Performance of screening for aneuploidies by cell-free DNA analysis of maternal blood in twin pregnancies

Ultrasound Obstet Gynecol. 2015 Jan;45(1):61-6. doi: 10.1002/uog.14690. Epub 2014 Dec 4.


Objectives: To report clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood in screening for trisomies 21, 18 and 13 in twin pregnancies and examine variables that could influence the failure rate of the test.

Methods: cfDNA testing was performed in 515 twin pregnancies at 10-28 weeks' gestation. The failure rate of the test to provide results was compared with that in 1847 singleton pregnancies, and logistic regression analysis was used to determine which factors among maternal and pregnancy characteristics were significant predictors of test failure.

Results: Failure rate of the cfDNA test at first sampling was 1.7% in singletons and 5.6% in twins. Of those with a test result, the median fetal fraction in twins was 8.7% (range, 4.1-30.0%), which was lower than that in singletons (11.7% (range, 4.0-38.9%)). Multivariable regression analysis demonstrated that twin pregnancy, higher maternal weight and conception by in-vitro fertilization provided significant independent prediction of test failure. Follow-up was available in 351 (68.2%) of the twin pregnancies and comprised 334 with euploid fetuses, 12 discordant for trisomy 21 and five discordant for trisomy 18. In all 323 euploid cases with a result, the risk score for each trisomy was < 1:10 000. In 11 of the 12 cases with trisomy 21 and in the five with trisomy 18, the cfDNA test gave a high-risk result, but in one case of trisomy 21, the score was < 1:10 000.

Conclusion: In twin pregnancies screening by cfDNA testing is feasible, but the failure rate is higher and detection rate may be lower than in singletons.

Keywords: aneuploidies; cell-free DNA; screening test; trisomies; twin pregnancies.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell-Free System
  • Chorionic Gonadotropin, beta Subunit, Human / blood*
  • DNA / blood*
  • False Positive Reactions
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Male
  • Maternal Age
  • Pregnancy
  • Pregnancy, Twin / blood*
  • Pregnancy-Associated Plasma Protein-A / metabolism*
  • Prenatal Diagnosis*
  • Prospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Trisomy / diagnosis*


  • Chorionic Gonadotropin, beta Subunit, Human
  • DNA
  • Pregnancy-Associated Plasma Protein-A