Changes in Adrenocorticotropin and Cortisol Responsiveness after Repeated Partial Umbilical Cord Occlusions in the Late Gestation Ovine Fetus

Despite many studies reporting fetal ACTH and cortisol (F) responses to acute fetal hypoxemia induced by several methods, effects of repeated short-term fetal hypoxia produced by umbilical cord occlusion (UCO) on ACTH and F are unknown. We examined fetal ACTH and F responses to repeated, controlled, 50% reductions in common umbilical arterial blood flow (CUBF) produced by an inflatable cord occluder. Ten sheep fetuses were instrumented at 123-128 days gestation (dGA) with arterial, venous, and amniotic catheters. A common umbilical artery transit-time ultrasound flow probe was implanted to measure CUBF. An inflatable occluder was placed around the proximal portion of the umbilicus. In five fetuses (group I) at 131 +/- 1 dGA (mean +/- SEM), 12 UCOs (CUBF reduced by 50%), each lasting 5 min separated by 15 min recovery, were performed. Changes in fetal arterial blood gases, pH and plasma ACTH, and F concentrations were determined before, during, and after the 1st, 6th, and 12th UCOs. Sham experiments were conducted on the other five fetuses at 130 +/- 1 dGA (group II). In group I, CUBF decreased to 49 +/- 1% (mean +/- SEM of 12 UCOs). After each UCO, CUBF returned to baseline within 5 min. A modest fall in fetal arterial PO2 and arterial pH (21.2 +/- 0.2 to 16.8 +/- 0.2 mmHg and 7.33 +/- 0 to 7.29 +/- 0, respectively) and a mild increase in fetal PaCO2 (49.9 +/- 0.5 to 54.9 +/- 0.4 mmHg; mean +/- SEM of 12 UCOs) occurred with each UCO. Whereas preocclusion fetal ACTH concentrations increased by the 12th UCO, F remained unchanged. Fetal ACTH increased after the 1st, 6th, and 12th UCOs. Fetal F increased after the 1st and 6th UCOs but not after the 12th UCO. Fetal plasma ACTH and F remained unchanged throughout the experiments in group II fetuses. We conclude that: 1) partial reductions in CUBF induce significant activation of the fetal anterior pituitary-adrenocortical axis in late-gestation fetal sheep; 2) after repeated UCOs, fetal ACTH responsiveness is maintained, but fetal F responses become attenuated.