Cord blood cardiovascular biomarkers in tetralogy of fallot and D-transposition of great arteries

Olga Gómez; Laura Nogué; Iris Soveral; Laura Guirado; Nora Izquierdo; Miriam Pérez-Cruz; Narcís Masoller; María Clara Escobar; Joan Sanchez-de-Toledo; Josep Maria Martínez-Crespo; Mar Bennasar; Fàtima Crispi

doi:10.3389/fped.2023.1151814

Cord blood cardiovascular biomarkers in tetralogy of fallot and D-transposition of great arteries

Front Pediatr. 2023 Apr 28:11:1151814. doi: 10.3389/fped.2023.1151814. eCollection 2023.

Authors

Olga Gómez^{1

2

3}, Laura Nogué^{1

2}, Iris Soveral^{1

4}, Laura Guirado¹, Nora Izquierdo¹, Miriam Pérez-Cruz^{1

5

6}, Narcís Masoller^{1

2}, María Clara Escobar^{5

7}, Joan Sanchez-de-Toledo^{5

7}, Josep Maria Martínez-Crespo^{1

2

3}, Mar Bennasar^{1

2}, Fàtima Crispi^{1

2

3}

Affiliations

¹ BCNatal Fetal Medicine Research Center, Sant Joan de Déu Hospital, Barcelona, Spain.
² August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
³ Fetal Medicine Department, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
⁴ Department of Obstetrics, Hospital General de Hospitalet, Barcelona, Spain.
⁵ Sant Joan de Déu Research Institute (IRSJD), Barcelona, Spain.
⁶ Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network, Carlos III Health Institute, Madrid, Spain.
⁷ Pediatric Cardiology Department, Sant Joan de Déu Hospital, Esplugues de Llobregat, Barcelona, Spain.

Abstract

Previous reports suggest that cord blood biomarkers could serve as a prognostic tool for conotruncal congenital heart defects (CHD). We aimed to describe the cord blood profile of different cardiovascular biomarkers in a prospective series of fetuses with tetralogy of Fallot (ToF) and D-transposition of great arteries (D-TGA) and to explore their correlation with fetal echocardiography and perinatal outcome.

Methods: A prospective cohort study (2014-2019), including fetuses with isolated ToF and D-TGA and healthy controls, was conducted at two tertiary referral centers for CHD in Barcelona. Obstetric ultrasound and fetal echocardiography were performed in the third trimester and cord blood was obtained at delivery. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factorβ (TGFβ), placental growth factor, and soluble fms-like tyrosine kinase-1 were determined.

Results: Thirty-four fetuses with conotruncal-CHD (22 ToF and 12 D-TGA) and 36 controls were included. ToF-fetuses showed markedly increased cord blood TGFβ (24.9 ng/ml (15.6-45.3) vs. normal heart 15.7 ng/ml (7.2-24.3) vs. D-TGA 12.6 ng/ml (8.7-37.9); P = 0.012). These results remained statistically significant even after adjusting for maternal body mass index, birth weight and mode of delivery. TGFß levels showed a negative correlation with the pulmonary valve diameter z-score at fetal echocardiography (r = -0.576, P = 0.039). No other differences were found in the rest of cord blood biomarkers among the study populations. Likewise, no other significant correlations were identified between cardiovascular biomarkers, fetal echocardiography and perinatal outcome.

Conclusions: This study newly describes increased cord blood TGFβ concentrations in ToF compared to D-TGA and normal fetuses. We also demonstrate that TGFβ levels correlate with the severity of right ventricle outflow obstruction. These novel findings open a window of research opportunities on new prognostic and potential preventive strategies.

Keywords: NT-pro-brain natriuretic peptide; Troponin I; angiogenic factors; congenital heart disease; fetal echocardiography; tetralogy of fallot; transforming growth factor beta; transposition of the great arteries.

Grants and funding

The research leading to these results has received funding from Hospital Clinic de Barcelona (Ajut Josep Font 2015 and Premi Emili Letang 2019, Barcelona, Spain), Instituto de Salud Carlos III (ISCIII) (PI15/00263, PI17/00675, PI20/00246, INT21/00027) co-funded by the European Union, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK), Fundació La Marató de TV3 (Ref 202016-30-31), and the Maternal and Child Health and Development Network (SAMID), RD16/0022/0015. Additionally, we would like to thank the Fundació Jesús Serra of the Grup Catalana Occident for the Fundació Jesús Serra Research Prize in the Clinical category awarded to the Researcher Fatima Crispi in its 4th edition for the project titled “Cardiovascular prevention from fetal life: benefits of Mediterranean diet during gestation”.