By Matthew T. McCarthy, MD, and Barry E. Kosofsky, MD, PhD
Dr. McCarthy is Resident, Department of Pediatric Neurology, New York-Presbyterian Hospital/Weill Cornell Medical College. Dr. Kosofsky is Chief, Division of Pediatric Neurology, Goldsmith Professor of Pediatrics, Neurology and Neuroscience, and Radiology, Weill Cornell Medical College
Dr. McCarthy and Dr. Kosofsky report no financial relationships relevant to this field of study.
SYNOPSIS: Neonatal brain MRI can identify structural changes that predict future difficulties in school performance for children who are born preterm.
SOURCE: Ullman H, et al. Neonatal MRI is associated with future cognition and academic achievement in preterm children. Brain 2015;138(Pt 11):3251-3262.
With the number of children born prematurely continuing to grow, and with an increase in survival and decrease in medical complications in neonates born at earlier gestational ages, it is important to understand the long-term consequences of premature birth. It is well known that the more premature an infant, the higher the likelihood that the child will experience greater cognitive and academic difficulties relative to their peers born at term. This discrepancy usually persists throughout school years. This is particularly true for mathematics, with 10-18% of preterm children experiencing significant mathematical impairment and as many as two-thirds experiencing mild mathematical impairment. Underachievement in mathematics can have a long-term impact on school completion, eventual employment, and overall emotional and mental well-being. Therefore, it is important to discover factors that will help predict poor academic performance for preterm newborns to identify children at risk as early as possible to ensure that proper surveillance and appropriate interventions are provided in a timely manner.
The authors of this study investigated whether structural features detected on magnetic resonance imaging (MRI) performed on a cohort of Australian children born preterm (224 infants born < 30 weeks’ gestational age and/or < 1250 g birth weight) and in healthy full-term controls (46 infants born ≥ 37 weeks’ gestational age) were associated with later cognitive outcomes related to mathematics. Participants were enrolled in a prospective longitudinal cohort study in which an MRI was performed near term (40 weeks’ gestational age ± 2 weeks) to establish correlations predictive of cognitive impairment subsequently evident in neuropsychologic testing performed at 5 and 7 years’ corrected age.
Specifically, the authors were interested in looking at two automated MRI measures — a structural Jacobian map derived from deformation-based morphometry (DBM) and fractional anisotropy maps derived using diffusion tensor imaging (DTI). DBM is useful for identifying subtle differences in brain shape and regional volumetric differences, while DTI is sensitive in detecting the integrity of white matter tracts. To predict early mathematical ability, these investigators administered tests of working memory (Backward Digit Span Test) and early mathematics skills (Numbers Skills Scale at 5 years’ corrected age and Math Computation task at 7 years’ corrected age). For the statistical analysis, this research team used both a univariate analysis (general linear model) and a multivariate analysis (support vector regression) controlling for gestational age at birth, gestational age at time of MRI, and additional covariates related to prematurity (including small for gestational age, patent ductus arteriosus, bronchopulmonary dysplasia, postnatal steroids, confirmed sepsis, and other white matter injury based on review of the clinical MRI scans).
Based on the DBM Jacobian maps, the authors found that increased tissue volume in the left insula region was positively associated with higher scores on the Numbers Skills Scale at age 5 and increased tissue volume in the right putamen region was associated with higher scores on Math Computation at age 7. These findings were derived from a univariate analysis controlling for gestational age at birth and time of MRI as well as other clinical perinatal factors identified above. There was also a suggestion derived from the univariate analysis that increased volume in the left insula region was associated with increased working memory at age 7, but this did not reach statistical significance. For the DTI fractional anisotropy maps, there was a positive association with working memory at age 5 and Numbers Skills Scale at age 5 based on multivariate analysis controlling for gestational age at birth and time of MRI as well as other clinical perinatal factors identified above, but not for the univariate analysis. The authors then repeated these identical analyses in the control group and did not find significant associations for these structure/function relationships in the group of full-term children studied.
COMMENTARY
The cognitive and academic struggles experienced by many preterm children compared to their full-term peers can have a significant impact on their educability, subsequent employment, and professional well-being. This study showed that specific structural findings identified using automated morphometric and DTI analyses of neonatal MRI were predictive of future school age math performance. There are several limitations to these findings, including the low number of healthy controls in the comparison group, variability in imaging protocols over the course of the study, and an inability to control for all factors that undoubtedly contribute to childhood cognitive functioning in general, and math skills in particular. While the results of this study do not lend themselves to any immediate clinical application, they do highlight the potential for emerging neuroimaging analytic techniques to help characterize patterns of brain injury in premature children that can help predict subsequent cognitive and academic difficulties. Ultimately, the hope is that further research in this area will allow for routine screening that will lead to early identification of children at risk for cognitive deficits and permit for additional services and accommodations to be initiated when indicated.
Neonatal brain MRI can identify structural changes that predict future difficulties in school performance for children who are born preterm.
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