Noninvasive prenatal screening in twin pregnancies


The investigators found an extremely low failure rate of 0.31%.

Cell-free DNA (cfDNA) testing of maternal blood is the most accurate screening test for the common fetal trisomy 21 in twin pregnancies and mirrors the screening performance for singletons, according to a large multicenter prospective study in the American Journal of Obstetrics & Gynecology.

The investigators found an extremely low failure rate of 0.31%.

Because of a low false positive rate, “offering first line screening with cfDNA to women with twin pregnancy is appropriate in our view, and should be considered as a primary screening test for trisomy 21 in twins,” wrote the authors who are based in the United Kingdom.

The potential advantages of noninvasive prenatal testing (NIPT) in twin pregnancies are even greater than in singletons, according to the authors, noting less need for invasive testing and subsequent possible fetal loss.

Nonetheless, many organizations do not recommend cfDNA in twin pregnancies and advocate larger prospective studies.

Thus the motivation for the current study, which combined its own data with published studies to glean the best estimate of screening performance.

The blinded study evaluating the screening performance of cfDNA in maternal plasma for detecting fetal trisomies in twin pregnancies was conducted at six fetal medicine centers in England between February 2015 and June 2018.

The primary outcome was the screening performance and test failure rate of cell-free DNA using the IONA test for next-generation sequencing.

Maternal blood was taken at either the time of or after a conventional screening test.

The study also included a pooled analysis of the study’s data with 11 studies from a literature search of MEDLINE, EMBASE, CENTRAL, The Cochrane Library and

Eligible women for the current study were at least aged 16 with fetal ultrasound verifying a viable twin pregnancy of at least 10 weeks of gestation. Of the 961 women with complete data, follow-up and reference data, 276 were monochorionic and 685 were dichorionic.

Besides a mere 0.31% failure rate for trisomy 21 with the IONA test, the mean fetal fraction was 12.2%, ranging from 3% to 36%; however, all 9 samples with a 3% fetal fraction achieved a valid result.

There were no false positive or false negative results for trisomy 21 or trisomy 13, but there was one false negative and one false positive result for trisomy 18.

The IONA test had a detection rate of 100% for trisomy 21 (n = 13), 0% for trisomy 18 (n = 1) and 100% for trisomy 13 (n = 1).

The corresponding false positive rates were 0%, 0.10% and 0%, respectively.

By combining data from the study with the 11 studies from the literature search, the detection rate for trisomy 21 was 95% (n = 74) and the false positive rate was 0.09% (n = 5,598).

The corresponding values for trisomy 18 were 82% (n = 22) and 0.08% (n = 4,869), respectively.

There were also five cases of trisomy 13 and 3,881 non-trisomy-13 pregnancies, resulting in a computed average detection rate of 80% and a false positive rate of 0.13%.

“The greater likelihood of trisomy 21 in multiple pregnancy, higher FPR of other screening approaches, higher likelihood of being offered invasive testing, and the greater likelihood of complications of invasive testing all mean that cfDNA has an important role to play in screening for trisomies in twins,” the authors concluded.


Khalil A, Archer R, Hutchinson V, et al. Non-invasive prenatal screening in twin pregnancies with cell-free DNA using the IONA test: a prospective multicentre study. Am J Obstet Gynecol. Published online January 15, 2021. doi:10.1016/j.ajog.2021.01.005

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