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. 2022 Nov 30;11(23):7119.
doi: 10.3390/jcm11237119.

Cord Blood Cardiovascular Biomarkers in Left-Sided Congenital Heart Disease

Iris Soveral  1   2 , Laura Guirado  1 , Maria C Escobar-Diaz  3   4 , María José Alcaide  5   6 , Josep Maria Martínez  1   7   8   9 , Víctor Rodríguez-Sureda  1   9 , Bart Bijnens  8   10 , Eugenia Antolin  6   11 , Elisa Llurba  12   13 , Jose L Bartha  6   11 , Olga Gómez  1   7   8   9 , Fàtima Crispi  1   7   8   9
Affiliations

Cord Blood Cardiovascular Biomarkers in Left-Sided Congenital Heart Disease

Iris Soveral et al. J Clin Med. .

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.

Keywords: B-type natriuretic peptide; angiogenic factors; aortic coarctation; aortic stenosis; congenital heart defects; fetal cardiac remodeling; fetal echocardiography; hypoplastic left heart syndrome; transforming growth factor beta.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flowchart of fetuses with left-side congenital heart defects included in the study.
Figure 2
Figure 2
Concentrations of N-terminal precursor of B-type natriuretic peptide (NT-Pro-BNP), Troponin I, transforming growth factor β (TGFβ), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt1) in the cord blood of fetuses with normal heart and with favorable and poor outcome left congenital heart defects. Poor cardiac outcome is defined as univentricular circulation, heart transplant, or death. p-values are shown for significantly different (p < 0.05) comparisons.
Figure 3
Figure 3
(a) Concentrations of soluble fms-like tyrosine kinase-1 (sFlt1) in the cord blood of control fetuses and fetuses with expected biventricular repair, classified according to outcome (red triangle, favorable outcome; black star, poor outcome. Reference line set at 1520.7 pg/mL identified at (b) ROC curve for sFlt1 as a predictor of favorable outcome in fetuses with expected biventricular outcome.
See this image and copyright information in PMC

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