To determine the underlying biological basis for noninvasive prenatal testing (NIPT) results of multiple aneuploidies or autosomal monosomies.
Retrospective analysis of 113,415 tests to determine the study cohort, consisting of 138 (0.12%) cases reported as a single autosomal monosomy (n = 65), single trisomy with a sex chromosome aneuploidy (n = 36), or with multiple aneuploidies (n = 37). Clinical outcome information was reviewed and stratified into eight categories according to whether the karyotype or sonographic information agreed or disagreed with sequencing results.
Of 67 cases with fetal or neonatal karyotypes available, 16 (24%) were partially or fully concordant with the NIPT result, 4 (6%) had aneuploidy on a reference chromosome, and 47 (70%) had normal fetal chromosomes, in which 5/47 had maternal malignancies reported. One case of maternal mosaic trisomy 8 was also detected. Of cases with no fetal karyotype information, ten had an abnormal clinical outcome, one was a normal live birth, and one reported maternal malignancy.
Noninvasive prenatal test results of autosomal monosomy or multiple aneuploidies are rare but have a diversity of underlying biologic causes. Some reflect the fetal karyotype; some reflect the presence of other maternal or fetal chromosome abnormalities, and a small number are linked to maternal disease. © 2016 Illumina. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
What's already known about this topic?
Noninvasive prenatal testing (NIPT) has been validated for common autosomal trisomies (trisomy 21, 18, and 13), sex chromosome aneuploidies, and a selection of microdeletion syndromes.NIPT findings that are discordant with the fetal karyotype can be because of biological reasons, such as confined placental mosaicism, maternal chromosome abnormalities, and other maternal conditions such as occult malignancy.
What does this study add?
Clinical and karyotype outcome information for cases that received an NIPT result indicating an autosomal monosomy or multiple aneuploidies. Some autosomal monosomy and multiple aneuploidy results reflect the true fetal karyotype, and some are explained by other factors, such as other fetal or maternal chromosomal abnormalities or maternal disease.This information will help providers with post‐test counseling for these rare and unusual results.