Abstract
ObjectivesExtremely preterm (EP) survivors have smaller brains, lower IQ, and worse educational achievement than their term-born peers. The contribution of smaller brain size to the IQ and educational disadvantages of EP is unknown. This study aimed (i) to compare brain volumes from multiple brain tissues and structures between EP-born (<28weeks) and term-born (≥37weeks) control adolescents, (ii) to explore the relationships of brain tissue volumes with IQ and basic educational skills and whether this differed by group, and (iii) to explore how much total brain tissue volume explains the underperformance of EP adolescents compared with controls.MethodsLongitudinal cohort study of 148 EP and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic resonance imaging-determined brain volumes of multiple tissues and structures were calculated. IQ and educational skills were measured using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT-4), respectively.ResultsBrain volumes were smaller in EP adolescents compared with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%] for total brain tissue volume). The largest relative differences were noted in the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]), spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of total brain tissue and other brain tissues and structures correlated positively with IQ and educational skills, a relationship that was similar for both the EP and controls. Total brain tissue volume explained between 20-40% of the IQ and educational outcome differences between EP and controls.ConclusionsEP adolescents had smaller brain volumes, lower IQs and poorer educational performance than controls. Brain volumes of multiple tissues and structures are related to IQ and educational outcomes. Smaller total brain tissue volume is an important contributor to the cognitive and educational underperformance of adolescents born EP.
Highlights
IntroductionCerebral white matter injury has long been recognised as the primary brain lesion affecting very preterm infants [1]
Preterm birth is associated with altered brain growth and development [1]
Of the 225 Extremely preterm (EP) and 253 control subjects known to be alive at 8 years, 176 (78%) EP and 155 (61%) controls were seen as part of the follow-up study at 18 years
Summary
Cerebral white matter injury has long been recognised as the primary brain lesion affecting very preterm infants [1]. There is increasing evidence of gray matter involvement due to secondary neuronal and axonal injury, prompting the term “encephalopathy of prematurity” to encompass pathology involving both white and gray matter [2,3]. Functional deficits in cognitive and educational domains in mid-childhood and adolescence have been reported in preterm cohorts worldwide [6]. In a comparative study of 4 countries, extremely low birthweight children were assessed between the ages of 8 to 11 years, and the proportion of the extremely low birthweight children who performed within the normal range for IQ and measures of educational skills were between 40 to 80%, with more than half the cohort requiring special educational assistance or repeating a grade at school [7]
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