Abstract:

Objective To investigate the application role of expanded non-invasive prenatal testing（NIPT-plus） in the determination of chromosome copy number variation（microdeletion or microduplication）. Methods A total of 10 187 pregnant women who underwent NIPT-plus were enrolled from the Genetics Center of Gansu Maternal and Child Health Hospital form 2017 to 2018. NIPT-plus was used to determine cell-free fetal DNA（cffDNA） in the plasma of pregnant women. The high-risk pregnant women in NIPT-plus were diagnosed by amniotic fluid karyotyping and copy number variation sequencing（CNV-seq） and were followed up until fetal induction or 3 months after birth. Results Among the 10 187 pregnant women，164 high-risk pregnant women were screened，of which 131 cases were at high risk for chromosome aneuploidy，and 33 cases were at high risk for chromosome microdeletion or microduplication. Totally，131 cases of 164 high-risk pregnant women received CNV-seq，and 59 positive cases were confirmed，including 46 cases of chromosome aneuploidy，13 cases of chromosome microdeletion or microduplication and 72 cases of false positivity. The positive predictive value，sensitivity and specificity of 5-10 Mb deletion or duplication for NIPT-plus were 100.00%. The positive predictive value，sensitivity and specificity of >10 Mb deletion or duplication were 62.50%，100.00% and 99.97%，respectively. The positive predictive value，sensitivity and specificity of <5 Mb deletion or duplication were 42.86%，90.00% and 99.88%，respectively. Conclusions The determination rate of NIPT-plus for chromosome deletion or duplication ≥5 Mb is high，and the positive predictive value for chromosome microdeletion or microduplication <5 Mb is low. The performance of NIPT-plus in chromosome microdeletion or microduplication should be further improved.

Key words: Expanded non-invasive prenatal testing, Chromosome copy number variation, Copy number variation sequencing