Cortisol, behavior, and heart rate reactivity to immunization pain at 4 months corrected age in infants born very preterm

Clin J Pain. 2010 Oct;26(8):698-704. doi: 10.1097/AJP.0b013e3181e5bb00.


Objective: Pain response may be altered in infants born very preterm owing to repeated exposure to procedures in the neonatal intensive care unit. Findings have been inconsistent in studies of behavioral and cardiac responses to brief pain in preterm versus full-term infants following neonatal intensive care unit discharge. To our knowledge, cortisol reactivity to pain has not been compared in preterm and full-term infants. We examined pain reactivity to immunization in preterm and full-term infants.

Method: Cortisol, facial behavior, and heart rate reactivity before, during, and after immunization were examined in infants born preterm at extremely low gestational age (ELGA 24 to 28 wk), very low gestational age (VLGA 29 to 32 wk), and full-term, at corrected age 4 months.

Results: In all groups, cortisol, behavior, and heart rate increased during immunizations. Cortisol concentrations were lower in preterm ELGA and VLGA boys, compared with full-term boys. In contrast, facial and heart rate responses to immunization did not differ between preterm and full-term infants.

Discussion: Although earlier reports found differences in pain processing in preterm infants earlier and later in development, the present findings indicate that pain responses, indexed by behavior and heart-rate, do not seem to differ in preterm compared with full-term infants at 4 months corrected age. Importantly, however, stress regulation seems altered in preterm male infants. As cortisol impacts development and functioning of the brain, altered stress regulation has important implications beyond pain systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Birth Weight / physiology
  • Face / physiopathology
  • Female
  • Gestational Age
  • Heart Rate / physiology*
  • Humans
  • Hydrocortisone / metabolism*
  • Immunization / adverse effects*
  • Infant
  • Infant Behavior*
  • Intensive Care Units, Neonatal
  • Male
  • Pain / etiology*
  • Pain / metabolism
  • Pain Measurement
  • Premature Birth* / immunology
  • Premature Birth* / physiopathology
  • Premature Birth* / psychology
  • Saliva / metabolism


  • Hydrocortisone