Association of Prenatal Diagnosis of Critical Congenital Heart Disease With Postnatal Brain Development and the Risk of Brain Injury

Abstract

Importance: The relationship of prenatal diagnosis of critical congenital heart disease (CHD) with brain injury and brain development is unknown. Given limited improvement of CHD outcomes with prenatal diagnosis, the effect of prenatal diagnosis on brain health may reveal additional benefits.

Objective: To compare the prevalence of preoperative and postoperative brain injury and the trajectory of brain development in neonates with prenatal vs postnatal diagnosis of CHD.

Design, setting, and participants: Cohort study of term newborns with critical CHD recruited consecutively from 2001 to 2013 at the University of California, San Francisco and the University of British Columbia. Term newborns with critical CHD were studied with brain magnetic resonance imaging preoperatively and postoperatively to determine brain injury severity and microstructural brain development with diffusion tensor imaging by measuring fractional anisotropy and the apparent diffusion coefficient. Comparisons of magnetic resonance imaging findings and clinical variables were made between prenatal and postnatal diagnosis of critical CHD. A total of 153 patients with transposition of the great arteries and single ventricle physiology were included in this analysis.

Main outcomes and measures: The presence of brain injury on the preoperative brain magnetic resonance imaging and the trajectory of postnatal brain microstructural development.

Results: Among 153 patients (67% male), 96 had transposition of the great arteries and 57 had single ventricle physiology. The presence of brain injury was significantly higher in patients with postnatal diagnosis of critical CHD (41 of 86 [48%]) than in those with prenatal diagnosis (16 of 67 [24%]) (P = .003). Patients with prenatal diagnosis demonstrated faster brain development in white matter fractional anisotropy (rate of increase, 2.2%; 95% CI, 0.1%-4.2%; P = .04) and gray matter apparent diffusion coefficient (rate of decrease, 0.6%; 95% CI, 0.1%-1.2%; P = .02). Patients with prenatal diagnosis had lower birth weight (mean, 3184.5 g; 95% CI, 3050.3-3318.6) than those with postnatal diagnosis (mean, 3397.6 g; 95% CI, 3277.6-3517.6) (P = .02). Those with prenatal diagnosis had an earlier estimated gestational age at delivery (mean, 38.6 weeks; 95% CI, 38.2-38.9) than those with postnatal diagnosis (mean, 39.1 weeks; 95% CI, 38.8-39.5) (P = .03).

Conclusions and relevance: Newborns with prenatal diagnosis of single ventricle physiology and transposition of the great arteries demonstrate less preoperative brain injury and more robust microstructural brain development than those with postnatal diagnosis. These results are likely secondary to improved cardiovascular stability. The impact of these findings on neurodevelopmental outcomes warrants further study.

Figure 1. Preoperative and Postoperative Brain Injury Severity by Postnatal vs Prenatal Diagnosis of Critical Congenital Heart Disease

Brain injury severity on preoperative magnetic resonance imaging (MRI) in patients with postnatal (A) and prenatal (B) diagnosis of critical congenital heart disease as well as on postoperative MRI in patients with postnatal (C) and prenatal (D) diagnosis of critical congenital heart disease. Brain injury severity was assigned as the following: 0 indicates no injury; 1, minimal white matter injury and intraventricular hemorrhage grade I or II; 2, stroke; and 3, moderate to severe white matter injury, intraventricular hemorrhage grade III, or global hypoxic-ischemic brain injury. A test for trends demonstrates a significant trend toward less severe brain injury on preoperative MRI in the prenatal diagnosis group (P = .02). There was no meaningful difference in new postoperative brain injury severity (P = .40).

Figure 2. Scatterplots and Linear Regression Lines of Change in the Log of Fractional Anisotropy and the Log of Apparent Diffusion Coefficient

Scatterplots and linear regression lines of change in the fractional anisotropy in white matter voxels (A) and apparent diffusion coefficient in gray matter voxels (B) demonstrate a faster rate of increase in fractional anisotropy (P = .04) and a faster rate of decrease in apparent diffusion coefficient (P = .02) in patients with prenatal diagnosis of critical congenital heart disease than in those with postnatal diagnosis. Time is defined as the gestational age when magnetic resonance imaging (MRI) was performed (includes both preoperative and postoperative scans).