3-D volumetric MRI evaluation of the placenta in fetuses with complex congenital heart disease

Highlights

• We examine placental volume in congenital heart disease using magnetic resonance imaging.

• Placental volume increases with advancing gestational age.

• Placental volume is positively associated with birth weight.

• Placental volume is positively associated with gestational age at birth.

• Placental volume is not associated with fetal brain volume.

Abstract

Introduction

Placental insufficiency remains a common cause of perinatal mortality and neurodevelopmental morbidity. Congenital heart disease (CHD) in the fetus and its relationship to placental function is unknown. This study explores placental health and its relationship to neonatal outcomes by comparing placental volumes in healthy pregnancies and pregnancies complicated by CHD using in vivo three-dimensional MRI studies.

Methods

In a prospective observational study, pregnant women greater than 18 weeks gestation with normal pregnancies or pregnancies complicated by CHD were recruited and underwent fetal MR imaging. The placenta was manually outlined and the volume was calculated in cm³. Brain volume was also calculated and clinical data were also collected. Relationships, including interactive effects, between placental and fetal growth, including brain growth, were evaluated using longitudinal multiple linear regression analysis.

Results

135 women underwent fetal MRI between 18 and 39 weeks gestation (mean 31.6 ± 4.4). Placental volume increased exponentially with gestational age (p = 0.041). Placental volume was positively associated with birth weight (p < 0.001) and increased more steeply with birth weight in CHD-affected fetuses (p = 0.046). Total brain and cerebral volumes were smaller in the CHD group (p < 0.001), but brainstem volume (p < 0.001) was larger. Placental volumes were not associated with brain volumes.

Discussion

Impaired placental growth in CHD is associated with gestational age and birth weight at delivery. Abnormalities in placental development may contribute to the significant morbidity in this high-risk population. Assessment of placental volume by MRI allows for in vivo assessments of placental development.

Introduction

Placental function and a well-controlled intrauterine environment are critical for normal neurodevelopment of the fetus [1], [2]. Placental insufficiency can compromise the developing fetus by limiting essential nutrient transfer from the mother, allowing for the transfer of toxic substrates to the fetus or diminishing the neuroendocrine function of the placenta [1], [3], [4], [5]. Despite its critical function, placental insufficiency remains difficult to identify until after the fetus has been compromised by growth restriction or abnormalities have developed in the umbilical or fetal vascular network. While it is known that placental insufficiency is a complication of maternal vascular disease that impairs uterine blood flow [6], [7], [8], [9] as well as a complication of abnormal placental implantation and vascular development [10], [11], [12], the relationship between fetal vascular disease and placental health is unknown. Fetal vascular disease, as in congenital heart disease (CHD), can result in alterations in oxygen delivery and blood flow in the fetal and placental circulation [13]. Much less is known about the effect of fetal vascular abnormalities associated with CHD on placental growth and function.

As mortality rates continue to decrease dramatically in newborns diagnosed with complex CHD, long-term neurodevelopmental impairments are recognized with increased frequency in surviving infants. Motor and cognitive disabilities, as well as neurosensory and psychosocial impairments are frequently described in children with complex CHD [14]. In addition to the genetic predisposition for structural brain anomalies in the patient with CHD, there is a growing body of evidence that supports acquired brain injury in this population. It is now well established that brain injury is multi-factorial and includes several periods of risks including intraoperative events and postoperative complications, in addition to postnatal pre-operative vulnerability for neonatal brain injury [14], [15]. Advances in fetal imaging, and particularly magnetic resonance imaging (MRI) have recently provided important insights into abnormal intrauterine neurodevelopment in the fetus with CHD. Abnormalities in the fetal circulation due to CHD disrupt oxygen and substrate delivery to the cerebral circulation, which further disrupt cerebral perfusion [14]. In addition, alterations in the fetal circulation due to CHD have also been associated with blood flow abnormalities of the umbilical vessels [16], [17], [18]. Evaluation of the cerebral-placental vascular bed in CHD using Doppler measures of the middle cerebral arteries, umbilical arteries and cerebro-placental ratio has revealed decreased resistance of blood flow in the cerebral arteries as well as significant abnormalities of the cerebro-placental ratio [19]. These changes are similar to those reported in placental insufficiency and intrauterine growth restriction, another population that has high perinatal mortality and neurodevelopmental morbidity [20]. Though the placenta has been studied in growth restriction, to date no study has examined placental growth in fetuses diagnosed with complex CHD in utero.

The objective of this investigation was to compare placental volumes in healthy pregnancies and those complicated by complex CHD using in vivo three-dimensional MRI studies, and to delineate clinical and hemodynamic effects associated with impaired placental growth. We hypothesized that [1] placental growth in the fetus with CHD would be diminished in the second and third trimesters compared to healthy controls [2], impaired placental growth in CHD will be associated with impaired fetal brain growth and [3] impaired placental growth in CHD will be associated with known adverse neonatal outcomes of placental insufficiency.