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Circulating mRNA in Maternal Plasma at the Second Trimester of Pregnancy: A Possible Screening Tool for Cardiac Conotruncal and Left Ventricular Outflow Tract Abnormalities

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Abstract

Objective

Maternal plasma is a source of circulating placental nucleic acids. This study was designed to detect aberrantly expressed placental mRNA genes circulating in the maternal plasma of pregnancies affected with fetal conotruncal anomalies (CNTRA) and left-ventricular outflow tract (LVOT) obstruction in the second trimester of pregnancy.

Methods

This was a retrospective monocentric study conducted from 1 Jan 2016 to 31 Dec 2016. NanoString technology was used to identify aberrantly expressed genes, comparing 36 women carrying a fetus with CNTRA or LVOT obstruction to 42 controls at 19–24 weeks of gestation. The genes with differential expression were subsequently tested using real-time polymerase chain reaction. Linear discriminant analysis was used to combine all the mRNA species with discriminant ability for CNTRA and LVOT obstruction. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated for the two affected groups versus controls.

Results

Three genes with differential expression, namely MAPK1, IQGAP1 and Visfatin were found. The ROC curves yielded detection rates of 60 and 62.5% at a false-positive rate of 5% for CNTRA and LVOT, respectively.

Conclusions

These data suggested that molecular screening of CNTRA and LVOT obstruction in the second trimester is feasible. Prospective studies are needed to test the discriminant ability of these genes and to calculate the predictive positive value in the general population.

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Authors and Affiliations

  1. Division of Obstetrics and Prenatal Medicine, Department of Medicine and Surgery (DIMEC) Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    Elena Contro, Diego Arcelli, Antonella Perolo, Nicola Rizzo & Antonio Farina

  2. Synlab Italia Srl, Castenedolo, Brescia, Italy

    Lara Stefani, Silvia Berto & Cristina Lapucci

  3. Pediatric Cardiology and Adult Congenital Unit, Sant’Orsola-Malpighi Hospital, Bologna, Italy

    Daniela Prandstraller

Authors
  1. Elena Contro
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  2. Lara Stefani
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  3. Silvia Berto
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  4. Cristina Lapucci
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  5. Diego Arcelli
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  6. Daniela Prandstraller
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  7. Antonella Perolo
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  8. Nicola Rizzo
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  9. Antonio Farina
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Corresponding author

Correspondence to Antonio Farina.

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Conflict of interest

E. Contro, L. Stefani, S. Berto, C. Lapucci, D. Arcelli, D. Prandstraller, A. Perolo, N. Rizzo, A. Farina declare that they have no conflict of interest.

Funding

This study was funded by RFO University of Bologna, Italy to AF and “Corsi di preparazione al parto” University of Bologna, Italy to NR.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Contro, E., Stefani, L., Berto, S. et al. Circulating mRNA in Maternal Plasma at the Second Trimester of Pregnancy: A Possible Screening Tool for Cardiac Conotruncal and Left Ventricular Outflow Tract Abnormalities. Mol Diagn Ther 21, 653–661 (2017). https://doi.org/10.1007/s40291-017-0295-7

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  • DOI: https://doi.org/10.1007/s40291-017-0295-7

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