Urine metabolomic biomarkers for prediction of isolated fetal congenital heart defect

Friedman, Perry; Yılmaz, Ali; Ugur, Zafer; Jafar, Faryal; Whitten, Amy; Ustun, Ilyas; Türkoğlu, Onur; Graham, Stewart F.; Singh, Ray Bahado

doi:10.1080/14767058.2021.1914572

Cited by 14 publications

(16 citation statements)

References 39 publications

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“…However, CHD diagnosis characteristics were not defined. 33 Two studies 27,29 Analysis of identified metabolites which significantly differed between case and control groups were assessed by multivariable regression or partial least squares discriminant analysis and synthesised from variable importance in projection plots or selected through volcano plot analysis. Table S1 summarises individual metabolites distinguishing cases and controls with direction of change and method of analysis for each included study.…”

Section: Metabolic Analysis In Pregnancymentioning

confidence: 99%

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Maternal metabolomic profiling and congenital heart disease risk in offspring: A systematic review of observational studies

et al. 2023

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Aetiological understanding and screening methods for congenital heart disease (CHD) are limited. Maternal metabolomic assessment offers the potential to identify risk factors and biomarkers. We performed a systematic review (PROSPERO CRD42022308452) investigating the association between fetal/childhood CHD and endogenous maternal metabolites. Ovid‐MEDLINE, Ovid‐EMBASE and Cochrane Library were searched between inception and 06/09/2022. Case control studies included analysing maternal blood or urine metabolites in pregnancy or postpartum where there was foetal/childhood CHD. Risk of bias assessment utilised the Scottish Intercollegiate Guidelines Network methodology checklist and narrative synthesis was performed. A total of 134 records were screened with eight eligible studies (n = 3242 pregnancies, n = 842 CHD‐affected offspring). Five studies performed metabolomic analysis in pregnancy. Metabolites distinguishing case and control groups spanned lipid, glucose and amino‐acid pathways, with the development of sensitive risk prediction models. No single metabolite consistently distinguished cases and controls across studies. Three studies performed targeted analysis postnatally with altered lipid and amino acid metabolites and raised homocysteine and markers of oxidative stress identified in cases. Included studies reported small sample sizes, analysing different biosamples at variable time points using differing techniques. At present, there is not enough evidence to confidently associate maternal metabolomic profiles with offspring CHD risk. However, several identified pathways warrant further investigation.

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Section: Metabolic Analysis In Pregnancymentioning

confidence: 99%

“…Risk prediction models were developed in three studies [26][27][28] in pregnancy utilising metabolites with or without ultrasound markers.…”

Section: Risk Prediction Modelsmentioning

confidence: 99%

Maternal metabolomic profiling and congenital heart disease risk in offspring: A systematic review of observational studies

et al. 2023

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“…Metabolites 2022, 12, 100 2 of 16 This is particularly important, as disrupted metabolism related to the affected birth could impact long-term maternal health. Women with pregnancies affected by CHD have been reported with altered metabolic profiles and were associated with dysregulated metabolic pathways [7][8][9][10]. These markers were often utilized as predictive markers for fetuses with congenital heart defects.…”

Section: Congenital Heart Defects (Chds) Affect Approximately 1% Of A...mentioning

confidence: 99%

Metabolomics Signatures and Subsequent Maternal Health among Mothers with a Congenital Heart Defect-Affected Pregnancy

et al. 2022

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Congenital heart defects (CHDs) are the most prevalent and serious of all birth defects in the United States. However, little is known about the impact of CHD-affected pregnancies on subsequent maternal health. Thus, there is a need to characterize the metabolic alterations associated with CHD-affected pregnancies. Fifty-six plasma samples were identified from post-partum women who participated in the National Birth Defects Prevention Study between 1997 and 2011 and had (1) unaffected control offspring (n = 18), (2) offspring with tetralogy of Fallot (ToF, n = 22), or (3) hypoplastic left heart syndrome (HLHS, n = 16) in this pilot study. Absolute concentrations of 408 metabolites using the AbsoluteIDQ® p400 HR Kit (Biocrates) were evaluated among case and control mothers. Twenty-six samples were randomly selected from above as technical repeats. Analysis of covariance (ANCOVA) and logistic regression models were used to identify significant metabolites after controlling for the maternal age at delivery and body mass index. The receiver operating characteristic (ROC) curve and area-under-the-curve (AUC) are reported to evaluate the performance of significant metabolites. Overall, there were nine significant metabolites (p < 0.05) identified in HLHS case mothers and 30 significant metabolites in ToF case mothers. Statistically significant metabolites were further evaluated using ROC curve analyses with PC (34:1), two sphingolipids SM (31:1), SM (42:2), and PC-O (40:4) elevated in HLHS cases; while LPC (18:2), two triglycerides: TG (44:1), TG (46:2), and LPC (20:3) decreased in ToF; and cholesterol esters CE (22:6) were elevated among ToF case mothers. The metabolites identified in the study may have profound structural and functional implications involved in cellular signaling and suggest the need for postpartum dietary supplementation among women who gave birth to CHD offspring.

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“…When extending this analysis to the third trimester, by using the same tools to analyse urine samples, dysregulation was detected in lipid (including phospholipid biosynthesis, phosphatidylcholine biosynthesis, phosphatidylethanolamine biosynthesis, and fatty acid metabolism) and folate metabolism. This dysregulation in lipid metabolism may explain, at least in part, the elevated risk of CHD in offspring of diabetic mothers [ 8 ].…”

Section: Prenatal Diagnosismentioning

confidence: 99%

Metabolomics: A New Tool in Our Understanding of Congenital Heart Disease

Bassareo

McMahon

2022

Children

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Although the genetic origins underpinning congenital heart disease (CHD) have been extensively studied, genes, by themselves, do not entirely predict phenotypes, which result from the complex interplay between genes and the environment. Consequently, genes merely suggest the potential occurrence of a specific phenotype, but they cannot predict what will happen in reality. This task can be revealed by metabolomics, the most promising of the “omics sciences”. Though metabolomics applied to CHD is still in its infant phase, it has already been applied to CHD prenatal diagnosis, as well as to predict outcomes after cardiac surgery. Particular metabolomic fingerprints have been identified for some of the specific CHD subtypes. The hallmarks of CHD-related pulmonary arterial hypertension have also been discovered. This review, which is presented in a narrative format, due to the heterogeneity of the selected papers, aims to provide the readers with a synopsis of the literature on metabolomics in the CHD setting.

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Urine metabolomic biomarkers for prediction of isolated fetal congenital heart defect

Cited by 14 publications

References 39 publications

Maternal metabolomic profiling and congenital heart disease risk in offspring: A systematic review of observational studies

Maternal metabolomic profiling and congenital heart disease risk in offspring: A systematic review of observational studies

Metabolomics Signatures and Subsequent Maternal Health among Mothers with a Congenital Heart Defect-Affected Pregnancy

Metabolomics: A New Tool in Our Understanding of Congenital Heart Disease

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