Placental abnormalities in congenital heart disease

Abstract

Congenital heart disease (CHD) remains the most common birth defect in infants, and critical CHD is associated with significant rates of morbidity and mortality. With the advent of powerful yet noninvasive advanced fetal imaging, it is becoming increasingly evident that the presence of CHD in utero disrupts typical development and contributes to the lifelong morbidity in this population. Across healthy and high-risk populations, intrauterine influences can permanently alter fetal development that may manifest in complex morbidities later in life, the so-called fetal-onset-of-adult-disease (FOAD) phenomenon. The placenta plays a critical role in not only supporting fetal development, but also by adapting to specific intrauterine conditions. The role of placental health, adaptation and dysfunction, however, in CHD is not well understood. In this article, we will review current evidence relating placental health in CHD, appraise existing knowledge-gaps in the field and highlight promising new avenues to better understand the impact of placental function on fetal well-being. We will review evidence of ex vivo human placental studies that describe abnormal placental findings in pregnancies complicated by CHD, as well evidence for in vivo assessments of the human placenta. While overall clinical in vivo assessments of placental development are rather limited, we will also review emerging evidence from advanced quantitative and functional magnetic resonance imaging that are bringing new insights into placental structure and function throughout gestation.By providing novel information about placental development, we can now explore the maternal-fetalplacental connection in greater detail, and better understand the multi-factorial mechanisms that may contribute to adverse outcomes seen in survivors of CHD.

Paternal obesity alters the sperm epigenome and is associated with changes in the placental transcriptome and cellular composition

“…Many of the DEGs in the paternal obese-sired placentas were involved in the regulation of the heart and brain. This is in line with paternal obesity associated to the developmental origins of neurological, cardiovascular, and metabolic disease in offspring (Andescavage & Limperopoulos, 2021; Binder et al, 2015, 2012; Chambers et al, 2016; Cropley et al, 2016; de Castro Barbosa et al, 2016; T. Fullston et al, 2012; Tod Fullston et al, 2013; Grandjean et al, 2015; Huypens et al, 2016; Jazwiec et al, 2022; Mitchell et al, 2011; Ng et al, 2010; Pepin et al, 2022; Perez-Garcia et al, 2018; Terashima et al, 2015; Thornburg et al, 2016; Thornburg & Marshall, 2015; Ueda et al, 2022; Wei et al, 2014). The brain-placenta and heart-placenta axes refer to their developmental linkage to the trophoblast which produces various hormones, neurotransmitters, and growth factors that are central to brain and heart development (Parrettini, Caroli, & Torlone, 2020; Rosenfeld, 2021).…”

“…The brain-placenta and heartplacenta axes refer to their developmental linkage to the trophoblast which produces various hormones, neurotransmitters, and growth factors that are central to brain and heart development (Parrettini, Caroli, & Torlone, 2020;Rosenfeld, 2021). This is further illustrated in studies where placental pathology is linked to cardiovascular and heart abnormalities (Andescavage & Limperopoulos, 2021;Thornburg et al, 2016;Thornburg & Marshall, 2015). For example, in a study of the relationship between placental pathology and neurodevelopment of infants, possible hypoxic conditions were a significant predictor of lower Mullen Scales of Early Learning (Ueda et al, 2022).…”

Epigenetics and Congenital Heart Diseases

“…Abnormal invasion results in preeclampsia, with a seven-fold risk increase observed in pregnancies complicated by heart defects [ 66 ]. Cord anomalies are particularly frequent in CHD, with a study citing a 13% incidence of fetal heart defects in single umbilical artery subjects [ 67 ], and similar overrepresentation of anomalous insertions in CHD cohorts (eccentric, marginal and velamentous insertions) [ 68 ]. Embryologically speaking, this association is referred to as the placenta–heart axis: these organs develop at identical timepoints and are the earliest necessary to pursue embryonic growth [ 69 ]; disruption on either side of this axis will result in aberrant morphological development, as evidenced by the microvasculature anomalies observed in CHD pregnancies, encompassing both maternal malformations (maternal vascular malperfusion, resulting from aberrant implantation) and fetal venous malperfusion (modifications in vasculature resulting from hypoxic/polyglobulic return to the placental unit in the context of cyanotic CHD) [ 68 , 69 ].…”

In Utero Brain Growth Matters for Fetuses With Congenital Heart Disease

“…The putative role of impaired placental function in pregnancies complicated by fetal CHD, including impaired oxygen transport resulting in reduced cerebral oxygen delivery and impaired brain development, necessitates further study. 14 This next frontier will undoubtedly be facilitated by recent advances in multimodal and multiorgan magnetic resonance imaging that have been applied successfully in the fetus with CHD. Psychological distress among pregnant women carrying fetuses with CHD is prevalent, but clinically underappreciated.…”