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

Nickie N. Andescavage, Department of Neonatology, Children's National Hospital, Washington, DC, USA; Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, the George Washington University School of Medicine & Health Sciences, Washington, DC, USA.
Subechhya Pradhan, Developing Brain Institute, Children's National Hospital, Washington, DC, USA.
Alexis C. Gimovsky, Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, the George Washington University School of Medicine & Health Sciences, Washington, DC, USA.
Kushal Kapse, Developing Brain Institute, Children's National Hospital, Washington, DC, USA.
Mary T. Donofrio, Department of Pediatrics, the George Washington University School of Medicine & Health Sciences, Washington, DC, USA; Department of Cardiology, Children's National Hospital, Washington, DC, USA.
Jenhao Jacob Cheng, Department of Biostatistics, Children's National Hospital, Washington, DC, USA.
Yushuf Sharker, Developing Brain Institute, Children's National Hospital, Washington, DC, USA.
David Wessel, Department of Pediatrics, the George Washington University School of Medicine & Health Sciences, Washington, DC, USA; Department of Critical Care Medicine, Children's National Hospital, Washington, DC, USA.
Adre J. du Plessis, Department of Pediatrics, the George Washington University School of Medicine & Health Sciences, Washington, DC, USA; Prenatal Pediatric Institute, Children's National Hospital, Washington, DC, USA.
Catherine Limperopoulos, Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, the George Washington University School of Medicine & Health Sciences, Washington, DC, USA; Department of Radiology, Children's National Hospital, Washington, DC, USA; Department of Radiology, the George Washington University School of Medicine & Health Sciences, Washington, DC, USA. Electronic address: climpero@childrensnational.org.

Document Type

Journal Article

Publication Date

10-17-2023

Journal

Journal of the American College of Cardiology

Volume

82

Issue

16

DOI

10.1016/j.jacc.2023.08.013

Keywords

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

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.

Department

Pediatrics

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