Development and Mechanisms of Fetal Hypoxia in Severe Fetal Growth Restriction

Severe fetal growth restriction (FGR) is often associated with hypoxia. We studied FGR hypoxia in an experimental model which is produced by exposing pregnant ewes to a hyperthermic environment. The study utilized simultaneous measurements of several relevant factors, e.g., uterine and umbilical blood flows and O2 uptakes. Sixteen ewes were divided equally into control (C) and hyperthermic (HT) groups. Hyperthermia (40 °C for 12 h/35 °C for 12 h; ∼35% relative humidity, RH) was maintained for 80 days commencing at approximately 38 days gestational age (dGA term 147 ± 3 days). All ewes were then placed in a control environment (∼21 °C, 24 h; ∼30% RH) and studied at approximately 134 dGA. Mean HT placental and fetal weights were 39% and 45% of C, respectively (p < 0.0001), umbilical O2 uptake/kg fetus was 76% of C (p < 0.01) and umbilical venous PO2 was reduced (20.2 vs. 29.7 Torr, p < 0.001). Contrary to the hypothesis that FGR hypoxia is due to maternal placental hypoperfusion, uterine flow was not reduced in relation to O2 uptake. The uterine-umbilical venous PO2 difference was enlarged (38 vs. 23 Torr, p < 0.0001). This difference is the expression of a balance between developmental changes in placental structure and oxidative metabolism, which have opposite effects in terms of fetal oxygenation. We postulate that FGR hypoxia results from disproportionate underdevelopment of those changes which allow for a progressive increase in umbilical O2 uptake.