Procedural pain and brain development in premature newborns
Version of Record online: 28 FEB 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 71, Issue 3, pages 385–396, March 2012
How to Cite
Brummelte, S., Grunau, R. E., Chau, V., Poskitt, K. J., Brant, R., Vinall, J., Gover, A., Synnes, A. R. and Miller, S. P. (2012), Procedural pain and brain development in premature newborns. Ann Neurol., 71: 385–396. doi: 10.1002/ana.22267
- Issue online: 23 MAR 2012
- Version of Record online: 28 FEB 2012
- Manuscript Accepted: 4 NOV 2011
- Manuscript Revised: 24 OCT 2011
- Manuscript Received: 9 SEP 2011
- Canadian Institutes for Health Research. Grant Number: CIHR) MOP 79262 to S.P.M. and MOP 86489 to R.E.G.
Preterm infants are exposed to multiple painful procedures in the neonatal intensive care unit (NICU) during a period of rapid brain development. Our aim was to examine relationships between procedural pain in the NICU and early brain development in very preterm infants.
Infants born very preterm (N = 86; 24–32 weeks gestational age) were followed prospectively from birth, and studied with magnetic resonance imaging, 3-dimensional magnetic resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks). We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to choline ratios, average diffusivity, and white matter fractional anisotropy (FA) from up to 7 white and 4 subcortical gray matter regions of interest. Procedural pain was quantified as the number of skin-breaking events from birth to term or scan 2. Data were analyzed using generalized estimating equation modeling adjusting for clinical confounders such as illness severity, morphine exposure, brain injury, and surgery.
After comprehensively adjusting for multiple clinical factors, greater neonatal procedural pain was associated with reduced white matter FA (β = −0.0002, p = 0.028) and reduced subcortical gray matter NAA/choline (β = −0.0006, p = 0.004). Reduced FA was predicted by early pain (before scan 1), whereas lower NAA/choline was predicted by pain exposure throughout the neonatal course, suggesting a primary and early effect on subcortical structures with secondary white matter changes.
Early procedural pain in very preterm infants may contribute to impaired brain development. ANN NEUROL 2012;