Hemodynamic Responses of the Placenta and Brain to Maternal Hyperoxia in Fetuses with Congenital Heart Disease by Using Blood Oxygen-Level Dependent MRI

Abstract

Background Impaired brain development in fetuses with congenital heart disease (CHD) may result from inadequate cerebral oxygen supply in utero. Purpose To test whether fetal cerebral oxygenation can be increased by maternal oxygen administration, effects of maternal hyperoxia on blood oxygenation of the placenta and fetal brain were examined by using blood oxygenation level-dependent (BOLD) functional MRI. Materials and Methods In this prospective study, BOLD MRI was performed in 86 fetuses (56 healthy fetuses and 30 fetuses diagnosed with CHD) between 22 and 39 weeks gestational age (GA) from May 2015 to December 2017, with the following study design: phase I, 2-minute resting state at baseline (room air); phase II, 6-minute maternal hyperoxia with 100% oxygen; and phase III, 5.6-minute return to resting state. After motion correction, the signals were averaged over the placenta and fetal brain and converted to the change in R2* (ΔR2*). Fetuses with CHD were categorized into those with a single ventricle (SV) or two ventricles (TVs) and those with aortic obstruction (AO) or non-AO. Data were analyzed by using generalized linear mixed models controlling for GA and sex. Results Placental ΔR2* increased during maternal hyperoxia in healthy fetuses and fetuses with CHD, but it was higher in SV CHD (mean ΔR2*, 1.3 sec^-1 ± 0.1 [standard error; P < .01], 1.9 sec^-1 ± 0.2 [P < .01], and 1.0 sec^-1 ± 0.3 [P < .01], respectively, for control fetuses, fetuses with SV CHD, and fetuses with TV CHD). Placental ΔR2* during maternal hyperoxia changed with GA in healthy control fetuses and fetuses with SV or AO CHD (ΔR2* per week, 0.1 sec^-1 ± 0 [P < .01], 0.2 sec^-1 ± 0 [P = .01], and 0.2 sec^-1 ± 0 [P = .01], respectively), but not in fetuses with CHD and TV or non-AO. Fetal brain ΔR2* was constant across all phases in healthy control fetuses and fetuses with TV CHD but increased during maternal hyperoxia in fetuses with SV or AO CHD (mean ΔR2*, 0.7 sec^-1 ± 0.2 [P = .01] and 0.5 sec^-1 ± 0.2 [P = .02], respectively). Conclusion Six minutes of maternal hyperoxia increased placental oxygenation in healthy fetuses and fetuses with congenital heart disease, and it selectively increased cerebral blood oxygenation in fetuses with single ventricle or aortic obstruction. © RSNA, 2019 Online supplemental material is available for this article.

Graphical abstract

Figure 1:

Flowchart for the selection of study subjects from the enrolled pregnant women in the Children’s National Hospital. CHD = congenital heart disease.

Figure 2:

Coronal image from functional MRI from a normal pregnancy of a single female fetus at 35 gestational weeks. The red lines show the regions of interest for the placenta and fetal brain acquired during maternal hyperoxia.

Figure 3:

Graphs show the changes in R2* of the, A, placenta and, B, fetal brain at resting state (RS) during maternal hyperoxia (HO) and during return to resting state (RR) in normal pregnancies and those complicated by congenital heart disease (CHD) with single ventricle (SV) or two ventricles (2V). Data for ΔR2* are expressed as means and standard errors. HO1–HO6 = each minute of HO, RR1–RR6 = each minute of RR.

Figure 4:

Comparison of voxel-wise placental change in R2* (ΔR2*) in resting state (left), after 6 minutes of hyperoxia (middle), and after 5 minutes of return to resting state (right) between healthy pregnancies and pregnancies complicated by congenital heart disease (CHD) with single ventricle (SV) or two ventricles (2V). The color map indicates the magnitude of ΔR2*.

Figure 5:

Comparison of voxel-wise change in R2* (ΔR2*) in fetal brain in resting state (left), after 6 minutes of hyperoxia (middle), and after 5 minutes of return to resting state (right) between healthy pregnancies and pregnancies complicated by congenital heart disease (CHD) with single ventricle (SV) or two ventricles (2V). The color map indicates the magnitude of ΔR2*.

Figure 6:

Scatterplots show comparison of placental change in R2* (ΔR2*; after 6 minutes of maternal hyperoxia [HO6] phase) versus gestational age between, A, normal pregnancies and those complicated by congenital heart disease with, B, single ventricle or, C, two ventricles. Data points and linear regression lines are plotted.