WASHINGTON, DC—Between 5% and 15% of babies born prematurely later display major spastic motor deficits suggesting cerebral palsy. “Even more concerning is that between 25% and 50% of these infants will exhibit a broad range of developmental disabilities,” emphasized Terrie E. Inder, MD. Dr. Inder is a visiting scientist at Children’s Hospital in Boston and an Associate Professor at the University of Melbourne in Australia.

Suspecting that premature infants might have brain structure alterations relative to healthy term infants, Dr. Inder and colleagues used an advanced form of magnetic resonance imaging (MRI) to compare the two groups’ brain structures. “Based on previous neuropathologic and conventional data, we anticipated finding alterations principally in white matter structures,” Dr. Inder said. What she and her group discovered, however, was that the most striking differences between premature and term infants were in cortical gray matter, she related in her presentation at the 31st Annual Meeting of the Child Neurology Society.

MRI OF TWO INFANT COHORTS

The study included 100 consecutive very-low-birth-weight infants enrolled from November 1998 to December 2000 and 30 premature infants recruited from July to October 2001. These infants had a mean gestational age of 27.7 weeks and a mean birth weight of 1,033 g. Ninety percent of the infants received antenatal steroid therapy and about 75% required ventilatory support at birth. Some 25% were still on oxygen with bronchopulmonary dysplasia at 36 weeks gestational age equivalent.

During the week of their delivery due date, the infants underwent advanced quantitative volumetric three-dimensional MRI to allow measurement of their cerebral tissue volumes. Dr. Inder and colleagues recorded images of cortical gray matter, myelin, basal ganglia, and cerebrospinal fluid; 11 infants were subsequently excluded from the study because their MRI scans contained incomplete sequences or were obscured by motion artifact.

PREMATURITY AND BRAIN STRUCTURE

Compared with a group of 10 healthy term infants, the premature infants showed significant reductions in cortical gray matter volume on MRI; their myelin and total cerebral tissue volumes were also decreased. In contrast, their cerebrospinal fluid volume was significantly increased.

“We previously reported in a small series that the presence of periventricular white matter injury was associated with a reduction in cortical gray matter volume,” Dr. Inder pointed out. In the current study, the observed alterations in cortical gray matter and other types of cerebral tissue were indeed the greatest among the 20 premature infants with white matter injury. In a post hoc analysis, however, premature infants without evidence of white matter injury also showed significant reductions in cortical gray matter, myelin, total tissue volume, and the percentage of cortical gray matter within the intracranial cavity. Furthermore, when the investigators examined the relationships of approximately 50 variables to brain structure, immaturity was by far the most potent factor—other than cerebral injury—to be associated with the observed alterations.

After adjustment for infant body weight at the time of MRI, a strong link emerged between low birth weight and reduced cortical brain matter volume. Gestational age at birth and brain structure alteration were also significantly related, Dr. Inder reported.

The results of the study suggest that periventricular white matter injury is a major influence on subsequent brain development independent of gestation, whereas immaturity appears to be the main contributor to altered brain volume at term in premature infants without white matter injury. “This MRI study confirms a high incidence of altered brain development at term in an unselected population of premature infants,” concluded Dr. Inder. The question remains, however, whether the study findings explain the developmental disabilities that are so common in premature infants, she said.

NR

—Timothy Begany

Suggested Reading
Huppi PS, Inder TE. Magnetic resonance techniques in the evaluation of the perinatal brain: recent advances and future directions. Semin Neonatol. 2001;6:195-210.
Huppi PS, Murphy B, Maier SE, et al. Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging. Pediatrics. 2001;107:455-460.

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