Massively parallel sequencing of maternal plasma DNA in 113 cases of fetal nuchal cystic hygroma

Obstet Gynecol. 2013 May;121(5):1057-1062. doi: 10.1097/AOG.0b013e31828ba3d8.


Objective: To estimate the accuracy and potential clinical effect of using massively parallel sequencing of maternal plasma DNA to detect fetal aneuploidy in a cohort of pregnant women carrying fetuses with nuchal cystic hygroma.

Methods: The MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) study database was queried to identify eligible patients carrying fetuses with cystic hygroma (n=113) based on clinical ultrasonographic examination reports near enrollment. Archived plasma samples were newly sequenced and normalized chromosome values were determined. Aneuploidy classifications for chromosomes 21, 18, 13, and X were made using the massively parallel sequencing data by laboratory personnel blinded to fetal karyotype and compared for analysis.

Results: : Sixty-nine of 113 (61%) patients had fetuses with abnormal karyotypes, including trisomy 21 (n=30), monosomy X (n=21), trisomy 18 (n=10), trisomy 13 (n=4), and other (n=4). There were 44 euploid cases; none was called positive for aneuploidy. The massively parallel sequencing detection rates were as follows: T21: 30 of 30, T18: 10 of 10, T13: three of four, and monosomy X: 20 of 21, including two complex mosaic cases. Overall, using massively parallel sequencing results of the four studied chromosomes, 107 of 113 (95%, 95% confidence interval [CI] 88.8-98.0) cases were accurately called by massively parallel sequencing, including 63 of 65 (97%, 95% CI 89.3-99.6) of cases of whole chromosome aneuploidy.

Conclusion: : Massively parallel sequencing provides an accurate way of detecting the most prevalent aneuploidies associated with cystic hygroma. Massively parallel sequencing could advance prenatal care by providing alternative point-of-care noninvasive testing for pregnant women who either decline or do not have access to an invasive procedure.

Clinical trial registration:,, NCT01122524.

Level of evidence: II.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • DNA, Neoplasm / blood*
  • Female
  • Fetal Diseases / genetics*
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Lymphangioma, Cystic / genetics*
  • Pregnancy
  • Sequence Analysis, DNA / methods
  • Young Adult


  • DNA, Neoplasm

Associated data