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-fetal-placental connection in greater detail, and better understand the multi-factorial mechanisms that may contribute to adverse outcomes seen in survivors of CHD.

Keywords: Placenta; congenital heart disease (CHD); imaging; magnetic resonance imaging; ultrasound.

Figure 1

A diagram of the Fetal-Heart Placenta Axis, where fetal hypoxia and circulatory changes from congenital heart disease may contribute to placental insufficiency (red arrow), while ongoing placental insufficiency may further contribute to worsening fetal hypoxia, growth retardation and adverse intrauterine programming (blue arrow).

Figure 2

A diagram of placental efficiency. Panel (A) shows a typically developing fetus and placenta (appropriate for gestational age, AGA), while panel (B) shows a smaller placenta relative to fetal development, that would result in a lower placental weight (PW) to birth weight (BW) ratio. A reduced PW:BW ratio may reflect a highly efficient placenta that can support adequate fetal growth despite smaller placental size.

Figure 3

Three-dimensional reconstructions of in vivo placentas from MRI images, with the cord insertion site highlighted by a white arrow. Panel (A) demonstrates a placenta with central cord insertion site, and relatively symmetric fetal surface radii, while Panel (B) demonstrates a placenta with eccentric cord insertion site, and asymmetric fetal surface radii. These metrics have been used to develop a cord centricity score (unpublished data), as eccentric cord insertion sites are associated with growth disturbances of both the infant and placenta.

Figure 4

Anatomic (A) and arterial spin labeling images (ASL) (B) of the placenta in a pregnant woman with fetal congenital heart disease diagnosis, with the placenta outlined by the dotted line.

Figure 5

Anatomic image of fetus and placenta (A) and blood oxygen level dependent (BOLD) image of fetus and placenta (B) at 36 weeks gestation. Panel B highlights the fetal brain (red) and placenta (green) as regions of interest to measure BOLD signal. The maternal hyperoxia design collects BOLD signal at baseline, during maternal hyperoxia, and during return to baseline. Differences in BOLD signal reflect differences in regional oxygenation during each phase, which can be used to assess both baseline oxygenation, as well as capacity for oxygen transfer from mother to placenta and then fetus.