Early Procedural Pain Is Associated with Regionally-Specific Alterations in Thalamic Development in Preterm Neonates

• DOI: 10.1523/jneurosci.0867-17.2017
• Publication Date: 2017-12-18T18:45:23Z
• Authors: Emma G. Duerden; Ruth E. Grunau; Ting Guo; Justin Foong; Alexander Pearson; Stephanie Au-Young; Raphael Lavoie; M. Mallar Chakrav...; Vann Chau; Anne Synnes; Steven P. Miller
• Keywords: Male; Procedural; 610; Pain; Extremely Premature; Pain, Procedural; Education; 618; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Developmental Neuroscience; Thalamus; Psychology; Humans; Prospective Studies; Child; Preschool; Systems Biology; Neurosciences; Infant, Newborn; Infant; Newborn; Diffusion Tensor Imaging; Neurodevelopmental Disorders; Child, Preschool; Infant, Extremely Premature; Female

Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain development. However, date the link between and development has limited temporal anatomic specificity. We hypothesized early exposure painful stimuli during a period rapid development, before modulatory systems reach maturity, will predict pronounced changes thalamic thereby cognitive motor function. In prospective cohort study, 155 very (82 males, 73 females) born 24–32 weeks' gestation underwent two MRIs at median postmenstrual ages 32 40 weeks included structural, metabolic, diffusion imaging. Detailed day-by-day clinical data were collected. Cognitive abilities assessed 3 years, corrected age. The association (skin breaks, birth–Scan 1) late Scans 1–2) with volumes N -acetylaspartate (NAA)/choline (Cho), fractional anisotropy white-matter pathways was assessed. Early associated slower macrostructural growth, most extremely premature neonates. Deformation-based morphometry analyses confirmed pain-related volume losses localized somatosensory regions. decreased NAA/Cho microstructural thalamocortical pathways. Thalamic growth turn related outcomes. observed regionally-specific lateral thalamus more pain. Findings suggest sensitive leading lasting somatosensory-system SIGNIFICANCE STATEMENT may disrupt regions involved processing, poor functional demonstrate is loss territory accompanied by disruptions metabolic pathway maturation, particularly outcome years provide evidence for developmentally whereby subcortical structures young be vulnerable Furthermore, results play key role underlying neurodevelopmental outcomes these high-risk