants.
The team also found a decrease of 10 percent in the ratio of N-acetylaspartate (NAA) to choline, and an increase of 28 percent in the ratio of lactate to choline. These are surrogate measures for metabolic brain development, explained study co-researcher Dr. Patrick McQuillen. McQuillen practices Pediatric Critical Care Medicine and Pediatrics in San Francisco, California.
Previous studies have shown that lower levels of NAA and higher levels of lactate were associated with an increased risk of neurodevelopmental impairment in infancy and childhood.
The researchers also found an increase of 4 percent in what's knows as diffusivity, a measure of brain tissue structure. According to Miller, as a brain develops more complex tissues, there are usually more barriers to water diffusing through tissues, which means that diffusivity decreases with maturity.
Finally, babies with heart defects also displayed a decrease of 12 percent in white-matter fractional anisotropy, meaning the brain's white matter was less mature.
"White matter injury, the characteristic pattern of injury in the premature newborn, was surprisingly common in the newborns with heart disease that we studied," said study lead author Dr. Steven Miller, assistant professor of pediatrics at the University of British Columbia.
White matter does have some capacity to heal itself following injury, a process known as remyelination, which may involve injured cells repairing themselves or new cells being produced, the researchers said.
"It is very important to note that babies with heart disease have the potential for ongoing brain development and even recovery if there is injury," said McQuillen.
Better imaging technologies are helping identify babies with heart defects in utero, which means parents can plan for the birth at a facility that provides care and surgery to these infants. Many times, congenital heart defects are diagnosed soon after birth, said McQuillen. However, some infants still go home and become very ill before their condition is recognized, he added.
"Although we don't know the exact cause of delayed brain development, it is likely to relate to the way blood flows to the brain in fetal life. In babies with the two types of heart disease that we studied, the brain receives blood with lower oxygen," said McQuillen.
But questions remain, Garg said. Even though the study confirms that brain development delays exist prior to surgery, it does not settle the question of cause and effect, he said.
It's possible for heart defects and brain abnormalities to exist in the same population but not necessarily be related to each other, Garg argued.
"In the paper, they describe the abnormalities that have been seen. The question is whether [heart defects are] related to that. It's an association. Also, the kids have these abnormalities on MRI, but does this lead to later abnormalities? Further studies need to be done in terms of linking the two brain abnormalities," said Garg.
The researchers said further investigation is needed to find ways of minimizing brain development delays in utero and as a result of heart surgery.
Garg acknowledged that the new information may help physicians protect babies' brains before and during heart surgery, but those steps could have hazards of their own.
"We do a lot of interventions that can lead to neurologic problems. You have multiple hits, so how do you know what caused the developmental delay? That's what's tricky about it," Garg said.
The researchers did not compare the infants' brain development to that of other infants who are ill at birth, he added, and long-term studies of the impact of these brain abnormalities are needed.
"Babies with a fetal diagnosis may also be studied with MRI to learn more about how the brain develops when there is congenital heart disease. This will be especially important as cardiologists begin to consider interventions to treat heart conditions before birth -- something that is only being studied at this time," said McQuillen.
The researchers stressed that both of the congenital heart defects in the study required surgery. Parents who have been told their child has a heart murmur but does not need surgery should not worry about related developmental delays, McQuillen and Miller said.
There's more on congenital heart defects at the American Heart Association.
SOURCES: Vidu Garga, M.D., assistant professor, department of pediatrics and molecular biology, University of Texas Southwestern Medical cCenter, pediatric cardiologist at Childrens Medical Center, Dallas; Patrick S. McQuillen, department of pediatrics, University of California, San Francisco; Steven Miller, MDCM, assistant professor, pediatrics, division of neurology, BC Children's Hospital and Child & Family Research Institute, University of British Columbia, Vancouver, Canada; Nov. 8, 2007, New England Journal of Medicine
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