Do Cortisol Concentrations Predict Short-Term Outcomes in Extremely Low Birth Weight Infants?

Abstract

OBJECTIVE Relative adrenal insufficiency in extremely low birth weight infants may contribute to significant morbidity and death. Our objective was to evaluate the relationship between cortisol concentrations and short-term outcomes. METHODS Cortisol concentrations were obtained for 350 intubated, extremely low birth weight infants at postnatal age of 12 to 48 hours and at day 5 to 7, as part of a multicenter, randomized trial of hydrocortisone treatment for prophylaxis of relative adrenal insufficiency. Death and short-term morbidity were monitored prospectively. Cortisol levels at each time point were divided into quartiles. The incidence rates of outcomes were determined for each quartile and for infants with cortisol values of <10th percentile or >90th percentile. RESULTS Median cortisol values were 16.0 μg/dL at baseline and 13.1 μg/dL on day 5 to 7 in the placebo group. Outcomes did not differ in each quartile between treatment and placebo groups. Low cortisol values at baseline or day 5 to 7 were not associated with increased morbidity or mortality rates and were not predictive of open-label hydrocortisone use. In fact, vasopressor use was lower for infants with lower cortisol values at baseline. Severe intraventricular hemorrhage was more frequent in infants with cortisol levels in the upper quartile at baseline, and values of >90th percentile were significantly associated with higher rates of death, severe intraventricular hemorrhage, periventricular leukomalacia, gastrointestinal perforation, and severe retinopathy of prematurity. CONCLUSIONS Low cortisol concentrations were not predictive of adverse short-term outcomes, but high cortisol concentrations were associated with severe intraventricular hemorrhage, and extremely elevated values were associated with morbidity and death. Low cortisol concentrations alone at these 2 time points did not identify the infants at highest risk for adverse outcomes. In contrast, high cortisol values were associated with increased morbidity and mortality rates.

Cardiovascular instability after patent ductus arteriosus ligation in preterm infants: the role of hydrocortisone

“…Identifying infants with relative adrenal insufficiency is difficult; measuring cortisol levels may be useful, however, studies have shown that low cortisol levels are not helpful in defining a population who would benefit from HC therapy. 10,15,16 In our case, information regarding cortisol levels before treatment was not available. Interestingly, those infants who were not pretreated with prophylactic stress HC but subsequently required HC for pressor-resistant hypotension were not clinically different from others in the non-treated group, indicating the challenge of identifying these infants prospectively.…”

“…A subset of infants may have an inadequate cortisol response during acute illness that results in changes in vasomotor tone, hypotension and increased dependence on vasopressor support. 13,15 We postulate that relative adrenal insufficiency may have a role in the postoperative decompensation of some premature infants and, providing HC before the stressful event may aid the infants in producing an appropriate response and possibly prevent poor long-term outcomes. Identifying infants with relative adrenal insufficiency is difficult; measuring cortisol levels may be useful, however, studies have shown that low cortisol levels are not helpful in defining a population who would benefit from HC therapy.…”

Stress and severity of illness in very low birth weight infants: what are we measuring?

“…[11][12][13][14] Despite this, prophylactic supplementation with hydrocortisone in high-risk infants did not reduce the incidence of bronchopulmonary dysplasia. 15 Low cortisol concentrations at day 7 of life, rather than day 1, have been associated with low blood pressure and the need for vasopressor agents, 8 although this was not shown by others, 7 and prophylactic treatment with hydrocortisone did not impact the need for vasopressor therapy. 15 The clinical implication of a low cortisol value, at either day 1 or day 7 of life, remains unclear.…”

“…This is consistent with other studies that have not found an association between early cortisol concentrations and blood pressure or the need for inotropic support. 7,8 The interpretation of cortisol values in VLBW infants has remained a challenge. In utero, cortisol concentrations are very low and can remain low in healthy preterm infants without demonstrating evidence of relative adrenal insufficiency.…”

“…16 There is a growing concern regarding the clinical implication of high cortisol values in the VLBW population. 1,7,15,16 The subset of critically ill infants who show an exaggerated response to stress has been associated with increased adverse outcomes, specifically spontaneous gastrointestinal perforations, 15 intraventricular hemorrhage, periventricular leukomalacia and death. 16 These adverse outcomes are not associated with the use of hydrocortisone, rather with the innate response of these infants.…”