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.