Differential fetal adrenal response in congenital heart disease based on cerebral oxygen delivery

To evaluate fetal adrenal gland, neocortex, and fetal zone volumes using 2D ultrasound in pregnancies affected by congenital heart disease (CHD).

This prospective case-control study included 65 fetuses with CHD and 65 gestational age-matched healthy controls. Volumes of the whole adrenal gland (WAGV), fetal zone (FZV), and neocortex (NCV) were calculated using 2D ultrasound and corrected for estimated fetal weight. The CHD group was subdivided into Class A (reduced cerebral oxygen delivery, n=33) and Class B (normal cerebral oxygen delivery, n=32). Corrected volumes (c-WAGV, c-FZV, c-NCV) were compared between groups.

Fetuses with CHD had larger corrected WAGV (c-WAGV: 0.41 ± 0.12 vs. 0.30 ± 0.06, p=0.001) and neocortex volumes (c-NCV: 0.35 ± 0.11 vs. 0.25 ± 0.06, p=0.001) than healthy controls, while fetal zone volumes were similar. Both Class A (0.30 ± 0.07) and Class B (0.39 ± 0.12) showed increased neocortex volumes compared with controls (0.25 ± 0.06); however, Class A fetuses had smaller neocortex volumes than Class B (p=0.002).

CHD is associated with enlargement of the fetal adrenal neocortex, reflecting chronic activation of the fetal HPA axis. However, fetuses with low cerebral oxygen levels show a weaker response, suggesting that severe hypoxia may limit the development of the fetal stress system. Adrenal volume assessment may provide insight into intrauterine stress severity in CHD.