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Cortisol, Behavior, and Heart Rate Reactivity to Immunization Pain at 4 Months Corrected Age in Infants Born Very Preterm

Grunau, Ruth E. PhD* †; Tu, Mai Thanh PhD; Whitfield, Michael F. MD (FRCPC)* †; Oberlander, Tim F. MD (FRCPC)* †; Weinberg, Joanne PhD† ‡; Yu, Wayne BSc; Thiessen, Paul MD (FRCPC)*; Gosse, Gisela RN; Scheifele, David MD (CRPC)* †

doi: 10.1097/AJP.0b013e3181e5bb00
Original Articles

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.

*Department of Pediatrics, University of British Columbia

Child and Family Research Institute

Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver BC, Canada.

Supported by grants to REG from the Canadian Institutes of Health Research (CIHR; MOP42469), to REG from the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD39783), and to JW from the Human Early Learning Partnership (HELP 20R41341). REG was supported by a Distinguished Scholar Award from the Child and Family Research Institute, and Senior Scholar Awards from HELP and the Michael Smith Foundation for Health Research. MTT was supported by the CIHR Pain in Child Health Strategic Training Program and the Fonds de la Recherche en Santé du Québec

Reprints: Ruth E. Grunau, PhD, Developmental Neurosciences & Child Health, F605B—4480 Oak Street, Vancouver, British Columbia, V6H 3V4, Canada (e-mail:

Received for publication November 15, 2009; revised April 12, 2010; accepted April 22, 2010

© 2010 Lippincott Williams & Wilkins, Inc.