Ventricular Volume in Infants Born Very Preterm: Relationship with Brain Maturation and Neurodevelopment at Age 4.5 Years

Abstract

To evaluate the relationship of quantitative ventricular volume with brain maturation and neurodevelopmental outcomes at age 4.5years in children born very preterm. T1-weighted imaging, diffusion tensor imaging, and magnetic resonance spectroscopy were performed shortly after birth (n=212) and at term-equivalent age (TEA) (n=194). Intraventricular hemorrhage (IVH) grade and white matter injury (WMI) volume were measured on early T1-weighted magnetic resonance imaging (MRI) scans. Total cerebral volume and ventricular volume were quantified using the Multiple Automatically Generated Templates-Brain pipeline. At age 4.5years, 178 children (84%) underwent cognitive and motor assessments. Multivariable linear regression was used to examine the relationships between ventricular volume and neurodevelopmental outcomes. Generalized estimating equations were used to account for repeated measures when analyzing neonatal MRI data. All models accounted for sex, postmenstrual age at scan, WMI volume, IVH grade, and total cerebral volume and were corrected for multiple comparisons. On early MRI, 97 infants had IVH (grade 1, n=22; grade 2, n=66; grade 3, n=9), and 68 had WMI (median, 44mm3; IQR, 21-296mm3). IQ at 4.5years was associated with MRI ventricular volume at the early (β=-0.64; P<.001) and TEA (β=-0.44, P<.001) time points. Motor outcomes were associated with ventricular volume at TEA (β=-0.84, P=.01). Greater ventricular volume independently predicted lower fractional anisotropy in corpus callosum (genu: β=-0.0008, P=.002; splenium: β=-0.003, P<.001) and optic radiations (β=-0.001, P=.004); ventricular volume did not predict the N-acetylaspartate/choline ratio. In children born very preterm, neonatal ventricular size was associated with 4.5-year neurodevelopmental outcomes. Our findings suggest that white matter maturation may be abnormal in the setting of enlarged ventricular size beyond that expected from concurrent brain injuries.