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Changes in Adrenocorticotropin and Cortisol Responsiveness after Repeated Partial Umbilical Cord Occlusions in the Late Gestation Ovine Fetus¹

Laboratory for Pregnancy and Newborn Research, Department of Physiology, New York State College of Veterinary Medicine, Cornell University (N.U., D.A.G., W.K.H.M.A.H., X.Y.D., P.W.N.), Ithaca, New York 14853-6401; and Obstetrics and Gynecology (J.H.C.), Slidel, Louisiana 70461

Address all correspondence and requests for reprints to: Dr. Peter W. Nathanielsz, Laboratory for Pregnancy and Newborn Research, Department of Physiology, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401. E-mail: pwn1{at}cornell.edu

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.

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