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.

Fig. 1. Normal placenta characterized by closely matched size and function to fetal needs compared to the inefficiency phenotype of fetal CHD.

This placenta is characterized by an inefficient function with vascular immaturity and a myriad of placental pathologic lesions, which leads to decreased cerebral blood flow beyond the autoregulatory capacity of the fetus with CHD, resulting in a small-to-normal size fetus with impaired brain development. CHD congenital heart disease.

Fig. 2. The placenta–heart–brain connection is modified by genetic/epigenetic, hemodynamic, and structural/microstructural influences.

These represent key areas for future investigations in the field of neuroplacentology in CHD.