Noninvasive Prenatal Testing For Aneuploidy Detection By Size Ratio-Based In Pregnancies

The use of cff DNA in clinical applications offers opportunities for reading genetic information of fetuses by NIPT.Twin and higher-order multiple pregnancies become more prevalent,with the development of assisted reproductive technology(ART).However,application of NIPT for multiple pregnancies is limited.The sensitivity is reduced by 9% for trisomy 21(T21),28% for trisomy 18(T18),and 22% for trisomy13(T13)in twin pregnancies compared to those in singleton pregnancies.Accuracy of NIPT is affected by the fetal fraction,which requires at least 4% for sensitive screening.Low fetal fraction may give rise to false negative Results or higher test failure rates.Therefore,it is important to estimate the fetal fraction accurately so that NIPT Results can be reliably interpreted.Recently,taking advantage of the fact that maternal plasma and fetal DNA exhibit different fragmentation patterns,a cell-free DNA size ratio-based approach has been developed to directly deter mine fetal fraction from the plasma sequencing data.Here,we conducted a study to evaluate this approach in measuring fetal fraction in multiple pregnancies and further extended this approach to detect fetal sex and chromosomal aneuploidy in multiple pregnancies.A total of 362 pregnant women including 203 singleton pregnancies,69 twins and 90higher-order multiple pregnancies were recruited.Fetal fractions estimated by size ratio-based and Y chromosome-based approach in singleton pregnancies with male fetus were used as training data to establish the model.The model was applied to multiple pregnancies for fetal fraction estimation.By comparing the fetal fractions estimated by size-ratio to those by Y chromosome or autosomal chromosomes,fetal sex and chromosomal aneuploidy were further analyzed.