Noninvasive prenatal screening for fetal common sex chromosome aneuploidies from maternal blood

Abstract

ObjectiveTo explore the feasibility of high-throughput massively parallel genomic DNA sequencing technology for the noninvasive prenatal detection of fetal sex chromosome aneuploidies (SCAs).MethodsThe study enrolled pregnant women who were prepared to undergo noninvasive prenatal testing (NIPT) in the second trimester. Cell-free fetal DNA (cffDNA) was extracted from the mother’s peripheral venous blood and a high-throughput sequencing procedure was undertaken. Patients identified as having pregnancies associated with SCAs were offered prenatal fetal chromosomal karyotyping.ResultsThe study enrolled 10 275 pregnant women who were prepared to undergo NIPT. Of these, 57 pregnant women (0.55%) showed fetal SCA, including 27 with Turner syndrome (45,X), eight with Triple X syndrome (47,XXX), 12 with Klinefelter syndrome (47,XXY) and three with 47,XYY. Thirty-three pregnant women agreed to undergo fetal karyotyping and 18 had results consistent with NIPT, while 15 patients received a normal karyotype result. The overall positive predictive value of NIPT for detecting SCAs was 54.54% (18/33) and for detecting Turner syndrome (45,X) was 29.41% (5/17).ConclusionNIPT can be used to identify fetal SCAs by analysing cffDNA using massively parallel genomic sequencing, although the accuracy needs to be improved particularly for Turner syndrome (45,X).

High false‐positive non‐invasive prenatal screening results for sex chromosome abnormalities: Are maternal factors the culprit?

“…In several large prospective studies, the specificity of NIPS for SCAs detection was consistently low, leading to relatively higher false‐positive rates . Previously, we demonstrated that the overall predictive positive rate of NIPS for SCAs was 54.54% . In 2016, the international guidelines issued by the American College of Obstetricians and Gynaecologists (ACOG) claimed that the false‐positive rate of SCAs by NIPS was approximately 1% …”

Pregnancy outcome of autosomal aneuploidies other than common trisomies detected by noninvasive prenatal testing in routine clinical practice

“…Noninvasive prenatal testing has been recommended as a first‐tier or second‐tier screening test for fetal common trisomies, with lower false‐positive rates and higher positive predictive values than serum biochemical screening . Noninvasive prenatal testing can also enable the detection of other aneuploidies, including sex chromosome aneuploidies (SCA) and structural chromosomal abnormalities . However, most of the published data have mainly focused on 3 common aneuploidies, SCA, and subchromosomal deletions/duplications.…”

PREFACE: In silico pipeline for accurate cell‐free fetal DNA fraction prediction

“…Gonosomal aberrations are theoretically exposed during NIPT in a similar way as any other aneuploidy. Nevertheless, the specificity is reported to be much lower in comparison with traditional screening of chromosomes 13, 18, and 21, especially for monosomy X . Ethical issues on reporting these sometimes nonsevere abnormalities aside, the incorporation of FF in statistical outcome—which is generally not done with, eg, the popular z ‐score approach—does improve performance .…”