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Review
. 2014 Jan;60(1):78-87.
doi: 10.1373/clinchem.2013.202663. Epub 2013 Nov 19.

Integration of noninvasive DNA testing for aneuploidy into prenatal care: what has happened since the rubber met the road?

Diana W Bianchi  1 , Louise Wilkins-Haug
Affiliations
Review

Integration of noninvasive DNA testing for aneuploidy into prenatal care: what has happened since the rubber met the road?

Diana W Bianchi et al. Clin Chem. 2014 Jan.

Abstract

Background: Over the past 2 years, noninvasive prenatal testing (NIPT), which uses massively parallel sequencing to align and count DNA fragments floating in the plasma of pregnant women, has become integrated into prenatal care. Professional societies currently recommend offering NIPT as an advanced screen to pregnant women at high risk for fetal aneuploidy, reserving invasive diagnostic procedures for those at the very highest risk.

Content: In this review, we summarize the available information on autosomal and sex chromosome aneuploidy detection. Clinical performance in CLIA-certified, College of American Pathology-accredited laboratories appears to be equivalent to prior clinical validation studies, with high sensitivities and specificities and very high negative predictive values. The main impact on clinical care has been a reduction in invasive procedures. Test accuracy is affected by the fetal fraction, the percentage of fetal DNA in the total amount of circulating cell-free DNA. Fetal fraction is in turn affected by maternal body mass index, gestational age, type of aneuploidy, singleton vs multiples, and mosaicism. Three studies comparing NIPT to serum or combined screening for autosomal aneuploidy all show that NIPT has significantly lower false-positive rates (approximately 0.1%), even in all-risk populations. A significant number of the discordant positive cases have underlying biological reasons, including confined placental mosaicism, maternal mosaicism, cotwin demise, or maternal malignancy.

Summary: NIPT performs well as an advanced screen for whole chromosome aneuploidy. Economic considerations will likely dictate whether its use can be expanded to all risk populations and whether it can be applied routinely for the detection of subchromosome abnormalities.

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Conflict of interest statement

Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:

Employment or Leadership: D.W. Bianchi, Verinata Health, an Illumina company.

Consultant or Advisory Role: D.W. Bianchi, Verinata Health.

Stock Ownership: None declared.

Honoraria: D.W. Bianchi, Verinata Health.

Research Funding: L.E. Wilkins-Haug, Arisoa, Sequenom–Women and Infants Hospital.

Expert Testimony: None declared.

Patents: None declared.

Figures

Fig. 1
Fig. 1
Major differences in the technical approaches to sequencing of circulating cell-free DNA in the plasma of pregnant women.
See this image and copyright information in PMC

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