17Beta-estradiol and progesterone supplementation in extremely low-birth-weight infants.

During pregnancy, 17beta-estradiol (E2) and progesterone (P) plasma concentrations increase up to 100-fold. The fetus is exposed to these increasing amounts of E2 and P. Within 1 d after delivery, E2 and P concentrations fall to nonpregnancy concentrations in the mother and the infant. Extremely premature infants are cut off from the placental supply of E2 and P at a very early developmental stage, and therefore they suffer from this deprivation for a longer period than infants born at term. Nothing is known about the consequences of this deprivation. The purpose of this study was to investigate how intrauterine concentrations of E2 and P could be maintained after birth. In 13 infants with a median gestational age of 26.4 wk (24.1-28.7), a phospholipid-stabilized soybean oil emulsion available for parenteral nutrition that contains different amounts of E2 and P was continuously administered, starting within the first postnatal hours. The supplementation was continued as long as venous access was indicated but not longer than 6 wk (median 20 d, 12-44). To maintain intrauterine plasma concentrations of 2000-6000 pg/mL E2 and 300-600 ng/mL P, 2.30 mg x kg(-1) x d(-1) E2 (1.13-3.42 mg x kg(-1) x d(-1)) and 21.20 mg x kg(-1) x d(-1) P (11.23-27.36 mg x kg(-1) x d(-1)) were needed. We conclude that supplementation of E2 and P to maintain intrauterine concentrations in extremely premature infants is possible intravenously. The infants in this study are enrolled in a randomized, controlled pilot study to evaluate the potential benefits of E2 and P supplementation.

Assessment of hypothalamic-pituitary-adrenocortical axis function in dexamethasone treated very low birth weight infants by a single dose metyrapone test and gas chromatographic mass spectrometric determination of urinary steroids.

In order to assess hypothalamic-pituitary-adrenocortical axis function, we conducted low and single oral dose metyrapone tests (35 mg/kg) in dexamethasone treated very low birth weight infants with bronchopulmonary dysplasia (n = 12). The responses to metyrapone of tetrahydro-11-deoxycortisol (THS) and cortisol metabolites were analyzed by gas chromatography and mass spectrometry in 24-h urinary specimens. For comparative reasons, morning plasma 11-deoxy-cortisol and cortisol were measured by radioimmunoassay before and after metyrapone. No side effects of metyrapone were observed in our patients. In 5 of 12 patients, no urinary THS could be stimulated after metyrapone and most of the other patients had small increases in urinary THS. These findings suggest suppressed or strongly impaired hypothalamic-pituitary-adrenocortical axis function in most patients. While the concentrations of plasma 11-deoxycortisol showed little variation, those of plasma cortisol were grossly different from the respective urinary values. We recommend steroid analysis in 24-h urinary specimens by gas chromatography and mass spectrometry, because urinary steroids provide more information and the highly specific analytical technique is independent of phenomena such as cross reactivity or matrix effects. The low and single oral dose metyrapone test in combination with urinary steroid analysis by gas chromatography and mass spectrometry therefore provides a noninvasive, convenient and safe means of evaluating the integrity of the hypothalamic-pituitary-adrenocortical axis in very low birth weight infants.