Key result
Untargeted metabolomics of amniotic fluid revealed no significant overall metabolic profile differences across congenital heart disease severities, though specific metabolites like sorbose and gluconolactone correlated with moderate and severe lesions.
Why the study?
Differences in metabolic profiles associated with congenital heart disease of varying severity have not been elucidated.
Observational (n=51)
No
Specific amniotic fluid metabolites, such as gluconolactone and ornithine, differ significantly among fetuses with mild, moderate, and severe congenital heart disease, providing potential insights into the pathological mechanisms of CHD severity.
Severity-specific amniotic fluid metabolites in fetal CHD are hypothesis-generating; validation studies needed before mechanistic or clinical inferences.
Background Congenital heart disease (CHD) is characterized by various phenotypes, however, differences in metabolic profiles associated with CHD of various severity have not been elucidated. In this study, differences in metabolite concentrations among mild, moderate, and severe forms of CHD were explored, providing novel clues for our understanding of the mechanism of CHD. Methods Maternal amniotic fluid samples from fetuses with mild (n = 15), moderate (n = 7), and severe (n = 29) CHD lesions were analyzed by GC-TOF/MS. PCA, PLS-DA, and differential metabolite analysis among these three groups were conducted. Results PCA and PLS-DA models showed that metabolic profiles were comparable among CHD of different severity. Significant differences between mild and moderate CHD lesions were observed in the levels of gluconolactone, ornithine, threonine, sorbose, pentadecanoic acid, and the uric acid/xanthine ratio. Of these six differential metabolites, gluconolactone (r = 0.469, P = 0.028), sorbose (r = 0.577, P = 0.005) and the uric acid/xanthine ratio (r = 0.438, P = 0.041) were positively correlated with moderate CHD lesions, while ornithine (r=-0.531, P = 0.011), threonine (r=-0.546, P = 0.009), and pentadecanoic acid (r=-0.454, P = 0.034) were negatively associated. We found 9 differential metabolites between mild and severe CHD lesions, among which the alpha-ketoisovaleric acid/valine ratio (r=-0.383, P = 0.010), gluconolactone (r = 0.391, P = 0.009), and 4-hydroxycinnamic acid (r = 0.342, P = 0.023) were correlated with severe CHD lesions. Only sorbose showed significant differences between moderate and severe CHD lesions, and was negatively associated with severe CHD lesions (r=-0.341, P = 0.042). Conclusions Compared with mild CHD, specific differences were observed in metabolites or metabolite ratios in moderate and severe CHD lesions of CHD, several of which were significantly correlated with CHD severity. These results can help to understand the metabolic status of the affected fetus and provide new possibilities for exploring the pathological mechanism of CHD.
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Li et al. (2023) conducted an observational in Congenital heart disease (n=51). Moderate or severe congenital heart disease vs. Mild congenital heart disease was evaluated on Differences in amniotic fluid metabolite concentrations. Untargeted metabolomics of amniotic fluid revealed no significant overall metabolic profile differences across congenital heart disease severities, though specific metabolites like sorbose and gluconolactone correlated with moderate and severe lesions.
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