Gómez Olga, Nogué Laura, Soveral Iris, Guirado Laura, Izquierdo Nora, Pérez-Cruz Miriam, Masoller Narcís, Escobar María Clara, Sanchez-de-Toledo Joan, Martínez-Crespo Josep Maria, Bennasar Mar, Crispi Fàtima
BCNatal Fetal Medicine Research Center, Sant Joan de Déu Hospital, Barcelona, Spain.
August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Front Pediatr. 2023 Apr 28;11:1151814. doi: 10.3389/fped.2023.1151814. eCollection 2023.
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.
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.
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); = 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 -score at fetal echocardiography ( = -0.576, = 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.
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.
先前的报告表明,脐血生物标志物可作为圆锥动脉干先天性心脏病(CHD)的预后工具。我们旨在描述法洛四联症(ToF)和大动脉转位(D-TGA)胎儿前瞻性系列研究中不同心血管生物标志物的脐血特征,并探讨它们与胎儿超声心动图及围产期结局的相关性。
在巴塞罗那的两个先天性心脏病三级转诊中心进行了一项前瞻性队列研究(2014 - 2019年),纳入孤立性ToF和D-TGA胎儿以及健康对照。在孕晚期进行产科超声和胎儿超声心动图检查,并在分娩时采集脐血。测定脐血中B型利钠肽N端前体、肌钙蛋白I、转化生长因子β(TGFβ)、胎盘生长因子和可溶性fms样酪氨酸激酶-1的浓度。
纳入34例圆锥动脉干型先天性心脏病胎儿(22例ToF和12例D-TGA)及36例对照。ToF胎儿脐血TGFβ明显升高(24.9 ng/ml(15.6 - 45.3),正常心脏为15.7 ng/ml(7.2 - 24.3),D-TGA为12.6 ng/ml(8.7 - 37.9);P = 0.012)。即使在调整孕妇体重指数、出生体重和分娩方式后,这些结果仍具有统计学意义。TGFβ水平与胎儿超声心动图中肺动脉瓣直径评分呈负相关(r = -0.576,P = 0.039)。在研究人群的其他脐血生物标志物中未发现其他差异。同样,在心血管生物标志物、胎儿超声心动图和围产期结局之间未发现其他显著相关性。
本研究首次描述了与D-TGA和正常胎儿相比,ToF胎儿脐血TGFβ浓度升高。我们还证明TGFβ水平与右心室流出道梗阻的严重程度相关。这些新发现为新的预后和潜在预防策略打开了研究机会之窗。