Associations between Maternal Risk Factors and Intrinsic Placental and Fetal Brain Functional Properties in Congenital Heart Disease

Abstract

The relationship between maternal risk factors (MRFs) (particularly pre-gravid obesity, diabetes, and hypertension) and congenital heart disease (CHD) to placental and fetal brain outcomes is poorly understood. Here, we tested the hypothesis that MRF and CHD would be associated with reduced intrinsic placental and fetal brain function using a novel non-invasive technique. Pregnant participants with and without MRF and fetal CHD were prospectively recruited and underwent feto-placental MRI. Using intrinsic properties of blood oxygen level dependent imaging (BOLD) we quantified spatiotemporal variance of placenta and fetal brain. MRFs and CHD were correlated with functional characteristics of the placenta and fetal brain. Co-morbid MRF (hypertension, diabetes, and obesity) reduced spatiotemporal functional variance of placenta and fetal brain (p < 0.05). CHD predicted reduced fetal brain temporal variance compared to non-CHD (p < 0.05). The presence of both MRF and CHD was associated with reduced intrinsic pBOLD temporal variance (p = 0.047). There were no significant interactions of MRFs and CHD status on either temporal or spatial variance of intrinsic brain BOLD. MRF and CHD reduced functional characteristic of placenta and brain in fetuses. MRF modification and management during pregnancy may have the potential to not only provide additional risk stratification but may also improve neurodevelopmental outcomes.

Angiogenic imbalance in maternal and cord blood is associated with neonatal birth weight and head circumference in pregnancies with major fetal congenital heart defect

“…In previous work, we observed altered expression of angiogenesis markers in the brain tissue of fetuses with CHD that had undergone termination of pregnancy 26 . Since management of maternal risk factors during pregnancy may have the potential to improve neurodevelopmental outcome 37 , one possible explanation that warrants further evaluation is that impaired angiogenesis can affect brain development and maturation in fetal and also postnatal life.…”

Interdependence of placenta and fetal cardiac development

“…92 Although limited in number, these MRI studies have demonstrated associations between abnormalities in placental functional characteristics and fetal hemodynamics, particularly in the brain. 89,[92][93][94] Although these MRI studies are cross-sectional and involve small sample sizes, they establish the proof of concept that placental functional impairments can be measured prenatally in CHD. This underscores the critical need for larger longitudinal studies aimed at characterizing the ontogeny and progression of placental functional impairments in CHD, ultimately aiming to translate placental MRI from a research tool to a clinical diagnostic standard that will drive the development of targeted therapeutics.…”

“…CHD placentas have been observed to exhibit reduced baseline oxygenation, 89,90 perfusion, 91 and altered hemodynamic responses to maternal hyperoxia stimuli 92 . Although limited in number, these MRI studies have demonstrated associations between abnormalities in placental functional characteristics and fetal hemodynamics, particularly in the brain 89,92–94 . Although these MRI studies are cross‐sectional and involve small sample sizes, they establish the proof of concept that placental functional impairments can be measured prenatally in CHD.…”

“…While predominantly utilized for research purposes, current MRI modalities exploit placental vascularity and oxygenation as surrogates for overall placental function. CHD placentas have been observed to exhibit reduced baseline oxygenation, 89,90 perfusion, 91 and altered hemodynamic responses to maternal hyperoxia stimuli 92 . Although limited in number, these MRI studies have demonstrated associations between abnormalities in placental functional characteristics and fetal hemodynamics, particularly in the brain 89,92–94 .…”