title: Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center.
abstract: OBJECTIVE
  To review the performance of non-invasive prenatal testing (NIPT) by low-coverage whole-genome sequencing of maternal plasma DNA at a single center.
  
  
  METHODS
  The NIPT result and pregnancy outcome of 1982 consecutive cases were reviewed. NIPT was based on low coverage (0.1×) whole-genome sequencing of maternal plasma DNA. All subjects were contacted for pregnancy and fetal outcome.
  
  
  RESULTS
  Of the 1982 NIPT tests, a repeat blood sample was required in 23 (1.16%). In one case, a conclusive report could not be issued, probably because of an abnormal vanished twin fetus. NIPT was positive for common trisomies in 29 cases (23 were trisomy 21, four were trisomy 18 and two were trisomy 13); all were confirmed by prenatal karyotyping (specificity=100%). In addition, 11 cases were positive for sex-chromosomal abnormalities (SCA), and nine cases were positive for other aneuploidies or deletion/duplication. Fourteen of these 20 subjects agreed to undergo further investigations, and the abnormality was found to be of fetal origin in seven, confined placental mosaicism (CPM) in four, of maternal origin in two and not confirmed in one. Overall, 85.7% of the NIPT-suspected SCA were of fetal origin, and 66.7% of the other abnormalities were caused by CPM. Two of the six cases suspected or confirmed to have CPM were complicated by early-onset growth restriction requiring delivery before 34 weeks. Fetal outcome of the NIPT-negative cases was ascertained in 1645 (85.15%). Three chromosomal abnormalities were not detected by NIPT, including one case each of a balanced translocation, unbalanced translocation and triploidy. There were no known false negatives involving the common trisomies (sensitivity=100%).
  
  
  CONCLUSIONS
  Low-coverage whole-genome sequencing of maternal plasma DNA was highly accurate in detecting common trisomies. It also enabled the detection of other aneuploidies and structural chromosomal abnormalities with high positive predictive value.
authors: Fetal Medicine Centre, Paramount Medical Centre, Hong Kong, China.
authors: T K
authors: TK
authors: Lau
authors: S W
authors: SW
authors: Cheung
authors: P S S
authors: PS
authors: Lo
authors: A N
authors: AN
authors: Pursley
authors: M K
authors: MK
authors: Chan
authors: F
authors: F
authors: Jiang
authors: H
authors: H
authors: Zhang
authors: W
authors: W
authors: Wang
authors: L F J
authors: LF
authors: Jong
authors: O K C
authors: OK
authors: Yuen
authors: H Y C
authors: HY
authors: Chan
authors: W S K
authors: WS
authors: Chan
authors: K W
authors: KW
authors: Choy
mesh_terms: D025063:Chromosome Disorders / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D008423:Maternal Age; D009035:Mothers; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
chemical_list: D005819:Genetic Markers; D004247:DNA
keywords: NIPT; aneuploidy; chromosomal deletions; chromosomal duplications; fetal DNA; next-generation sequencing; sex chromosomal abnormality; whole genome