ACTIVATION OF THE FETAL HYPOTHALAMIC-PITUITARY-ADRENAL AXIS WITH PROLONGED AND GRADED HYPOXEMIA

OBJECTIVE: The purpose of this study was to determine whether activati on of the hypothalamic-pituitary-adrenal (HPA) axis and uteroplacental prostaglandin (PG) response occur before metabolic deterioration with a progressive decrease in fetal oxygenation. METHODS: Twenty-one chro nically catheterized fetal sheep were studied between 126 and 135 days ' gestation during a 24-hour normoxic control period and subsequently during 4 experimental days of either prolonged and graded hypoxemia, i nduced by progressively lowering the maternal inspired oxygen concentr ation (induced hypoxia, n = 12), or continued study on room air (contr ol, n = 6; spontaneous hypoxia, n = 3). Fetal arterial blood was sampl ed daily for blood gases and pH, immunoreactive ACTH, cortisol, and PG E(2). Placental cotyledons were obtained at the end of the experiment for measurement of prostaglandin-H synthase (PGHS) enzymatic activity. RESULTS: For all hypoxia group measurements, progressive reduction in fetal oxygenation resulted in little change in either plasma ACTH or cortisol until arterial O-2 saturation was close to 30% with metabolic acidosis onsetting. This was in keeping with activation of the HPA ax is at this time, because ACTH and cortisol values showed a strong line ar correlation (r = 0.77, P <.01). Fetal plasma PGE(2) concentrations and cotyledonary PGHS enzymatic activity, although somewhat higher in the hypoxia group animals, were not changed significantly. CONCLUSION: In response to prolonged and graded hypoxemia in the ovine fetus, act ivation of the HPA. axis occurs only when the degree of hypoxemia is p ronounced and close to that associated with metabolic deterioration, w hich may limit the time for any uteroplacental response and the abilit y to initiate labor. Copyright (C) 1997 by the Society for Gynecologic Investigation.