Copy number variation (CNV) analysis is a powerful tool for discovering structural genomic variation. Still, no program uses this tool to analyze chromosomal aneuploidies in the Vietnamese population. Pregnant women attending routine prenatal checkups in Vietnam from October 2018 to May 2021 were included in this study and contributed fetal tissue to test the utility of CNV analysis for prenatal screening. Among 5,008 women screened, 958 (19.13%) harbored at least one CNV, comprising segmental aneuploidy (8.49%), trisomy (6.91%), multiple anomalies (2.10%), and sex chromosome abnormality (1.64%). The rate of segmental aneuploidy detection increased with gestational age, but trisomy and sex chromosomal abnormalities detection decreased as the pregnancy continued. This study also found an association between abnormal CNVs and several phenotypic markers. For ultrasound soft markers, an increased nuchal fold thickness correlated with a higher risk of abnormal CNVs. In addition, many soft indicators or structural abnormalities were significantly associated with an increased likelihood of abnormal CNVs. This work highlights the importance of CNV analysis for the early detection of prenatal congenital abnormalities, especially in the first trimester. This study’s findings will meaningfully aid policymakers in developing cost-effective genetic prenatal screening programs.
Abstractα-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/−−SEA (4.066%), αα/−α3.7 (2.934%), αα/−α4.2 (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14–99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (−α3.7/−α4.2, αα/−−THAI, −α3.7/−−SEA, −α4.2/−−SEA). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/−−SEA, 94.87% for αα/−α3.7, and 96.51% for αα/−α4.2; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.
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