title: Procedural pain and brain development in premature newborns.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Early procedural pain in very preterm infants may contribute to impaired brain development.
authors.affiliation: Developmental Neurosciences and Child Health, Child and Family Research Institute, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brummelte
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Grunau
authors.forename: Vann
authors.initials: V
authors.lastname: Chau
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Poskitt
authors.forename: Rollin
authors.initials: R
authors.lastname: Brant
authors.forename: Jillian
authors.initials: J
authors.lastname: Vinall
authors.forename: Ayala
authors.initials: A
authors.lastname: Gover
authors.forename: Anne R
authors.initials: AR
authors.lastname: Synnes
authors.forename: Steven P
authors.initials: SP
authors.lastname: Miller
mesh_terms: D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development* / Q000378:metabolism; D007363:Intensive Care Units, Neonatal; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*; D010146:Pain / Q000378:metabolism / Q000473:pathology*; D010147:Pain Measurement / Q000379:methods; D011446:Prospective Studies