title: Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU.
abstract: Data from animal models indicate that neonatal stress or pain can permanently alter subsequent behavioral and/or physiological reactivity to stressors. However, cumulative effects of pain related to acute procedures in the neonatal intensive care unit (NICU) on later stress and/or pain reactivity has received limited attention. The objective of this study is to examine relationships between prior neonatal pain exposure (number of skin breaking procedures), and subsequent stress and pain reactivity in preterm infants in the NICU. Eighty-seven preterm infants were studied at 32 (+/-1 week) postconceptional age (PCA). Infants who received analgesia or sedation in the 72 h prior to each study, or any postnatal dexamethasone, were excluded. Outcomes were infant responses to two different stressors studied on separate days in a repeated measures randomized crossover design: (1) plasma cortisol to stress of a fixed series of nursing procedures; (2) behavioral (Neonatal Facial Coding System; NFCS) and cardiac reactivity to pain of blood collection. Among infants born <or=28 weeks gestational age (GA), but not 29-32 weeks GA, higher cumulative neonatal procedural pain exposure was related to lower cortisol response to stress and to lower facial (but not autonomic) reactivity to pain, at 32 weeks PCA, independent of early illness severity and morphine exposure since birth. Repeated neonatal procedural pain exposure among neurodevelopmentally immature preterm infants was associated with down-regulation of the hypothalamic-pituitary-adrenal axis, which was not counteracted with morphine. Differential effects of early pain on development of behavioral, physiologic and hormonal systems warrant further investigation.
authors.affiliation: Centre for Community Child Health Research, British Columbia Research Institute for Children's and Women's Health, Vancouver, BC, Canada Department of Pediatrics, University of British Columbia, Canada Department of Anatomy, Cell Biology and Physiology, University of British Columbia, Canada School of Rehabilitation Sciences, University of British Columbia, Canada Children's and Women's Health Centre of British Columbia, Vancouver, Canada.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Grunau
authors.forename: Liisa
authors.initials: L
authors.lastname: Holsti
authors.forename: David W
authors.initials: DW
authors.lastname: Haley
authors.forename: Tim
authors.initials: T
authors.lastname: Oberlander
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
authors.forename: Alfonso
authors.initials: A
authors.lastname: Solimano
authors.forename: Michael F
authors.initials: MF
authors.lastname: Whitfield
authors.forename: Colleen
authors.initials: C
authors.lastname: Fitzgerald
authors.forename: Wayne
authors.initials: W
authors.lastname: Yu
mesh_terms: D001794:Blood Pressure / Q000502:physiology; D018592:Cross-Over Studies; D004569:Electroencephalography / Q000379:methods; D005145:Face / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007223:Infant; D018730:Infant Behavior / Q000187:drug effects / Q000502:physiology*; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000502:physiology; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data*; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009294:Narcotics / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D011237:Predictive Value of Tests; D047928:Premature Birth / Q000503:physiopathology*; D011863:Radioimmunoassay / Q000379:methods; D013312:Stress, Physiological / Q000503:physiopathology
chemical_list: D009294:Narcotics; D009020:Morphine; D006854:Hydrocortisone