A prospective cohort study on association of first-trimester serum biomarkers and risk of isolated foetal congenital heart defects

Hematian, Mohammad Nasir; Hessami, Kamran; Torabi, Sara; Saleh, Maasoumeh; Nouri, Behnaz; Saleh, Mahboubeh

doi:10.1080/1354750x.2021.1994011

Cited by 2 publications

(2 citation statements)

References 19 publications

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“…Specifically, decreased PAPPA levels in the first trimester are associated with adverse pregnancy outcomes [ 22 ], while elevated serum PAPPA levels are observed in pregnant women with hypertension [ 23 ]. In addition, lower PAPPA levels and increased NT thickness in the first trimester are associated with an increased risk of CHD [ 24 ]. Our study found that PAPPA levels in GS, AF, and myocardial tissue of the CHD group were higher than those in the control group, which may be related to differences in gestational week samples across studies.…”

Section: Discussionmentioning

confidence: 99%

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

Xia,

Chen,

et al. 2023

J Transl Med

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Background Congenital heart defect (CHD) is the most common congenital abnormality, and it has long been a clinical and public health concern. Our previous findings have found Periostin (POSTN) and Pappalysin-1 (PAPPA) as potential biomarkers for fetal CHD. We aim to further elucidate POSTN's role in fetal heart development and explore the clinical applicability of POSTN and PAPPA as diagnostic marker for fetal CHD. This study is poised to establish a theoretical framework for mitigating the incidence of CHD and advance a novel approach for prenatal screening of fetal CHD. Methods We verified differential expression of POSTN and PAPPA in gravida serum and fetal amniotic fluid based on our previous research. We established the Postn knockout mouse by CRISPR/Cas9 to investigate whether Postn deletion leads to cardiac abnormalities in mice. Besides, we explored the mechanism of POSTN on heart development through Postn knockout mouse model and cell experiments. Finally, we established the logistic regression model and decision curve analysis to evaluate the clinical utility of POSTN and PAPPA in fetal CHD. Results We observed a significant decrease in POSTN and increase in PAPPA in the CHD group. Atrial septal defects occurred in Postn−/− and Postn± C57BL/6 fetal heart, while ventricular septal defects with aortic saddle were observed in Postn± C57BL/6 fetal heart. Disruption of the extracellular matrix (ECM) in cardiomyocytes and multiple abnormalities in cellular sub-organelles were observed in Postn knockout mice. POSTN may positively regulate cell behaviors and unsettle ECM via the TGFβ-Smad2/3 signaling pathway. The combination of serum biomarkers POSTN and PAPPA with Echocardiogram can enhance the diagnostic accuracy of CHD. Furthermore, the comprehensive model including POSTN, PAPPA, and two clinical indicators (NT and age) exhibits significantly higher predictive ability than the diagnosis group without the use of serum biomarkers or clinical indicators. Conclusions It is the first evidence that Postn deletion leads to cardiac developmental abnormalities in fetal mice. This may involve the regulation of the TGFβ signaling pathway. Importantly, POSTN and PAPPA possess clinical utility as noninvasive prenatal promising screening indicators of CHD.

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Section: Discussionmentioning

confidence: 99%

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

Xia,

Chen,

et al. 2023

J Transl Med

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“…Genetic metabolic studies [17] have found that a certain degree of vitamin B and folate deficiency can affect the folate synthesis pathway and lead to cardiac developmental abnormalities. HCG levels; growth-associated factors such as activin A and activin receptor-like kinase (ALK2) [18] have been associated with cardiac abnormalities, and these factors have also been shown to affect serum AFP and HCG levels [19,20]. Viruses associated with CHD such as cytomegalovirus enhancers can greatly increase the efficiency of the AFP promoter in hepatocytes, leading to a significant increase in the synthesis of AFP by hepatocytes [21].…”

Section: Discussionmentioning

confidence: 99%

Association Analysis between Maternal Serum Biomarkers and Fetal Congenital Heart Disease

Jiang,

Lin,

2023

HSF

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Objective: To investigate the association of maternal serum biomarkers alpha fetal protein (AFP), β-human chorionic gonadotropin (HCG) and unconjugated estriol 3 (uE3) in the second trimester with fetal congenital heart disease (CHD) in low risk populations during the screening of Down's syndrome. Methods: 109 cases diagnosed with fetal CHD in the second trimester by fetal echocardiography were enrolled as the CHD group. Pregnancy- and gestational-age matched 344 cases without fetal CHD were used as the control group. The values of maternal serum biomarkers HCG, AFP and uE3 were tested and the association with CHD was analyzed. Results: The means of HCG multiple of median (MoM) and AFP MoM were higher, while the mean of uE3 MoM was lower in the CHD group than those of the control group (p < 0.05). The number of cases with HCG MoM ≥85% quantile, AFP MoM ≥85% quantile was more, while that with uE3 MoM ≤15% quantile was less in the CHD group than that of the control group (p < 0.05). The univariate logistic regression analysis showed that fetal CHD was associated with high values of HCG MoM and AFP MoM and low value of uE3 MoM as well as the HCG MoM ≥85% quantile, AFP MoM ≥85% quantile and the uE3 MoM ≤15% quantile. The multivariate logistic regression analysis showed that HCG MoM ≥85% quantile and AFP MoM ≥85% quantile or the uE3 ≤15% quantile were the independent factors of fetal CHD. In addition, the risk of fetal CHD was higher when one situation existed among the HCG MoM ≥85% quantile, AFP MoM ≥85% quantile and the uE3 MoM ≤15% quantile. The risk of fetal CHD was much higher when both the HCG MoM ≥85% quantile and AFP MoM ≥85% quantile existed or both the HCG MoM ≥85% quantile and the uE3 MoM existed ≤15% quantile. Conclusions: Second trimester maternal serum biomarkers may be useful indicators for fetal evaluation for CHD to screen positive pregnancies without identified chromosomal defects.

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A prospective cohort study on association of first-trimester serum biomarkers and risk of isolated foetal congenital heart defects

Cited by 2 publications

References 19 publications

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

Association Analysis between Maternal Serum Biomarkers and Fetal Congenital Heart Disease

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