Elsevier

Medical Hypotheses

Volume 76, Issue 3, March 2011, Pages 424-426
Medical Hypotheses

Potential role of maternal serum microRNAs as a biomarker for fetal congenital heart defects

https://doi.org/10.1016/j.mehy.2010.11.010Get rights and content

Abstract

Congenital heart defects (CHD) are the most common form of major birth defect, affecting almost 1% of live births. These defects place a significant economic burden on the National Health Service and on the psychological wellbeing of affected families. The early screening and identification of neonates with CHD could reduce morbidity and mortality by allowing proactive medical treatment and parental counseling about options during pregnancy, including termination. Fetal echocardiography is the principal screening tool for the identification of CHD, but its accuracy mainly depends on the skill and experience of the operator. Various biomarkers of screening for fetal CHD are currently available, such as nuchal translucency (NT), β-hCG and PAPP-A; however, these are non-specific indexes with high incidences of false positive results. Certain specific microRNAs (miRNAs) of cardiogenesis have been identified, which correlate positively with placental miRNA expression. These miRNAs of placental origin can be detected in maternal peripheral blood. Therefore, we postulate that these maternal serum miRNAs may be a potential biomarker for fetal CHD.

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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