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Brain Volumes at Term-Equivalent Age in Preterm Infants: Imaging Biomarkers for Neurodevelopmental Outcome through
Kristin Keunen1, Ivana Išgum2, Britt J M van Kooij3
1Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Brain volumes in preterm infants can predict neurodevelopmental outcomes. Larger ventricular and cortical gray matter volumes were linked to poorer outcomes, while unmyelinated white matter and cerebellar volumes showed positive associations.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatrics
Background:
- Preterm birth is associated with an increased risk of neurodevelopmental deficits.
- Early identification of biomarkers is crucial for timely intervention in preterm infants.
Purpose of the Study:
- To investigate the association between brain tissue volumes measured by MRI at term-equivalent age and neurodevelopmental outcomes in preterm infants up to early school age.
- To identify potential brain volume biomarkers for predicting neurodevelopmental trajectories in this population.
Main Methods:
- Prospective study of 112 preterm infants (mean gestational age 28.6 weeks).
- Magnetic resonance imaging (MRI) at mean corrected age 41.6 weeks with automated segmentation of 6 tissue types.
- Neurodevelopmental assessments at 24 months, 3.5 years, and 5.5 years using standardized tests (Bayley Scales, Griffiths Scales, Movement Assessment Battery, WPPSI-III).
- Statistical analysis adjusted for intracranial volume, maternal education, and severe brain lesions.
Main Results:
- Increased ventricular volumes correlated with poorer neurodevelopmental outcomes at 24 months and 3.5 years, and slower processing speed at 5.5 years.
- Larger unmyelinated white matter (UWM) volume was associated with better motor outcomes at 24 months and faster processing speed at 5.5 years.
- Greater cortical gray matter (CGM) volume showed negative associations with motor and cognitive scores at 24 months and developmental quotient at 3.5 years.
- Increased cerebellar volume was positively related to cognitive function at both 24 months and 3.5 years.
Conclusions:
- Brain volumes, specifically of ventricles, UWM, CGM, and cerebellum, may serve as valuable biomarkers for predicting neurodevelopmental outcomes in preterm infants.
- The observed association between larger CGM volumes and adverse neurodevelopment suggests potential disturbances in neuronal migration, warranting further investigation.
Objective:
To evaluate the relationship between brain volumes at term and neurodevelopmental outcome through early school age in preterm infants.
Study Design:
One hundred twelve preterm infants (born mean gestational age 28.6 ± 1.7 weeks) were studied prospectively with magnetic resonance imaging (imaged at mean 41.6 ± 1.0 weeks). T2- and T1-weighted images were automatically segmented, and volumes of 6 tissue types were related to neurodevelopmental outcome assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (cognitive, fine, and gross motor scores) at 24 months corrected age (n = 112), Griffiths Mental Development Scales (developmental quotient) at age 3.5 years (n = 98), Movement Assessment Battery for Children, Second Edition (n = 85), and Wechsler Preschool and Primary Scale of Intelligence, Third Edition at age 5.5 years (n = 44). Corrections were made for intracranial volume, maternal education, and severe brain lesions.
Results:
Ventricular volumes were negatively related to neurodevelopmental outcome at age 24 months and 3.5 years, as well as processing speed at age 5.5 years. Unmyelinated white matter (UWM) volume was positively associated with motor outcome at 24 months and with processing speed at age 5.5 years. Cortical gray matter (CGM) volume demonstrated a negative association with motor performance and cognition at 24 months and with developmental quotient at age 3.5 years. Cerebellar volume was positively related to cognition at these time points. Adjustment for brain lesions attenuated the relations between cerebellar and CGM volumes and cognition.
Conclusions:
Brain volumes of ventricles, UWM, CGM, and cerebellum may serve as biomarkers for neurodevelopmental outcome in preterm infants. The relationship between larger CGM volumes and adverse neurodevelopment may reflect disturbances in neuronal and/or axonal migration at the UWM-CGM boundary and warrants further investigation.
