Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes

Abstract

Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.

Cerebral Blood Flow Monitoring in High-Risk Fetal and Neonatal Populations

“…The adaptive cerebral vasodilation in the fetus with CHD results in a lower MCA PI, which may or may not be accompanied by placental insufficiency (130)(131)(132)(133)(134). Higher rates of placental pathologies are known to occur in pregnancies complicated by fetal CHD (135)(136)(137)(138)(139), therefore CPR requires careful interpretation in fetuses with CHD.…”

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study

“…Fetuses with CHDs are more vulnerable to a hypoxic environment, so there is increased importance in antenatal and postnatal development for CHD fetuses with placental malperfusion. 38 39 This study can contribute to improving prenatal detection of CHD by selecting high risk mothers with maternal serum markers for aneuploidy.…”

Associations Between Maternal Risk Factors and Intrinsic Placental and Fetal Brain Functional Properties in Congenital Heart Disease

“…Therefore, higher pBOLD temporal variance could correspond to a less cohesive hemodynamic response among the various placental cotyledons in CHD compared to non-CHD. This could explain varying response times of CHD placentas to hyperoxygenation stimulus 42 . Differences in spatial variance, seen in Figure 2, based on CHD status, may correspond to the prevalence of regional vascular impairments in each of the cotelydons.…”

“…In parallel, recent histopathological evidence has reported that placentas, in CHD, show a spectrum of pathological structural adaptations such as infarctions, chorangiosis, thrombosis and hypomature villi, suggesting vascular-related vulnerability and have been linked to the presence of postnatal brain injury, particularly in left ventricular outflow track obstruction heart lesion subtypes [7-11]. While these placental pathologies have been shown to correlate with newborn outcomes such as birthweight[8] and acquired postnatal brain injury, few direct associations have been found between placental abnormalities and neurodevelopmental outcomes in CHD.…”