Neonatal intensive care unit stress is associated with brain development in preterm infants

Abstract

Objective: Although many perinatal factors have been linked to adverse neurodevelopmental outcomes in very premature infants, much of the variation in outcome remains unexplained. The impact on brain development of 1 potential factor, exposure to stressors in the neonatal intensive care unit, has not yet been studied in a systematic, prospective manner.

Methods: In this prospective cohort study of infants born at <30 weeks gestation, nurses were trained in recording procedures and cares. These recordings were used to derive Neonatal Infant Stressor Scale scores, which were employed to measure exposure to stressors. Magnetic resonance imaging (brain metrics, diffusion, and functional magnetic resonance imaging) and neurobehavioral examinations at term equivalent postmenstrual age were used to assess cerebral structure and function. Simple and partial correlations corrected for confounders, including immaturity and severity of illness, were used to explore these relations.

Results: Exposure to stressors was highly variable, both between infants and throughout a single infant's hospital course. Exposure to a greater number of stressors was associated with decreased frontal and parietal brain width, altered diffusion measures and functional connectivity in the temporal lobes, and abnormalities in motor behavior on neurobehavioral examination.

Interpretation: Exposure to stressors in the Neonatal Intensive Care Unit is associated with regional alterations in brain structure and function. Further research into interventions that may decrease or mitigate exposure to stressors in the neonatal intensive care unit is warranted.

Figure 1

Graphs showing average daily NISS score throughout admission to the NICU. The left pane depicts NISS score versus day of life for each infant for the first 28 days of life. Note that NISS score is higher and less variable between infants in the first days of life. The right pane depicts NISS score average daily NISS scores over the first and second 14 days of life and from 29 days. The black bar represents the median NISS score, the gray box the middle 50% of scores, and the whiskers the range of scores. Note that NISS score is greatest in the first 14 days and decreases thereafter.

Figure 2

Graphs showing relationships between average daily NISS score and (left pane) bifrontal diameter and (right pane) right temporal lobe relative anisotropy.

Figure 3

Mean functional connectivity correlation maps generated using the right temporal lobe seed in (A) term control infants (n=10) (B) low stress infants (n=10), (C) high stress infants (n=10). Illustrated quantity is Fisher z-transformed correlation coefficient (threshold value = 0.3). Note the average correlation map in the infants with high stress exposures does not demonstrate the interhemispheric correlation between the temporal lobes identified in low stress and term born control infants. The right side of image corresponds to the right side of brain. Age at scan, race, and gender were not significantly different between groups.