Title: Pain-Associated Stressor Exposure and Cortisol Values at 37 Postmenstrual Weeks for Premature Infants in Neonatal Intensive Care
Description: Background:Ongoing stress has costs in brain and body adaptations. Recurrent and prolonged stress taxes the adaptive capacity of the premature infant and has been postulated as a risk factor for the development of later disease. Cortisol appears to be an important mediator in the relationship between prolonged stress and subsequent disease and disability. Neonatal Intensive Care Unit (NICU) stress may give rise to early recognizable patterns of adrenal axis adaptation in prematurely born infants. These adaptations may underlie difficulties in learning and development for a population of children that already bears a high burden of disease. Premature infants who spend their first weeks of life in the NICU have been shown to have altered glucocorticoid values at approximately one year of age. It is hypothesized that adaptations of the adrenal axis may begin to emerge even earlier - during NICU hospitalization - and in relation to recurrent pain-associated procedural exposure or the prolonged stress of assisted ventilation.

Objective:The primary purpose of this research was to examine the relationship between random cortisol values at 37 postmenstrual weeks of age and pain-associated stressor exposure in prematurely born infants who received extended care in the NICU. Because random cortisol values in premature infants have been shown to be relatively dissociated from clinical conditions, this research also explored the relationship between values of the cortisol precursor, 17-hydroxyprogesterone (17-OHP), and pain-associated stressor exposure in prematurely born infants. Methods: A descriptive, cross-sectional design was used to examine relationships between two major types of pain-associated stressor exposures - number of recurrent skin-breaking procedures and hours of assisted ventilation - and random serum cortisol and 17-OHP values at 37 postmenstrual weeks of age. Subjects were 59 infants born at under 35 completed weeks of gestation, who were at least two weeks of age, and who had been cared for in in the NICU since birth.

Infants with intrauterine growth restriction, major anomalies, or exposure to postnatal steroids or surgery were excluded. Results:During this study, the 59 prematurely born infants were collectively exposed to over 3350 pain-associated procedures and over 17,000 hours of assisted ventilation. The greatest number of individual pain-associated exposures was 238, and no infant was exposed to less than 20 procedures (mean = 57). Over half of these exposures were in the first week after birth. There was a significant negative correlation (Spearman rank, one-tailed) between recurrent pain-associated stressor exposure in premature infants and their values of 17-OHP at 37 postmenstrual weeks of age (r= -0.232, p=0.039). A trend was also identified for differences in 17-OHP values between infants who had the highest and lowest recurrent pain-associated stressor exposure (U=68.5, p=0.068). No significant relationships were identified between cortisol values and any of the study variables. Due to multicollinearity, it was not possible to examine the independent effects of recurrent pain-associated stressor exposure, gestational age, chronological age or hours of ventilation on 17-OHP values.

One-tailed correlation analyses, however, failed to identify any significant relationships between the collinear variables or birthweight and 17-OHP values. Conclusions: Premature infants are exposed to a high number of recurrent skin-breaking procedures while receiving care in the NICU, especially during their first week of age. There is a statistically significant relationship between the incidence of these recurrent pain-associated procedures and an aspect of the adrenocorticoid profile at 37 postmenstrual weeks of age. Recurrent pain-associated stressor exposure may be a more important factor in explaining the variance of 17-OHP values at 37 postmenstrual weeks of age than birthweight, gestational age, chronological age or hours of assisted ventilation.