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Cry presence and amplitude do not reflect cortical processing of painful stimuli in newborns with distinct responses to touch or cold
  1. Nathalie L Maitre1,2,
  2. Ann R Stark3,
  3. Carrie C McCoy Menser4,
  4. Olena D Chorna1,
  5. Daniel J France4,5,
  6. Alexandra F Key2,6,
  7. Ken Wilkens7,
  8. Melissa Moore-Clingenpeel8,9,
  9. Don M Wilkes10,
  10. Stephen Bruehl4
  1. 1 Center for Perinatal Research, Nationwide Children’s Hospital, Columbus, Ohio, USA
  2. 2 Department of Hearing and Speech Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  3. 3 Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Texas, USA
  4. 4 Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  5. 5 Center for Research & Innovation in Systems Safety, Vanderbilt University, Nashville, Tennessee, USA
  6. 6 Vanderbilt Kennedy Center, Vanderbilt University, Nashville, Tennessee, USA
  7. 7 Institute of Imaging Science Vanderbilt University, Vanderbilt University, Nashville, Tennessee, USA
  8. 8 Biostatistics Core at The Research Institute, Nationwide Children’s Hospital, Columbus, Ohio, USA
  9. 9 Division of Pediatric Critical Care Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA
  10. 10 Electrical Engineering & Computer Science, Vanderbilt University, Nashville, Tennessee, USA
  1. Correspondence to Dr Nathalie L Maitre, Address Correspondence to: Dr Nathalie L Maitre, 700 Children’s Drive, WB6225, Columbus, OH 43205, USA; nathalie.maitre{at}nationwidechildrens.org

Abstract

Objective Newborns requiring hospitalisation frequently undergo painful procedures. Prevention of pain in infants is of prime concern because of adverse associations with physiological and neurological development. However, pain mitigation is currently guided by behavioural observation assessments that have not been validated against direct evidence of pain processing in the brain. The aim of this study was to determine whether cry presence or amplitude is a valid indicator of pain processing in newborns.

Design Prospective observational cohort.

Setting Newborn nursery.

Patients Healthy infants born at >37 weeks and <42 weeks gestation.

Interventions We prospectively studied newborn cortical responses to light touch, cold and heel stick, and the amplitude of associated infant vocalisations using our previously published paradigms of time-locked electroencephalogram (EEG) with simultaneous audio recordings.

Results Latencies of cortical peak responses to each of the three stimuli type were significantly different from each other. Of 54 infants, 13 (24%), 19 (35%) and 35 (65%) had cries in response to light touch, cold and heel stick, respectively. Cry in response to non-painful stimuli did not predict cry in response to heel stick. All infants with EEG data had measurable pain responses to heel stick, whether they cried or not. There was no association between presence or amplitude of cries and cortical nociceptive amplitudes.

Conclusions In newborns with distinct brain responses to light touch, cold and pain, cry presence or amplitude characteristics do not provide adequate behavioural markers of pain signalling in the brain. New bedside assessments of newborn pain may need to be developed using brain-based methodologies as benchmarks in order to provide optimal pain mitigation.

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Footnotes

  • Acknowledgements The authors thank Dorita Jones and Ellyn Hamm for assistance with ERP data acquisition and processing.

  • Contributors NLM: designed the study in its final form, participated in data collection, carried out preliminary analyses, wrote, reviewed and revised all drafts the manuscript and approved the final manuscript as submitted. ARS: contributed to study interpretation, reviewed and revised all drafts of the manuscript and approved the final manuscript as submitted. CCMM: participated in the study design and in data collection, drafted the initial manuscript, and approved the final manuscript as submitted. ODC: participated in data collection, reviewed and revised all drafts of the manuscript and approved the final manuscript as submitted. DJF: designed the study in its final form, carried out preliminary analyses, reviewed and revised all drafts of the manuscript and approved the final manuscript as submitted. AFK: participated in data collection, reviewed and revised all drafts of the manuscript and approved the final manuscript as submitted. KW: designed the touch apparatus, carried out preliminary analyses, reviewed and revised all drafts of the manuscript and approved the final manuscript as submitted. MMC: designed and performed the final statistical analyses and approved the final manuscript as submitted. DMW: carried out preliminary analyses, reviewed and revised all drafts of the manuscript and approved the final manuscript as submitted. SB: designed the study in its final form, carried out preliminary analyses, reviewed and revised all drafts of the manuscript and approved the final manuscript as submitted.

  • Funding This work was supported by the Hobbs Discovery Grant from the Vanderbilt Kennedy Center, NICHD grants [P30HD015052], [U54HD083211], [K23HD074736(01A1], [1R01HD081120(01A1], NCATS/NIH [UL1 TR000445].

  • Competing interests None declared.

  • Ethics approval Vanderbilt University Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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