Fetal Cerebral Oxygenation Is Impaired in Congenital Heart Disease and Shows Variable Response to Maternal Hyperoxia

Shabnam Peyvandi, Duan Xu, Yan Wang, Whitnee Hogan, Anita Moon-Grady, A James Barkovich, Orit Glenn, Patrick McQuillen, Jing Liu, Shabnam Peyvandi, Duan Xu, Yan Wang, Whitnee Hogan, Anita Moon-Grady, A James Barkovich, Orit Glenn, Patrick McQuillen, Jing Liu

Abstract

Background Impairments in fetal oxygen delivery have been implicated in brain dysmaturation seen in congenital heart disease (CHD), suggesting a role for in utero transplacental oxygen therapy. We applied a novel imaging tool to quantify fetal cerebral oxygenation by measuring T2* decay. We compared T2* in fetuses with CHD with controls with a focus on cardiovascular physiologies (transposition or left-sided obstruction) and described the effect of brief administration of maternal hyperoxia on T2* decay. Methods and Results This is a prospective study performed on pregnant mothers with a prenatal diagnosis of CHD compared with controls in the third trimester. Participants underwent a fetal brain magnetic resonance imaging scan including a T2* sequence before and after maternal hyperoxia. Comparisons were made between control and CHD fetuses including subgroup analyses by cardiac physiology. Forty-four mothers (CHD=24, control=20) participated. Fetuses with CHD had lower total brain volume (238.2 mm3, 95% CI, 224.6-251.9) compared with controls (262.4 mm3, 95% CI, 245.0-279.8, P=0.04). T2* decay time was faster in CHD compared with controls (beta=-14.4, 95% CI, -23.3 to -5.6, P=0.002). The magnitude of change in T2* with maternal hyperoxia was higher in fetuses with transposition compared with controls (increase of 8.4 ms, 95% CI, 0.5-14.3, P=0.01), though between-subject variability was noted. Conclusions Cerebral tissue oxygenation is lower in fetuses with complex CHD. There was variability in the response to maternal hyperoxia by CHD subgroup that can be tested in future larger studies. Cardiovascular physiology is critical when designing neuroprotective clinical trials in the fetus with CHD.

Keywords: brain imaging; congenital heart disease; fetal.

Conflict of interest statement

None.

Figures

Figure 1. T2* fetal brain MRI.
Figure 1. T2* fetal brain MRI.
A, Images from 3 orthogonal plans were segmented and registered to obtain the final segmentation for T2* measurements at baseline and with MH; B, T2* decay curves for a control and CHD subject with hypoplastic left heart syndrome. The gestational age at fetal MRI was 33 3/7 weeks in the control subject and 34 2/7 weeks in the CHD subject. CHD indicates congenital heart disease; MH, maternal hyperoxia; and MRI, magnetic resonance imaging.
Figure 2. Flowchart of participants included in…
Figure 2. Flowchart of participants included in the study.
CHD indicates congenital heart disease; and MRI, magnetic resonance imaging.
Figure 3. T2* values at baseline for…
Figure 3. T2* values at baseline for the control, LSOL, and TGA groups with mean and 95% CI.
At baseline, cerebral tissue oxygenation (T2*) is significantly lower in LSOL (**coeff:−15.4, 95% CI, −25.3 to −5.5, P=0.003) and TGA (*coeff: −12.0, 95% CI, −24.4 to 0.4, P=0.05) compared with the control group after adjusting for gestational age at MRI. LSOL indicates left‐sided obstructive lesions; MRI, magnetic resonance imaging; and TGA, transposition of the great arteries.
Figure 4. The magnitude of change in…
Figure 4. The magnitude of change in T2* from baseline to MH testing for the control (black line: mean; gray lines: individual patients), transposition of the great arteries (TGA) (blue line: mean; light blue lines: individual patients), and LSOL (red line: mean; light red lines: individual patients).
LSOL indicates left‐sided obstructive lesions; MH, maternal hyperoxia; and TGA, transposition of the great arteries.

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