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 weeks) 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 ≤ 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.

Cortisol, contingency learning, and memory in preterm and full-term infants

“…The etiology of these learning difficulties is unknown. Recently, we found that stress and pain during the neonatal period are associated with alterations in HPA activation in subsequent challenges (Grunau et al, , 2005. Together with these data, our current findings begin to elucidate the complex linkages between cortisol secretion, learning, and memory in preterm infants.…”

“…Preterm infants were recruited through the Neonatal Intensive Care Unit (NICU) at the Children's and Women's Health Centre of British Columbia, Vancouver as part of an ongoing program of studies on the effects of premature birth and early pain exposure on regulatory processes and development (Grunau et al, , 2005Haley et al, 2004). As part of this larger study, chart reviews from birth to term were carried out (see Table 1).…”

Initial validation of the Behavioral Indicators of Infant Pain (BIIP)

“…Gestational age at birth was chosen as the grouping variable because birth weight, illness severity, gestational age and pain exposure are variables which are highly inter-correlated (e.g. Grunau et al, 2005). All analyses remained the same with the exception of the construct validity analysis; to determine whether there were differences between BIIP scores between the two groups across the three phases (Baseline, Lance/squeeze, Recovery), repeated measures analysis of variance with gestational age group as a between subjects factor was completed.…”

The Effects of Early Pain Experience in Neonates on Pain Responses in Infancy and Childhood

“…A recent three-group study investigated long-term changes in cutaneous abdominal sensitivity in infants with pathologic abdominal disease and presumed abdominal visceral pain.l 29 1 Group 1 comprised newly born preterm and full-term neonat·es [30][31][32][33][34][35][36][37][38][39][40][41] weeks' post-conceptional age (n = 25); group 2 comprised infants with unilateral hydronephrosis (UH) 2-95 weeks' post-conceptional age (n = 30); and group 3 comprised healthy control infants 42-95 weeks' post-conceptional age (n = 52). Using nylon von Frey hairs (monoti laments of varying diameters designed to apply fixed forces to the skin).…”