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Bradley S. Peterson, MD; Betty Vohr, MD; Lawrence H. Staib, PhD; Christopher J. Cannistraci, BA; Aaron Dolberg, BA; Karen C. Schneider, MPH; Karol H. Katz, MS; Michael Westerveld, PhD; Sara Sparrow, PhD; Adam W. Anderson, PhD; Charles C. Duncan, MD; Robert W. Makuch, PhD; John C. Gore, PhD; Laura R. Ment, MD

JAMA. 2000;284:1939-1947.

Context  Preterm infants have a high prevalence of long-term cognitive and behavioral disturbances. However, it is not known whether the stresses associated with premature birth disrupt regionally specific brain maturation or whether abnormalities in brain structure contribute to cognitive deficits.

Objective  To determine whether regional brain volumes differ between term and preterm children and to examine the association of regional brain volumes in prematurely born children with long-term cognitive outcomes.

Design and Setting  Case-control study conducted in 1998 and 1999 at 2 US university medical schools.

Participants  A consecutive sample of 25 eight-year-old preterm children recruited from a longitudinal follow-up study of preterm infants and 39 term control children who were recruited from the community and who were comparable with the preterm children in age, sex, maternal education, and minority status.

Main Outcome Measures  Volumes of cortical subdivisions, ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala, and hippocampus, derived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cognitive measures (at age 8 years) and perinatal variables among preterm children.

Results  Regional cortical volumes were significantly smaller in the preterm children, most prominently in sensorimotor regions (difference: left, 14.6%; right, 14.3% [P<.001 for both]) but also in premotor (left, 11.2%; right, 12.6% [P<.001 for both]), midtemporal (left, 7.4% [P = .01]; right, 10.2% [P<.001]), parieto-occipital (left, 7.9% [P = .01]; right, 7.4% [P = .005]), and subgenual (left, 8.9% [P = .03]; right, 11.7% [P = .01]) cortices. Preterm children's brain volumes were significantly larger (by 105.7%-271.6%) in the occipital and temporal horns of the ventricles (P<.001 for all) and smaller in the cerebellum (6.7%; P = .02), basal ganglia (11.4%-13.8%; P.005), amygdala (left, 20.2% [P = .001]; right, 30.0% [P<.001]), hippocampus (left, 16.0% [P = .001]; right, 12.0% [P = .007]), and corpus callosum (13.1%-35.2%; P.01 for all). Volumes of sensorimotor and midtemporal cortices were associated positively with full-scale, verbal, and performance IQ scores (P<.01 for all).

Conclusions  Our data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome.

Author Affiliations: Child Study Center (Drs Peterson and Sparrow and Messrs Cannistraci and Dolberg) and Departments of Diagnostic Imaging (Drs Peterson, Staib, Anderson, and Gore), Epidemiology and Public Health (Dr Makuch and Ms Katz), Neurology (Dr Ment), Neurosurgery (Drs Duncan and Westerveld), and Pediatrics (Drs Westerveld and Ment and Ms Schneider), Yale University School of Medicine, New Haven, Conn; and Department of Pediatrics, Brown University School of Medicine, Providence, RI (Dr Vohr).

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