cortodoxone and Birth-Weight

Relative adrenocortical insufficiency is often seen in sick premature newborns. As the human fetal adrenal cortex does not express the 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme before about 23 weeks of gestation, we hypothesized that this enzymatic step may be rate limiting in cortisol synthesis in premature infants of less than 28 weeks postmenstrual age at birth.. We measured cord, first day (D0) and median fourth day (D4) serum 17-OH-pregnenolone (17-OHPreg), 17-OH-progesterone (17-OHProg), 11-deoxycortisol, cortisol (F) and dehydroepiandrosterone sulphate concentrations and calculated the substrate/product ratios in 67 infants with gestational age 23.6-33.1 weeks.. The mean 17-OHPreg/17-OHProg ratio as a marker of 3β-HSD activity did not differ between the gestational age groups (gestational age <28 vs. ≥28 weeks: 0.40 vs. 0.48, p = 0.52 for cord, 3.1 vs. 2.4, p = 0.25 for D0, and 1.6 vs. 1.9, p = 0.62 for D4). In addition, the 17-OHPreg/17-OHProg ratio did not differ between the infants in the lowest F tertile compared to those in the highest F tertile group, and the serum 17-OHPreg and 17-OHProg concentrations were parallel with the respective F concentrations.. We did not find evidence of significant immaturity in adrenal 3β-HSD activity in preterm infants between 24 and 28 weeks of gestation.

Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; 3-Hydroxysteroid Dehydrogenases; Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adult; Apgar Score; Birth Weight; Chorioamnionitis; Cohort Studies; Cortodoxone; Dehydroepiandrosterone Sulfate; Female; Fetal Blood; Gestational Age; Humans; Hydrocortisone; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Pre-Eclampsia; Pregnancy; Prospective Studies

Reduced size at birth in humans has been associated with altered function of the hypothalamic-pituitary-adrenal (HPA) axis in childhood and adult life. Experimentally, maternal undernutrition has also been associated with altered fetal HPA function. However, the relationship between birth size, fetal nutrition, and adult pathophysiology is not clear. We recently have reported that glucose tolerance, blood pressure, and IGF-I levels in adult sheep were more closely associated with birth weight than with nutritional insult in late gestation or with current weight. Here, we report adult HPA function in the same group of animals. Pregnant ewes were severely undernourished for 10 d (UN10) or 20 d (UN20) from 105 d gestation (term, 146 d), or were ad libitum-fed controls. At 30 months, female offspring were subjected to an insulin tolerance test and a CRH plus arginine vasopressin (AVP) challenge. UN20 lambs were lighter at birth, but there were no significant differences in weight at 30 months. Adult UN10 ewes had an increased ACTH response to both CRH+AVP challenge and insulin tolerance test, but no differences in cortisol response. UN10 ewes also demonstrated elevated 11-deoxycortisol concentrations, but lower progesterone concentrations, in response to CRH+AVP challenge. In contrast, the responses of UN20 ewes to these challenges were not different from ad libitum controls. Protein levels of P450(c17) and P450(11beta1) were not significantly different among groups. We conclude that brief maternal undernutrition for 10 d, but not 20 d, in late gestation alters HPA function in adult offspring. In contrast to our previous findings, these HPA effects are independent of birth weight and current weight, suggesting that different mechanisms may be involved in programming different physiological axes.

Topics: Adrenocorticotropic Hormone; Age Factors; Androstenedione; Animals; Animals, Newborn; Birth Weight; Cortodoxone; Female; Gestational Age; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Placental Insufficiency; Pregnancy; Progesterone; Sheep

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 micrograms/dL, P = .047), higher postmetyrapone 11-deoxycortisol plasma levels (3.11 +/- 3.93 and 0.55 +/- 0.51 micrograms/dL, P = .028), larger differences between basal and postmetyrapone cortisol levels (7.10 +/- 4.67 and 2.12 +/- 1.31 micrograms/dL, P = .047), and larger differences between basal and postmetyrapone 11-deoxycortisol levels (2.99 +/- 3.93 and 0.29 +/- 0.25 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Birth Weight; Bronchopulmonary Dysplasia; Cortodoxone; Dexamethasone; Drug Administration Schedule; Female; Gestational Age; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant; Infant, Low Birth Weight; Infant, Newborn; Intensive Care Units, Neonatal; Male; Metyrapone; Pituitary-Adrenal System; Prospective Studies; Respiration

To evaluate serum adrenal steroid concentrations in preterm infants, 17-hydroxyprogesterone (17-OHP), 17-hydroxypregnenolone, 11-deoxycortisol, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione, 18-hydroxycorticosterone, and aldosterone values were determined in 9 sick and 13 healthy premature infants. Serum steroid concentrations were compared to previously reported data from healthy full-term infants. 17-OHP, 11-deoxycortisol, and aldosterone values were higher in sick preterm infants than in healthy preterm infants. Compared to healthy full-term infants, the premature infants-had significantly higher 17-hydroxypregnenolone, 17-OHP, and DHEA sulfate concentrations. Cortisol values were not different between the sick and healthy preterm infants and were similar to full-term values. Aldosterone values were also similar between the premature and the full-term infants. The findings of elevated steroid precursors in preterm infants and low cortisol levels in stressed sick preterm infants may indicate a relative immaturity of adrenal enzyme activity and inadequate adrenal reserve for stress.

Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; 18-Hydroxycorticosterone; Aldosterone; Androstenedione; Birth Weight; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Gestational Age; Hormones; Humans; Hydrocortisone; Hydroxyprogesterones; Infant, Newborn; Infant, Premature; Male; Steroids

Premature induction of delivery in fetuses infused with graded doses of cortisol was brought about in 123.5 +/- 7.7 h (mean +/- SEM, n = 6) after the start of cortisol infusion. This treatment caused a rise in fetal plasma cortisol similar to that observed at normal delivery. Maternal and fetal progesterone and 20 alpha-dihydroprogesterone concentrations decreased to basal levels during infusion of cortisol to the fetus. Induction of premature delivery was delayed or prevented by concomitant treatment of the ewe with progestagen. Maternal intramuscular injection of 100 mg progesterone, 2 times daily, prevented delivery in four of four ewes treated during the time that cortisol was infused into the fetus (11-13 days). Maternal plasma progesterone and 20 alpha-dihydroprogesterone concentrations were maintained during this period, but fetal plasma progesterone concentrations decreased to the same extent as in the fetuses infused with cortisol alone. A single intramuscular injection of 250 mg of medroxyprogesterone acetate to ewes on the day before commencement of infusion of cortisol to the fetus prevented delivery in four of six ewes during the time that cortisol was infused for 9, 13, 14, and 15 days, respectively. One ewe delivered a live lamb at 133.5 h and another at 147.7 h after the start of infusion of cortisol to the fetus. Maternal and fetal plasma cortisol, progesterone, and 20 alpha-dihydroprogesterone concentrations were similar to those observed during infusion of cortisol alone to the fetus. Although fetal cortisol concentrations rose in a similar fashion, and to a similar extent, in all three groups during infusion of cortisol to the fetus, fetal 11-desoxycortisol concentrations only rose above basal levels close to the time of delivery in cortisol-infused fetuses or, in the progestagen-treated groups, when the fetus showed signs of being stressed.

Topics: 20-alpha-Dihydroprogesterone; Animals; Animals, Newborn; Birth Weight; Cortodoxone; Female; Fetal Blood; Fetus; Hydrocortisone; Medroxyprogesterone; Obstetric Labor, Premature; Pregnancy; Progesterone; Progestins; Sheep; Time Factors