Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age

Abstract

Children born very prematurely (< or =32 weeks) often exhibit visual-perceptual difficulties at school-age, even in the absence of major neurological impairment. The alterations in functional brain activity that give rise to such problems, as well as the relationship between adverse neonatal experience and neurodevelopment, remain poorly understood. Repeated procedural pain-related stress during neonatal intensive care has been proposed to contribute to altered neurocognitive development in these children. Due to critical periods in the development of thalamocortical systems, the immature brain of infants born at extremely low gestational age (ELGA; < or =28 weeks) may have heightened vulnerability to neonatal pain. In a cohort of school-age children followed since birth we assessed relations between functional brain activity measured using magnetoencephalogragy (MEG), visual-perceptual abilities and cumulative neonatal pain. We demonstrated alterations in the spectral structure of spontaneous cortical oscillatory activity in ELGA children at school-age. Cumulative neonatal pain-related stress was associated with changes in background cortical rhythmicity in these children, and these alterations in spontaneous brain oscillations were negatively correlated with visual-perceptual abilities at school-age, and were not driven by potentially confounding neonatal variables. These findings provide the first evidence linking neonatal pain-related stress, the development of functional brain activity, and school-age cognitive outcome in these vulnerable children.

Keywords: Child development; Cognition; Cognitive outcome; Development; Magnetoencephalography; Neonatal pain; Neural oscillation; Pain; Perception; Prematurity; Preterm; Resting-state; Spontaneous brain activity; Visual perception.

Fig. 1

Group differences in the spectral structure of spontaneous MEG oscillations. The dot represents an outlier.

Fig. 2

Correlations between MEG spectral structure and visual-perceptual abilities, indexed by (a) the perceptual reasoning index of the WISC-IV; and (b) the visual perception subscore of the Beery VMI.

Fig. 3

Interaction effects are illustrated by showing the regression slopes for the ELGA and VLGA groups separately. Associations between neonatal pain and spontaneous MEG oscillations for the ELGA and VLGA groups, adjusted for medical confounders (number of surgeries, cumulative morphine, illness severity, and number of days on mechanical ventilation) are displayed as the plot of the residuals computed from regression analysis.