Autoregulation of Cerebral Blood Flow in Fetuses with Congenital Heart Disease: The Brain Sparing Effect

Abstract

Fetuses with congenital heart disease (CHD) have circulatory abnormalities that may compromise cerebral oxygen delivery. We believe that some CHD fetuses with decreased cerebral oxygen supply have autoregulation of blood flow that enhances cerebral perfusion (brain sparing). We hypothesize that cerebral autoregulation occurs in CHD fetuses, and the degree of autoregulation is dependent on the specific CHD and correlates with intrauterine head circumferences. CHD fetuses were compared to normal fetuses. Data included cardiac diagnosis, cerebral and umbilical artery Doppler, head circumference, weight, and gestational age. The cerebral-to-placental resistance ratio (CPR) was assessed as a measure of cerebral autoregulation. CPR = cerebral/umbilical resistance index (RI) and RI = systolic-diastolic/systolic velocity (normal CPR > 1). CPR > 1 was found in 95% of normal vs 44% of CHD fetuses. The incidence of CPR < 1 was greatest in hypoplastic left or right heart fetuses. Compared to normal, cerebral RI was decreased in CHD fetuses. The CPR vs gestational age relationship, and the relationship among weight, head circumference, and CPR differed across normal and CHD fetuses. Fetuses > 2 kg with CHD and a CPR < 1 had smaller head circumferences than normal. Brain sparing occurs in CHD fetuses. Fetuses with single ventricular physiology are most affected. Inadequate cerebral flow in CHD fetuses, despite autoregulation, may alter brain growth.

Prevalence and Spectrum of In Utero Structural Brain Abnormalities in Fetuses with Complex Congenital Heart Disease

“…14,15 Using Doppler sonography, Donofrio et al 15 compared the cerebralplacental ratio between fetuses with CHD and healthy controls and showed that the normal intrinsic cerebral compensatory response to insufficient oxygen-substrate delivery (ie, cerebral vasodilation) was activated in fetuses with CHD. The cerebral-placental ratio was significantly lower overall in fetuses with CHD, with values Ͻ1.0 most prevalent in fetuses with a single-ventricle physiology.…”

Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome

“…Mortality and G-tube placement data were available for 99 (94%) and 81 (78%) cases, respectively. A total of 53 infants were excluded for associated cardiac anatomy (29), prematurity (17), twinning (4), and genetic syndromes (3).…”

“…Abnormal MCA blood flow has been observed in fetuses with evolving HLHS (21,29,30), but the clinical significance of this finding is unclear. Currently, some centers advocate fetal intervention in fetuses with severe valvar aortic stenosis in order to improve antegrade blood flow across the aortic valve, postulating that this forward flow may prevent the progression of aortic stenosis to HLHS and result in better neurodevelopmental outcomes (31).…”

Imaging selective vulnerability in the developing nervous system

“…Neuropathology data in newborns with CHD also indicate that they are more likely to be microcephalic and have an immature cortical mantle (Glauser et al 1990). Newborns with D-transposition of the great arteries and single ventricle physiology have impaired in-utero brain growth, possibly related to impaired fetal cerebral oxygen delivery (Donofrio et al 2003;Limperopoulos et al 2010). …”