Potential role of maternal serum microRNAs as a biomarker for fetal congenital heart defects
Introduction
Congenital heart defects (CHD), which include malformations of the heart or great vessels, are the most common group of major birth defects with an incidence of 5–8/1000 live births [1]. The incidence of CHD is 6 times more common than chromosomal abnormalities and 4 times more common than neural tube defects [2]. CHD accounts for approximately 40% of perinatal deaths, and more than 20% of deaths in the first month of life [3]. Approximately half of the cases of CHD are severe and usually require one or more surgical procedures in the neonatal period or during childhood [4]. These defects therefore place a significant economic burden on the National Health Service and society in general, as well as the psychological wellbeing of affected children and families.
Interdisciplinary collaboration between neonatology, obstetric and prenatal medicine, pediatric cardiology, and pediatric cardiac surgery is essential to improve the perinatal treatment of neonates with CHD. If a heart defect has already been diagnosed prenatally, arrangements can be made for the child to be born in the relevant perinatal or cardiac pediatric center. This enables them to receive treatment without delay in the affiliated departments, avoiding a potentially hazardous postnatal transportation or inadequate perinatal care [5]. In many cases, early interventional and/or surgical treatment is important to improve the prognosis of neonates with CHD besides using intensive care and medication. Therefore, it is important to screen and identify neonates with critical CHD in order to reduce morbidity and mortality by enabling proactive medical treatment. At the same time, early knowledge of CHD also allows for further monitoring, testing for associated non-cardiac structural and chromosomal anomalies and parental counseling with regards to pregnancy management options, including termination [6].
Section snippets
Prenatal screening fetal CHD by ultrasound examination
Fetal echocardiography has been used as a screening tool for CHD. Rasiah et al. conducted a systematic review to evaluate the accuracy of ultrasound examination in detecting fetal CHD [7]. The pooled sensitivity and specificity for ultrasound screening fetal CHD were 85% (95% CI, 78–90%) and 99% (95% CI, 98–100%), respectively. However, at present, the use of ultrasound examination in detecting major CHD are limited to a few specialized and experienced centers where it may be offered to
Biomarkers for fetal CHD screening
Biomarkers are defined as any substance, structure or process that can be measured in the body, or its products, which can influence or predict the incidence of a specific disease. We hypothesize that combining biomarkers with fetal echocardiography could improve the accuracy of fetal CHD screening.
Various biomarkers for fetal CHD are currently available. The measurement of nuchal translucency (NT) is widely used as a marker for screening for CHD [12]. In a meta-analysis, NT as a screening test
The hypothesis
High-throughput approaches, including next-generation sequencing and microarrays, have been used for candidate biomarker selection and identification in many diseases [17]. The identification of biomarkers for CHD is in progress and some positive results have been obtained [18]. MicroRNAs (miRNAs) that contribute to cardiac development have been found, and these could be used as novel biomarkers and therapeutic targets for CHD [19]. Ongoing studies are screening the expression profiles of
Serum miRNAs: promising novel biomarkers for clinical diseases
MiRNAs are a recently discovered class of small non-coding RNAs that regulate gene expression and have a critical role in many biological and pathological processes. miRNAs are short (19–25 nucleotides), single-stranded, and non-protein-coding RNAs that regulate gene expression by binding to the three prime untranslated region (3′ UTR) of the target mRNA. They have functions in diverse biological processes, including development, differentiation, apoptosis, and oncogenesis [21]. Recent studies
Research implications for maternal serum miRNAs as a biomarker for fetal CHD
The discovery of fetal miRNAs in the plasma of pregnant women has led to the development of a number of noninvasive prenatal diagnostic tests. Circulating fetal miRNA in maternal plasma has been demonstrated to be useful for prenatal investigations of fetal diseases. At present, certain specific miRNAs of cardiogenesis have been identified [31]; these studies have shown that miRNAs of placental origin can be detected in peripheral blood drawn from pregnant women [20], and some data have even
Conclusion
Fetal echocardiography has been used as the principal screening tool to identify CHD prenatally, but the dependency of ultrasound examination on the skills and experience of the operator is a major pitfall. Since early identification of the presence of a CHD may give a survival advantage to the affected infant, it is reasonable to postulate the importance of the identification of biomarkers that enable the early, accurate and operator-independent screening of fetal CHD. Various biomarkers for
Conflict of interest
None declared.
Acknowledgment
This work was supported by a grant from the National Natural Science Foundation of China (Nos. 30973213 and 81070500).
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Cited by (29)
Molecular systems in cardiovascular developmental disorders
2019, Clinical Molecular Medicine: Principles and PracticeExpression profile of maternal circulating microRNAs as non-invasive biomarkers for prenatal diagnosis of congenital heart defects
2019, Biomedicine and PharmacotherapyCitation Excerpt :Additionally, it has been found that miR-19a expression is enhanced in the plasma of pulmonary arterial hypertension patients, suggesting that miR-19a may be a biomarker for the diagnosis of pulmonary arterial hypertension [20]. The hypothesis that maternal serum miRNAs can serve as potential biomarkers for CHDs has been supported by the findings of Yu et al. [21]. However, only one study has thus far focused on the maternal circulating miRNA expression profile in fetal CHDs: Zhu et al. [22] showed that the expression of four miRNA (miR-19b, miR-22, miR-29c, and miR-375) is up-regulated in maternal serum of pregnant women with fetal CHDs, including VSD, ASD and TOF, at gestational ages of 24.99 ± 1.29 weeks.
Potential role of blood microRNAs as non-invasive biomarkers for early detection of asymptomatic coronary atherosclerosis in obese children with metabolic syndrome
2012, Medical HypothesesCitation Excerpt :MiRNAs has gained a growing interest in the last few years to be used as a stable biomarker for disease diagnosis [13]. Very recently, miRNAs hypothesized to serve as potential biomarkers for many diseases including congenital heart disease (CHD) [14], non-hypertensive intracerebral hemorrhage [15], Alzheimer’s disease [16] and peritoneal fibrosis [17]. Recent studies indicates that several circulating miRNAs are dysregulated in the plasma of coronary artery disease (CAD) patients, most of them known to be expressed in the vascular wall, particularity in the endothelial cells [18,19].
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2013, Journal of Developmental Origins of Health and DiseaseMicroRNAs: A new piece in the paediatric cardiovascular disease puzzle
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