Cell-free DNA screening for common autosomal trisomies using rolling-circle replication in twin pregnancies

Area of Science:

• Genetics
• Maternal-Fetal Medicine
• Molecular Diagnostics

Background:

• Prenatal screening for autosomal trisomies is crucial for identifying chromosomal abnormalities.
• Twin pregnancies present unique challenges for accurate prenatal screening.
• Cell-free DNA (cfDNA) testing has emerged as a promising non-invasive prenatal screening method.

Purpose of the Study:

• To evaluate the performance of rolling-circle replication (RCR)-cfDNA as a first-tier prenatal screening test for common autosomal trisomies in twin pregnancies.
• To compare the no-call rate of RCR-cfDNA in twin pregnancies with that in singleton pregnancies.
• To assess the sensitivity and specificity of RCR-cfDNA for detecting trisomy 21, 18, and 13 in twins.

Main Methods:

• A prospective multicenter study included 862 twin pregnancies undergoing RCR-cfDNA screening for trisomies 21, 18, and 13.
• The primary endpoint was the rate of no-call results compared to a historical cohort of singleton pregnancies.
• Secondary endpoints included performance indices such as sensitivity and specificity.

Main Results:

• The RCR-cfDNA test yielded a no-call result in 2.0% of twin pregnancies, compared to 0.7% in singletons.
• Twin pregnancy and in vitro fertilization conception were identified as predictors of test failure.
• The test demonstrated 100% sensitivity for trisomies 21, 18, and 13 in twin pregnancies, with high detection rates for each trisomy.

Conclusions:

• RCR-cfDNA testing is an accurate first-tier screening method for common autosomal trisomies in twin pregnancies.
• The test exhibits a low no-call rate and high sensitivity, making it suitable for twin gestation.
• This approach enhances prenatal diagnostic capabilities for common aneuploidies in multiple gestations.