Non-invasive prenatal testing by using next-generation sequencing of cell-free DNA from maternal plasma in multifetal pregnancies

Abstract

Objective The objective of this study is to evaluate the performance of non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 by using next-generation sequencing of cell-free DNA from maternal plasma in multifetal pregnancies.

Method A double-blind prospective study was performed from 2014 November to 2015 June. Among a cohort of 211 high-risk pregnancies, 23 multifetal pregnant women who were expected to undergo invasive procedures for fetal karyotype diagnosis, were recruited. At same time, invasive procedures and maternal plasma DNA sequencing were performed to detect trisomies 21 ,18 and 13. For each target chromosome 21, 18, 13 z-scores of 3 or higher were classified with trisomy high risk and z-scores of 2 over less than 3 were classified with trisomy potential high risk. The fetal karyotype of invasive test was used as gold standard to confirm the detection rate, false negative and false positive of sequencing-based non-invasive prenatal test.

Results There were 3 monochorionic diamniotic (MCDA) twins, 19 dichorionic diamniotic (DCDA) twins and 1 trichorionic triamniotic (TCTA) triplets. There were two discordant twins of trisomy 21 confirmed by karyotyping. Plasma DNA sequencing correctly identified two cases of trisomy 21. The maternal plasma DNA sequencing for fetal trisomy 21 showed 100% accurate detection respectively.

Conclusion Although study size is limited, this study showed that NIPT could be applicable to multifetal pregnancies with accurate detection and further supported that sequencing-based NIPT of trisomy 21 in multifetal pregnancies could be achieved with a high accurate efficiency, which could effectively avoid invasive prenatal diagnosis procedures.