Cortisol and ACTH responses to severe asphyxia in preterm fetal sheep

It has been hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis is immature in the preterm fetus and that this compromises their ability to adapt to hypoxic stress; however, there are few direct data. We therefore examined the effects of asphyxia on HPA responses in chronically instrumented preterm fetal sheep (104 days of gestation; term is 147 days), allocated to a sham control group (n= 7) or 25 min of complete umbilical cord occlusion (n= 8), followed by recovery for 72 h. During umbilical cord occlusion there was a rapid rise in ACTH levels (230.4 ± 63.5 versus 14.1 ± 1.8 ng ml−1 in sham controls, 16-fold) and cortisol levels (7.4 ± 4.9 versus 0.2 ± 0.1 ng ml−1, 31-fold), with further increases after release of cord occlusion. ACTH levels were normalized by 24 h, while plasma cortisol levels returned to sham control values 72 h after asphyxia. Fetal arterial blood pressure was elevated in the first 36 h, with a marked increase in femoral vascular resistance, and correlated positively with cortisol levels after asphyxia (P= 0.05). In conclusion, the preterm fetus shows a brisk, substantial HPA response to severe hypoxia.