Key result
Complex congenital heart disease linked to lower fetal cerebral NAA:choline ratios vs healthy controls.
Why the study?
Does complex congenital heart disease alter fetal cerebral biochemical metabolite profiles measured by proton magnetic resonance spectroscopy and associate with infant survival to discharge compared with healthy control fetuses?
Cohort (n=333)
Single-blind (data underwent visual inspection by a single investigator blinded to case status)
No
Does complex congenital heart disease alter fetal cerebral biochemical metabolite profiles measured by proton magnetic resonance spectroscopy and associate with infant survival to discharge compared with healthy control fetuses?
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Over the past decade, our team has been at the forefront of developing safe and sophisticated ways to measure and monitor fetal brain health in the womb. By tapping into the power of advanced imaging, we were able to measure certain maturational components of the brain to find early biomarkers for newborns who are going to struggle immediately after birth.”
“With important clues about how a fetus is growing and developing, we can provide better care to help these children not only survive, but thrive, in the newborn period and beyond.”
“For many years we have known that the brains of children with severe heart problems do not always develop normally, but new research shows that abnormal function occurs already in the fetus. Understanding how the development and function of the brain is already different before a baby with a heart defect is born will help us to intervene with personal treatment as early as possible, perhaps even prenatally, and improve outcomes.”
In utero cerebral metabolic disturbances in fetuses with complex congenital heart disease emerge specifically during the third trimester of rapid brain growth, and elevated fetal cerebral lactate predicts mortality prior to hospital discharge.
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.
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Andescavage et al. (2023) conducted a cohort in Fetal complex congenital heart disease (n=333). Complex congenital heart disease (evaluated via fetal cerebral proton magnetic resonance spectroscopy) vs. Healthy fetuses from uncomplicated pregnancies with normal prenatal screening was evaluated on Fetal cerebral N-acetyl aspartate to choline (NAA:Cho) ratio (p=0.001). Fetuses with complex congenital heart disease had lower cerebral N-acetyl aspartate:choline ratios and higher choline levels than healthy controls.
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