Noninvasive Analysis of Mother's Blood Detects Fetal Chromosomal Abnormalities

While chromosomal aneuploidies represent a major cause of fetal loss and birth defects, current methods for the prenatal diagnosis of aneuploidy require invasive methods that are associated with a risk of miscarriage and other complications.

A recently developed technique, massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma, avoids the risk of fetal loss associated with more invasive diagnostic procedures.

Investigators at the University of California, San Diego (USA) employed an Ion Torrent sequencer, a benchtop semiconductor sequencing platform (SSP) developed by Life Technologies (Carlsbad, CA, USA), to perform MPS analysis on plasma samples from 2,275 pregnant subjects. Life Technologies is a member of the Thermo Fisher Scientific (Milford, MA, USA) family of companies.

The pool of 2,275 subjects contained a group of 515 women who had full karyotyping results and were used for retrospective analysis. The remaining 1,760 subjects without karyotyping were analyzed in a prospective study.

In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and three trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected.

“To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using SSP,” said senior author Dr. Kang Zhang, professor of ophthalmology at the University of California, San Diego. “It provides an effective strategy for large-scale, noninvasive screenings in a clinical setting. It can be done in hospitals and outpatient clinics, more quickly and cheaply. We believe this approach could become the standard of care for screening of prenatal chromosomal abnormalities.”

The SSP study was published in the May 5, 2014, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Related Links:
University of California, San Diego
Life Technologies
Thermo Fisher Scientific