Hypothalamic-Pituitary-Adrenal Axis Function in Very Low Birth Weight Infants Treated With Dexamethasone

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Abstract
The effect of dexamethasone therapy on hypothalamic-pituitary-adrenal axis function was prospectively investigated in very low birth weight infants with bronchopulmonary dysplasia. Ten infants (mean ± SD birth weight 825 ± 265 g, gestation 25.8 ± 1.9 weeks, postnatal age 33.1 ± 17.7 days) initially received intravenous dexamethasone, 0.5 mg/kg per day for 3 days, and then were weaned over a period of 45 ± 19.0 days to a replacement dose, followed by a metyrapone test. Morning plasma cortisol and 11-deoxycortisol levels were measured before and after an oral metyrapone dose given at midnight. Five infants (group A: birth weight 876 ± 313 g, gestation 26.2 ± 1.3 weeks, age of entry 31.8 ± 22.8 days) had normal metyrapone test results, and five infants (group B: 778 ± 234 g, 25.4 ± 2.5 weeks, 34.4 ± 13.4 days) had suppressed test results. Group A infants, in comparison with group B infants, had higher basal cortisol plasma levels (14.52 ± 12.53 and 3.00 ± 1.38 µg/dL, P = .047), higher postmetyrapone 11-deoxycortisol plasma levels (3.11 ± 3.93 and 0.55 ± 0.51 µg/dL, P = .028), larger differences between basal and postmetyrapone cortisol levels (7.10 ± 4.67 and 2.12 ± 1.31 µg/dL, P = .047), and larger differences between basal and postmetyrapone 11-deoxycortisol levels (2.99 ± 3.93 and 0.29 ± 0.25 µg/dL, P = .009). The hypothalamic-pituitary-adrenal axis function in group B infants eventually returned to normal when they continued to receive low-dose dexamethasone therapy after a period of 36.8 ± 16.6 days. The results suggest that dexamethasone therapy given for several weeks or more may be associated with prolonged suppression of hypothalamic-pituitary-adrenal axis function in a substantial number of very low birth weight infants with bronchopulmonary dysplasia. Evaluation of hypothalamic-pituitary-adrenal axis function before discontinuation of dexamethasone therapy is necessary to ensure proper adrenal secretory response.