Cerebral Volume Reductions and Gray/White Tissue Differences In Preterm Children


Preterm birth is often characterized by an increased risk for developmental brain abnormalities as well as cognitive, physical,emotional and behavioral deficits. Differences in brain morphology may contribute to these outcomes. Our study attempted to determine how brain development differs among preterm children compared to term.


High-resolution MRI scans from 66 eight-year old preterm and 31 term children were obtained using a 1.5T GE scanner. Groups were matched for gender, ethnicity, SES, height and weight. MRI scans were imported into BrainImage (Stanford University,Stanford,CA) for semi-automated whole brain segmentation and quantification in the sagittal plane using previously described and validated methods [1].


Non-brain tissue is removed using a semi-automated process. The remaining brain tissue (gray scale image) is then segmented into gray matter, white matter and CSF using a fuzzy tissue segmentation algorithm.


Each brain was divided into cerebral lobes, subcortical nuclei, cerebellum, and lateral ventricles with a semiautomated, stereotactic-based parcellation method. This figure shows a statistical representation of gray matter in multi-planar views in BrainImage. Voxel shade represents the proportion of gray tissue (darker = increased). The Talairach [2] grid is shown by both dotted and solid lines. The sectors corresponding to the frontal lobe are outlined in solid lines.

The brain was divided based on the rater's identification of three anchor points:the anterior commisure,the posterior commisure,and a midsagittal point above the axis created by the first two points. Raters who conducted morphometric analyses were blind to the diagnosis of each subject. Interrater reliability obtained by interclass correlation exceeded 0.95.


As expected, males had larger cerebral volumes than females across groups. Between group comparisons showed that cerebral volumes were significantly reduced in preterm children compared to term children, irrespective of gender, IQ, and age.


Cerebral tissue volumes in cubic centimeters (cm 3 ). Preterm (PT)children have significantly reduced brain volumes compared to term (T) children. Males (M) have larger cerebral volumes than females (F ) across groups.


Mean cerebral white matter volumes in cubic centimeters (cm 3 ). This graph demonstrates
the significant gender by diagnosis effect with the relative white matter volume of preterm (PT) males being significantly reduced compared with term (T) males.

Additionally,compared with term children,the preterm group demonstrated disproportionately decreased total, gray and white matter temporal lobe volumes and disproportionately increased frontal gray, parietal total tissue and parietal gray matter volumes.


Regional brain volume differences in the preterm group compared with the term group.


Lateral ventricular enlargement and decreased subcortical gray matter volume, disproportionate to overall cerebral gray matter reduction, were also observed in the preterm group.


Preterm birth appears to have a significant effect on brain development, with increased risk for reduced cerebral and subcortical volumes and increased lateral ventricular CSF. A new and potentially important finding of this study is that males appear to be particularly vulnerable to adverse effects of preterm birth on white matter development. A possible implication of the differential effect of preterm birth on male neuroanatomy relates to clinical outcome. Very low birth weight males tend to have higher mortality rates than females. Additionally, surviving preterm males often demonstrate increased risk for physical, developmental, learning, and behavioral difficulties compared with females [3-5 ].


  1. Kates WR,Warsofsky IS,Patwardhan A,et al., "Automated Talairach atlas-based parcellation and measurement of cerebral lobes in children." Psychiatry Res, 1999. 91:11-30.
  2. Talairach JT, "Co-Planar Stereotaxic Atlas of the Human Brain Atlas." 1988, New York.
  3. Paneth N, et al., "Newborn intensive care and neonatal mortality in low-birth-weight infants:a population study." N Engl J Med, 1982. 307(3):149-55.
  4. Verloove-Vanhorick SP,et al., "Sex difference in disability and handicap at five years of age in children born at very short gestation." Pediatrics, 1994. 93(4):576-9.
  5. Hoffman EL and Bennett FC, "Birth weight less than 800 grams: changing outcomes and influences of gender and gestation number. Pediatrics." 1990. 86(1):27-34.

Kesler, SR, Reiss, AL, Pajot SK & Ment, LR. Cerebral Volume Reductions And Gray/White Tissue Differences In Preterm Children. 32nd Annual Meeting of the Society for Neuroscience, Orlando, FL, November 2-7, 2002: Poster.