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

Nickie N Andescavage, Subechhya Pradhan, Alexis C Gimovsky, Kushal Kapse, Mary T Donofrio, Jenhao Jacob Cheng, Yushuf Sharker, David Wessel, Adre J du Plessis, Catherine Limperopoulos

Journal: Journal of the American College of Cardiology 2023;82(16):1614-1623

PMID: 37821172

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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.

Address: 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.; Developing Brain Institute, Children's National Hospital, Washington, DC, USA.; Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, the George Washington University School of Medicine & Health Sciences, Washington, DC, USA.; 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.; Department of Biostatistics, Children's National Hospital, Washington, DC, USA.; 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.; 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.; 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: [email protected].

DOI: 10.1016/j.jacc.2023.08.013

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MeSH Terms: Pregnancy, Infant, Female, Humans, Transposition of Great Vessels, Magnetic Resonance Spectroscopy, Magnetic Resonance Imaging, Heart Defects, Congenital, Fetus, Brain, Lactic Acid, Choline