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Cord Blood Cardiovascular Biomarkers in Left-Sided Congenital Heart Disease
Iris Soveral1,2, Laura Guirado1, Maria C Escobar-Diaz3,4
1BCNatal, Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), 08028 Barcelona, Spain.
Insights
Cord blood biomarkers can predict outcomes for fetuses with left heart defects, improving upon fetal echocardiography. Specific biomarker profiles in cord blood indicate whether a fetus will have a favorable or poor outcome.
Area of Science:
- Cardiology
- Neonatology
- Biomarkers
Background:
- Fetal echocardiography has limitations in predicting outcomes for left-sided congenital heart defects.
- Cardiovascular biomarkers in cord blood may offer improved prognostic capabilities.
Purpose of the Study:
- To investigate cord blood cardiovascular biomarker profiles in fetuses with left heart defects.
- To correlate these biomarkers with fetal outcomes (favorable vs. poor).
Main Methods:
- A multicenter prospective cohort study included fetuses with left heart defects and controls.
- Cord blood concentrations of NT-proBNP, Troponin I, TGF-β, PlGF, and sFlt-1 were measured.
- Outcomes were categorized as favorable (survival with biventricular repair) or poor (univentricular palliation, transplant, or death).
Main Results:
- Fetuses with favorable outcomes showed increased transforming growth factor β (TGF-β) and decreased placental growth factor (PlGF).
- Fetuses with poor outcomes exhibited higher N-terminal precursor of B-type natriuretic peptide (NT-proBNP) and drastically reduced soluble fms-like tyrosine kinase-1 (sFlt-1).
- A distinct cord blood biomarker profile differentiated outcomes in fetuses with left heart defects.
Conclusions:
- Cord blood biomarker profiles can predict the outcome of fetuses diagnosed with left heart defects.
- These biomarkers may enhance the prognostic evaluation beyond fetal echocardiography.
- This finding could lead to more personalized management strategies for congenital heart disease.
Abstract:
Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013−2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor β, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4−3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor β (normal heart median 15.5 ng/mL (6.8−21.4) vs. favorable outcome 51.7 ng/mL (13.8−73.9) vs. poor outcome 25.1 ng/mL (6.9−39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8−23.9) vs. favorable outcome 12.8 pg/mL (11.7−13.6) vs. poor outcome 11.0 pg/mL (8.8−15.4), p < 0.001). Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide (normal heart 508.0 pg/mL (287.5−776.3) vs. favorable outcome 617.0 pg/mL (389.8−1087.8) vs. poor outcome 1450.0 pg/mL (919.0−1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3−2715.8) vs. favorable outcome (1848.3 pg/mL (646.9−2313.6) vs. poor outcome 259.0 pg/mL (182.0−606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome.
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