Early activation of the hypothalamic-pituitary-adrenal-axis in very-low-birth-weight infants with small thymus at birth

Background. An acute thymic involution in human fetuses and newborns has been described in very-low-birth-weight (VLBW) infants with histological chorioamnionitis. However, the mechanisms of thymic involution remain to be clarified. Here, we tested the hypothesis that an activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in VLBW infants with acute thymic involution at birth. Methods. A total of 180 randomly selected VLBW newborns (28.8 +/- 3.15wk gestation; 1093 +/- 305 g) entered the study. Thymic size was measured on standard chest radiographs at birth, and expressed as the ratio between the transverse diameter of the cardiothymic image at the level of the carina (CT) and that of the thorax (T). CT/T<0.28 was considered to indicate a small thymic size. Plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations were determined on days 1 (d-1) and 7 (d-7), and at 1 month (mo-1). Results. A total of 66 (36.7%) newborns had CT/T<0.28. Infants with small thymus had significantly increased cortisol on d-1 (similar to 5.2-folds) [median: 18.95 (95% CI: 11.20-39.4) mu g/dl vs. 3.66 (1.94-6.82) mu g/dl, p 0.0001)] and d-7(similar to 1.7-folds) [12.0 (4.39-22.97) mu g/dl vs. 7.8 (3.63-12.8) mu g/dl, p=0.0384)], as compared with those with normal thymic size, together with higher adrenocorticotropic hormone (ACTH) concentrations on d-1 (similar to 1.9-folds) [28 (15.6-61.07) pg/ml vs. 14.9 (9.0-23.42) pg/ml, p=0.0005)], while no significant differences for cortisol at mo-1 or ACTH concentrations on d-7 and mo-1 were evidenced (p>0.50). From a multivariate logistic regression analysis, a small thymus at birth was a significant independent predictor of plasma cortisol concentrations in the top-quartile (OR=14.4; 95% CI: 6.079-34.11), and plasma ACTH concentrations in the top-quartile (OR=4.40 (95% CI: 1.99-9.74) on d-1 (results adjusted for variables significant at univariate analysis). Conclusions. Our data indicated the presence of a previously unrecognized, early activation of the HPA axis in VLBW newborns with a small thymus at birth.