Regional brain volume abnormalities and long-term cognitive outcome in preterm infants

Context Preterm infants have a high prevalence of long-term cognitive and b ehavioral disturbances. However, it is not known whether the stresses assoc iated 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 a nd preterm children and to examine the association of regional brain volume s in prematurely born children with long-term cognitive outcomes. Design and Setting Case-control study conducted in 1998 and 1999 at 2 US un iversity medical schools. Participants A consecutive sample of 25 eight-year-old preterm children rec ruited from a longitudinal follow-up study of preterm infants and 39 term c ontrol children who were recruited from the community and who were comparab le 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, der ived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cogn itive measures (at age 8 years) and perinatal variables among preterm child ren. 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 chil dren's brain volumes were significantly larger (by 105.7%-271.6%) in the oc cipital and temporal horns of the ventricles (P<.001 for all) and smaller i n the cerebellum (6.7%; P=.02), basal ganglia (11.4%-13.8%; P less than or equal to.005), amygdala (left, 20.2% [P=.001]; right, 30.0% [P<.001]), hipp ocampus (left, 16.0% [P=.001]; right, 12.0% [P=.007]), and corpus callosum (13.1%-35.2%; P less than or equal to.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 regiona lly specific, long-term reductions in brain volume and that morphological a bnormalities are, in turn, associated with poorer cognitive outcome.