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NIPT Trisomy 21 Screening Works Equally Well in Twin and Singleton Pregnancies, Study Finds

NEW YORK (GenomeWeb) – Cell-free DNA screening of maternal blood for fetal trisomy 21 is as effective in twin pregnancies as in singleton pregnancies, according to a new study.

Researchers led by Kypros Nicolaides at King's College Hospital in London collected data from fetal cfDNA testing for trisomies 21, 18, and 13 in twin pregnancies that was performed during the first trimester. Most previous analyses of noninvasive prenatal testing performance have focused on singleton pregnancies, where it has been shown to be an effective means of identifying trisomies 21, 18, and 13.

Also, guidelines issued by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine in 2016 do not recommend cfDNA screening in cases of multiple gestations.

As they reported this week in Ultrasound in Obstetrics & Gynecology, the researchers found cfDNA testing could correctly classify trisomy 21 cases more than 94 percent of the time in their dataset. When they included previously published data in their analysis, they could detect 98 percent of trisomy 21 cases. This, they noted, is similar to what has been reported in singleton pregnancies.

"The results of our study and the meta-analysis of cfDNA testing of maternal blood in twin pregnancies suggest that the performance of the test for trisomy 21 may be similar to that in singleton pregnancies," Nicolaides and his colleagues wrote in their paper.

For their study, which aimed to update results from the Fetal Medicine Foundation, Nicolaides and his colleagues collected data on 997 twin pregnancies that underwent cfDNA testing and for which there was a known karyotype. This study population included mostly fraternal twin pregnancies but also identical twin pregnancies. In all, the cohort included 17 cases with trisomy 21, 10 with trisomy 18, two with trisomy 13, and one identical twin case in which both twins had trisomy 18.

In this cohort, cfDNA testing — using Roche's Ariosa Diagnostics Harmony test — correctly classified 94 percent of the 17 trisomy 21 cases, 90 percent of the trisomy 18 cases, and one of the two trisomy 13 cases. Testing classified one case from each of the trisomies as negative when it was positive, and four cases were classified as a trisomy when they were not. The combined false positive rate was 0.62 percent.

The researchers also conducted a literature search through which they identified seven articles that also examined cfDNA analysis of maternal blood for trisomies in twin pregnancies, mostly using sequencing-based approaches. They then combined these with their own results into a meta-analysis.

For the pooled 56 trisomy 21 cases and 3,718 non-trisomy 21 twin pregnancies, cfDNA testing had a weighted detection rate of 98.2 percent and a false positive rate of 0.05 percent. Meanwhile, for trisomy 18 in twin pregnancies, cfDNA testing had a pooled weighted detection rate of 88.9 percent and false positive rate of 0.03 percent.

By comparison, the researchers' previously published analysis of singleton pregnancies found cfDNA testing had a detection rate of 99.7 percent and false positive rate of 0.04 percent for trisomy 21 and a detection rate of 97.9 percent and false positive rate of 0.04 percent for trisomy 18 pregnancies.

This suggests cfDNA testing for trisomy 21 in twin pregnancies may be as good as testing in singleton pregnancies, the researchers said.

"Performance of cfDNA testing for trisomy 21 in twin pregnancies is similar to that reported in singleton pregnancies and is superior to that of the first-trimester combined test or second-trimester biochemical testing," they concluded.

The number of twin pregnancies with trisomy 18 and trisomy 13 was too small to assess the predictive performance of cfDNA testing accurately, they wrote, noting that the false positive rate for trisomy 13 appeared to be slightly higher than for singleton pregnancies.