New Haven, Conn. – Brain scans of children born prematurely show key areas of the brain are much smaller than those of children born at full-term, a study by Yale researchers has found.
The researchers conducted magnetic resonance imaging (MRI) scans on 25 eight-year-olds born prematurely and compared them to brain scans of 39 children of comparable age, sex and maternal education.
The study published in the October 18 issue of the Journal of the American Medical Association is believed to be the first time brain volume has been measured in children born prematurely. It is also the first study to relate those abnormalities to cognitive outcome and perinatal risk factors.
"The differences in brain volume on average were dramatic in all regions, with reductions ranging from 11 percent to 35 percent," said Bradley Peterson, M.D., the House Jameson Associate Professor in Child Psychiatry at the Yale Child Study Center, associate professor in diagnostic radiology, and lead author of the study. "Not all children born prematurely showed these abnormalities, but those born at a younger gestational age were most affected. The magnitudes of the abnormalities in fact were directly proportional to how early the children were born, and they were strongly associated with IQ of the children at age eight years." The shortest gestation period for the children was 26 weeks.
The children born prematurely were followed since birth as a component of an ongoing study by Laura Ment, M.D., professor of pediatrics and neurology and senior investigator on the study.
"Premature birth at less than 1000 grams birth weight (approximately two pounds), is a major cause of developmental disability," Ment said. "Infants in this birth weight range represent almost one percent of all births in our country, and the survival rate for these infants is well over 80 percent. But the incidence of handicap is high."
"By age eight years, over 50 percent are in special education or receiving extensive resource room help," she said. "One-fifth have already repeated a grade of school. This study of very low birth weight infants who have been followed since six hours of age provides important insights into the adaptive mechanisms of the developing brain. From these studies, risk factors can be examined and interventions tested."
The brain volume in the children was measured on computer graphic work stations with fine grain manual definitions of regions of the brain. There were significant differences in the cortical subdivisions, ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala and hippocampus. Peterson said the size disparity was greatest in sensorimotor regions, as well as in premotor, midtemporal, parieto-occipital and subgenual cortices on both sides of the brain.
The size of sensorimotor and temporal cortices were associated with verbal and performance IQ scores. "The greater the volume of abnormalities, especially in the cortical regions, the lower the IQ measures," Peterson said.
He said the study would be useful from two perspectives.
"The study shows that when brains develop prematurely outside of the womb, they are vulnerable to developmental disturbances. We now need to find out what precisely is responsible for the problems with brain development in these infants – from a missing unidentified growth factor, to the absence of physiological buffering by the mother’s uterus, to the many medical problems associated with prematurity," Peterson said. "From a clinical standpoint, the results of this study show that we need to look earlier in life for the presence of these same abnormalities in prematurely born children so that we can identify for early therapeutic intervention those children who are at the greatest risk for the cognitive and behavioral difficulties that are associated with these disturbances in brain development."
The research was funded by the National Institute of Neurological Disorders and Stroke (NINDS), which is part of the National Institutes of Health, and the nation’s leading supporter of research on the brain and nervous system.
Giovanna Spinella, M.D., a program director from NINDS, said, "As more of the children from this study are imaged over time, we should be able to obtain even more information on regions of brain vulnerability, cognition and behavior of very premature infants as they mature into childhood and adolescence. Our ultimate goal is to be able to protect infant brains from injuries associated with prematurity, as well as to intervene and effectively treat the various cognitive and behavioral impairments."
The other Yale researchers on the study were Lawrence Staib, associate professor of diagnostic radiology and electrical engineering; Christopher Cannistraci, research assistant, diagnostic radiology; Aaron Dolberg and Karen Schneider, associate research scientists, pediatrics; Karol Katz, program analyst, Department of Epidemiology and Public Health; Michael Westerveld, associate professor neurosurgery; Sara Sparrow, psychology professor and professor and chief psychologist Child Study Center; Adam Anderson, assistant professor diagnostic radiology and applied physics; Charles Duncan, professor neurosurgery and pediatrics; and Robert Makuch, professor and division head public health biostatistics, and John Gore, professor of diagnostic radiology and applied physics. Betty Vohr, M.D., of Brown University School of Medicine, professor of pediatrics, also was a researcher on the study.
Journal
JAMA