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

Min Sheng; Ting Guo; Connor Mabbott; Vann Chau; Anne Synnes; Linda S de Vries; Ruth E Grunau; Steven P Miller

doi:10.1016/j.jpeds.2022.05.003

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

J Pediatr. 2022 Sep:248:51-58.e2. doi: 10.1016/j.jpeds.2022.05.003. Epub 2022 May 11.

Authors

Min Sheng¹, Ting Guo¹, Connor Mabbott¹, Vann Chau¹, Anne Synnes², Linda S de Vries³, Ruth E Grunau², Steven P Miller⁴

Affiliations

¹ Department of Paediatrics, University of Toronto and the Hospital for Sick Children, Toronto, Ontario, Canada.
² Department of Pediatrics, University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
³ Department of Neonatology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁴ Department of Paediatrics, University of Toronto and the Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada. Electronic address: steven.miller@cw.bc.ca.

PMID: 35561806
DOI: 10.1016/j.jpeds.2022.05.003

Abstract

Objective: To evaluate the relationship of quantitative ventricular volume with brain maturation and neurodevelopmental outcomes at age 4.5 years in children born very preterm.

Study design: 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 4.5 years, 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.

Results: On early MRI, 97 infants had IVH (grade 1, n = 22; grade 2, n = 66; grade 3, n = 9), and 68 had WMI (median, 44 mm³; IQR, 21-296 mm³). IQ at 4.5 years 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.

Conclusions: 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.

Keywords: fractional anisotropy; magnetic resonance imaging; outcomes; ventricular dilatation; very preterm birth.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / pathology
Brain Injuries* / pathology
Cerebral Hemorrhage / pathology
Child
Child, Preschool
Choline
Diffusion Tensor Imaging
Gestational Age
Humans
Infant
Infant, Extremely Premature
Infant, Newborn
Magnetic Resonance Imaging / methods
White Matter*

Substances

Choline

Abstract

Publication types

MeSH terms

Substances

Grants and funding