Validation of fetal DNA fraction estimation and its application in noninvasive prenatal testing for aneuploidy detection in multiple pregnancies

Abstract

Objective To analyze the fetal fraction, fetal sex, and chromosomal aneuploidy in multiple pregnancies using noninvasive prenatal testing (NIPT). Method A total of 362 pregnant women including 203 singleton pregnancies, 69 twins, and 90 higher‐order multiple pregnancies were recruited. Fetal fractions estimated by size ratio‐based and Y chromosome‐based approaches in singleton pregnancies with male fetus were used as source data to establish the model. The model was then applied to multiple pregnancies for fetal fraction estimation. By comparing the fetal fractions estimated by size ratio to those estimated by Y chromosome or autosomal chromosomes, fetal sex and chromosomal aneuploidy can be analyzed. Results The size ratio‐based approach has been well established in estimating fetal fractions for twin and higher‐order multiple pregnancies. Fetal fraction had a positive correlation with gestational age in twin and triplet pregnancies. Fetal sex was determined with accuracies of 98.6% (95% CI, 92.19%‐99.96%) in twins and 97.6% (95% CI, 91.76%‐99.71%) in triplet pregnancies. Four trisomy 21, one trisomy 18, and one trisomy 13 cases were detected by NIPT. Two trisomy 21 singleton pregnancies and one trisomy 21 twin pregnancy were confirmed by karyotyping. Conclusion Fetal sex and chromosomal aneuploidy in multiple pregnancies can be determined using NIPT.

Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations

“…Few labs have performed NIPT in triplets and higher-order multiples, as large data sets are difficult to collect. Correct interpretation of NIPT and accurate determination of fetal sex seem achievable in triplet pregnancies, 2,21 as demonstrated in our cohort of 25 triplets, but more studies with larger cohorts and positive cases are required. In our opinion, NIPT would be a valuable screening option for higherorder multiples, because maternal serum markers cannot be applied and current screening is based on ultrasonography and maternal age only.…”

“…Studies on the accuracy of NIPT in twin pregnancies are limited and include relatively small numbers. 2,[15][16][17][18][19][20][21][22][23] This study reports on one of the largest cohorts of women with a twin gestation undergoing screening for aneuploidy with NIPT, and demonstrates high sensitivity and specificity for detection of trisomy 21 in dichorionic-diamniotic twins.…”

International Society for Prenatal Diagnosis Position Statement: cell free (cf)DNA screening for Down syndrome in multiple pregnancies

“…56 That review included only population-based studies and did not include eight additional studies that were either of case/control design or were published after that review was completed. 53,55,[58][59][60][61][62][63] Table 2 predictive values are expected to be similar to those found in screen positive singleton pregnancies.…”

Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction

“…Additionally, based on the previously reported combined FF value in twin pregnancies (ranging from approx. 7% to 35%) [31], we did not suppose dropout probability d = 0 for individual fetus because it is fallacious for the minor contributors of cfDNA mixtures. Instead, we set the min.…”