3-D volumetric MRI evaluation of the placenta in fetuses with complex congenital heart disease
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.
Section snippets
Subjects
Subjects were recruited prospectively into a longitudinal, observational study in which MRI was performed up to two time points in the fetal period, and in the immediate neonatal period. This report includes data from the fetal evaluation(s).
Pregnant women carrying fetuses with confirmed CHD were recruited from the Fetal Heart Program at Children's National Medical Center. Normal controls were recruited from healthy volunteers with a normal prenatal history that included normal screening
Characteristics of our cohort
A total of 135 pregnant women were enrolled, 94 healthy controls and 41 with pregnancies complicated by CHD. Twenty-five women had two fetal MRI studies, for a total of 160 scans (112 controls and 48 cases of CHD). Of these, 5 scans from the CHD group were excluded because the fetuses were subsequently diagnosed with significant extra-cardiac anomalies (2 DiGeorge syndrome, 1 chromosomal anomaly and 2 with pulmonary agenesis) and 1 CHD scan had incomplete MRI data. In the remaining 155 studies
Discussion
In this prospective study, we investigated the relationship between altered fetal hemodynamics and placental growth by evaluating placental volume in the fetus with CHD. Using MRI to assess placental growth in the fetus with CHD, we found little evidence that placental volume differs between CHD and healthy fetuses during gestation. As expected, placental volume increased with gestational age at birth and birth weight; not expected was that the growth in placental volume in relation to birth
Sources of funding
This work was supported by the Canadian Institutes of Health Research (MOP-81116) and by the Intellectual and Developmental Disabilities Award (NICHD-2P30HD040677-11) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Contributors
Each author contributed to this work in the following capacity:
Nickie Andescavage: I declare that I participated in the study design; data acquisition and analysis; manuscript preparation and editing and that I have seen and approved the final version. I have no conflicts of interest to disclose.
Alexa Yarish: I declare that I participated in the data analysis and manuscript editing and that I have seen and approved the final version. I have no conflicts of interest to disclose.
Mary Donofrio: I
Acknowledgments
We thank our families who participated in this study. We thank Ahmed Serag, Neer Hershtig, Dena Freeman, and Lauren Crowder for their assistance in this project.
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