Punctate White Matter Abnormality in Moderate-to-Late Preterm Infants

Abstract

Objective: Moderate-to-late preterm (MLP) infants contribute to the greatest proportion of preterm children with neurodevelopmental impairments. White matter injury (WMI) is common and predicts adverse outcomes in very preterm (VP) infants. However, little is known about white matter abnormality (WMA) in MLP infants. We investigated the burden and distribution of WMA in MLP infants.

Methods: MLP infants were recruited from a randomized trial on neonatal nutrition and a prospective observational cohort in New Zealand, and underwent brain magnetic resonance imaging (MRI) soon after birth and at term-equivalent age (TEA). WMA was manually segmented using an established method. Total and regional WMA volumes and percentage of WMA to total cerebral volume were calculated. Probabilistic WMA maps were generated and compared with WMI in VP infants and term infants with congenital heart disease.

Results: Of 101 infants (32 females), 40 (39.6%) had WMA on at least 1 scan. In 37 infants with WMA who had both scans, WMA was less visible in 22 (59.5%) or undetectable in 7 (18.9%) infants with a mean reduction of 72.7 ± 207.5 mm³ in WMA volume from early-life to term. Infants with and without WMA had mostly comparable pregnancy and neonatal characteristics. Probabilistic maps demonstrated a characteristic WMA topology, with most lesions in posterior followed by central and anterior regions. Trigonal areas were vulnerable across neonatal populations.

Interpretation: WMA is much more common in MLP infants than previously reported and occurs in a characteristic topology. WMA may be missed on TEA MRI, and its relationship with outcomes in MLP infants warrants attention. ANN NEUROL 2025;98:329-340.

FIGURE 1

White matter abnormality in an moderate‐to‐late preterm infant at early‐life and term‐equivalent age. T1‐weighted images showing anterior and posterior multifocal punctate white matter abnormality (white arrows) in a baby born 32 + 6 weeks gestational age and scanned at early‐life MRI 1 (left): 34 + 1 weeks and term‐equivalent age MRI 2 (right): 39 + 6 weeks' post‐menstrual age. The white matter abnormality is less conspicuous at term‐equivalent age (right). MRI = magnetic resonance imaging.

FIGURE 2

White matter abnormality (WMA) volume and percentage changes from early‐life to term‐equivalent age in moderate‐to‐late preterm infants—in the subgroup of 37 infants with WMA who underwent MRI at both time points. Total WMA volume and percentage of total cerebral volume (TCV) (top row) and WMA volume in frontal, parietal, temporal, and occipital lobes from early‐life to term‐equivalent age (bottom row).

FIGURE 3

Probabilistic map of maximum white matter abnormality (WMA) identified in 40 moderate‐to‐late preterm (MLP) infants at early‐life or term‐equivalent age magnetic resonance imaging. The probabilistic WMA map of 40 MLP infants overlaid on the brain template displayed on (A) axial planes from superior to inferior, (B) coronal planes from anterior to posterior, and (C) sagittal planes from left to right. The color bar on the left indicates the color coding of the WMA summation where WMA occurs at homologous regions across the MLP infants.

FIGURE 4

Comparison between early‐life and term‐equivalent age (TEA) white matter abnormality (WMA) in moderate‐to‐late preterm (MLP) infants. The WMA identified in 36 MLP infants at early‐life and in 31 at TEA overlaid on the brain template displayed on axial (top), sagittal (middle), and coronal (bottom) planes at 3 locations. The color bar on the left indicates the color coding of the WMA summation where WMA occurs at homologous regions amongst the cohort.

FIGURE 5

Comparison of white matter abnormality (WMA) distribution in moderate‐to‐late preterm (MLP) infants with white matter injury (WMI) in very preterm (VP) infants and term congenital heart disease (CHD) infants. (A) Comparison of WMA identified in 40 MLP infants at early‐life or term‐ equivalent age with WMI in 68 VP infants from the Preterm Care (VP‐PTC) cohort (1st column) and in 58 VP infants from the Trajectories (VP‐Traj) cohort (2nd column) at early‐life, as well as with WMI in 86 term CHD infants (3rd column) on 3 axial planes of the brain template (top to bottom rows: superior to inferior direction). (B) Comparison of WMA/WMI on 4 sagittal planes of the brain template (top to bottom rows: left to right direction). Voxels in magenta: WMA identified only in MLP infants; voxels in blue: WMI identified only in VP‐PTC, VP‐Traj, or CHD infants; voxels in white: WMA/WMI that are common in MLP and any other cohort.