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Observational Study
. 2015 Feb;125(2):375-382.
doi: 10.1097/AOG.0000000000000637.

Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical laboratory experience and biology

Diana W Bianchi  1 , Saba Parsa, Sucheta Bhatt, Meredith Halks-Miller, Kathryn Kurtzman, Amy J Sehnert, Amy Swanson
Affiliations
Observational Study

Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical laboratory experience and biology

Diana W Bianchi et al. Obstet Gynecol. 2015 Feb.

Abstract

Objective: To describe the clinical experience with noninvasive prenatal testing for fetal sex chromosomes using sequencing of maternal plasma cell-free DNA in a commercial laboratory.

Methods: A noninvasive prenatal testing laboratory data set was examined for samples in which fetal sex chromosomes were reported. Available clinical outcomes were reviewed.

Results: Of 18,161 samples with sex chromosome results, no sex chromosome aneuploidy was detected in 98.9% and the fetal sex was reported as XY (9,236) or XX (8,721). In 4 of 32 cases in which the fetal sex was reportedly discordant between noninvasive prenatal testing and karyotype or ultrasonogram, a potential biological reason for the discordance exists, including two cases of documented co-twin demise, one case of a maternal kidney transplant from a male donor, and one case of fetal ambiguous genitalia. In the remaining 204 samples (1.1%), one of four sex chromosome aneuploidies (monosomy X, XXX, XXY, or XYY) was detected. The frequency of false positive results for sex chromosome aneuploidies is a minimum of 0.26% and a maximum of 1.05%. All but one of the discordant sex chromosome aneuploidy results involved the X chromosome. In two putative false-positive XXX cases, maternal XXX was confirmed by karyotype. For the false-positive cases, mean maternal age was significantly higher in monosomy X (P<.001) and lower in XXX (P=.008).

Conclusion: Noninvasive prenatal testing results for sex chromosome aneuploidy can be confounded by maternal or fetal biological phenomena. When a discordant noninvasive prenatal testing result is encountered, resolution requires additional maternal history, detailed fetal ultrasonography, and determination of fetal and possibly maternal karyotypes.

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References

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