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Observational Study
. 2023 Oct 17;82(16):1614-1623.
doi: 10.1016/j.jacc.2023.08.013.

Magnetic Resonance Spectroscopy of Brain Metabolism in Fetuses With Congenital Heart Disease

Nickie N Andescavage  1 , Subechhya Pradhan  2 , Alexis C Gimovsky  3 , Kushal Kapse  2 , Mary T Donofrio  4 , Jenhao Jacob Cheng  5 , Yushuf Sharker  2 , David Wessel  6 , Adre J du Plessis  7 , Catherine Limperopoulos  8
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Free article
Observational Study

Magnetic Resonance Spectroscopy of Brain Metabolism in Fetuses With Congenital Heart Disease

Nickie N Andescavage et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Congenital heart disease (CHD) remains a significant risk factor for neurologic injury because altered fetal hemodynamics may be unable to support typical brain development during critical periods of growth and maturation.

Objectives: The primary objective was to assess differences in the cerebral biochemical profile between healthy fetuses and fetuses with complex CHD and to relate these with infant outcomes.

Methods: Pregnant participants underwent fetal magnetic resonance imaging with cerebral proton magnetic resonance spectroscopy acquisitions as part of a prospective observational study. Cerebral metabolites of N-acetyl aspartate, creatine, choline, myo-inositol, scyllo-inositol, lactate, and relevant ratios were quantified using LCModel.

Results: We acquired 503 proton magnetic resonance spectroscopy images (controls = 333; CHD = 170) from 333 participants (controls = 221; CHD = 112). Mean choline levels were higher in CHD compared with controls (CHD 2.47 IU [Institutional Units] ± 0.44 and Controls 2.35 IU ± 0.45; P = 0.02), whereas N-acetyl aspartate:choline ratios were lower among CHD fetuses compared with controls (CHD 1.34 ± 0.40 IU vs controls 1.44 ± 0.48 IU; P = 0.001). Cerebral lactate was detected in all cohorts but increased in fetuses with transposition of the great arteries and single-ventricle CHD (median: 1.63 [IQR: 0.56-3.27] in transposition of the great arteries and median: 1.28 [IQR: 0-2.42] in single-ventricle CHD) compared with 2-ventricle CHD (median: 0.79 [IQR: 0-1.45]). Cerebral lactate also was associated with increased odds of death before discharge (OR: 1.75; P = 0.04).

Conclusions: CHD is associated with altered cerebral metabolites in utero, particularly in the third trimester period of pregnancy, which is characterized by exponential brain growth and maturation, and is associated with survival to hospital discharge. The long-term neurodevelopmental consequences of these findings warrant further study.

Keywords: brain; congenital heart disease; fetus; magnetic resonance imaging; metabolites; proton magnetic resonance spectroscopy.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the National Institutes of Health Award R01HL116585 by the National Heart, Lung, and Blood Institute (primary investigator: Dr Limperopoulos) and the District of Columbia Intellectual and Developmental Disabilities Research Center Award P50HD105328 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (primary investigator: Dr Gallo). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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