Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes

Rachel L Leon,Imran N Mir,Diane M Twickler,Kavita Sharma,Christina L Herrera,Catherine Y Spong,Lina F Chalak

doi:10.1038/s41390-021-01521-7

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.ImpactNeuroplacentology 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.

Highlights

REVIEW ARTICLENeuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes
Congenital heart disease (CHD) affects an estimated 40,000 neonates annually in the United States, which is approximately 1% of all live births.[1,2] Many of the severe forms of CHD require surgical repair during the neonatal period or later in infancy
Using phasecontrast magnetic resonance imaging (MRI) and T2 mapping, Sun et al have shown that fetuses with severe forms of CHD have a lower oxygen saturation in the umbilical vein compared to controls and an overall 13% reduction in brain volume in fetal CHD subjects.[11]

Summary

REVIEW ARTICLE

Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. We summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. 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. ● Neuroplacentology seeks to understand placental connections to fetal brain development. ● 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

1234567890();,: INTRODUCTION

Placental inefficiency phenotype of severe CHD

Hemodynamics Structure

Findings

CONCLUSION