Abstract
BackgroundNon-invasive prenatal screening (NIPS) is a highly sensitive and specific screening test to detect fetal chromosomal abnormalities. The primary objective of this study was to evaluate the NIPS as an effective method for prenatal detection of aneuploidies in both high-risk and low-risk pregnancies.MethodsIn current study, we performed NIPS in 32,394 pregnancies, out of which results were available in 32,361 (99.9%) of them. Illumina sequencing was performed for NIPS screening. Hypothesis Z test was used to classify fetal autosomal aneuploidy of T21, T18, and T13. Karyotyping was performed to determine the true negative and true positive NIPS results.ResultsAmong the 32,361 confirmed samples, 164 cases had positive results and 32197 cases had negative results. Of these positive cases, 116 cases were trisomy 21, 34 cases were trisomy 18 and 14 cases were trisomy 13. No false negative results were found in this cohort. The overall sensitivity and specificity were 100% and 99.91%, respectively. There was no significant difference in test performance between the 7,316 high-risk and 25,045 low-risk pregnancies, (sensitivity, 100% vs 100% (P>0.05); specificity, 99.96% vs 99.95% (P > 0.05)). Factors contributing to false-positive results included fetal copy number variants (CNVs), fetal mosaicism and typically producing Z scores between 3 and 4. Moreover, we analyzed NIPS wholegenome sequencing to investigate the Single Nucleotide Polymorphisms (SNPs) associations with drug response or risk of disease. As compare to the 1000g East Asian genome data, the results revealed a significant difference in 7,285,418 SNPs variants of Shanxi pregnant women including 19,293 clinvar recorded variants and 7,266,125 non-clinvar recorded.ConclusionsOur findings showed that NIPS was an effective assay that may be applied as routine screening for fetal trisomies in the prenatal setting. In addition, this study also provides an accurate assessment of significant differences in 7,285,418 SNPs variants in Shanxi pregnant women that were previously unavailable to clinicians in Shanxi population.
Highlights
China has the largest number of birth defects in the world, with about 900,000 new cases of birth defects every year [1], including about 240,000 cases of chromosomal abnormalities, most of which cannot be cured till today [2]
As compare to the 1000g East Asian genome data, the results revealed a significant difference in 7,285,418 Single Nucleotide Polymorphisms (SNPs) variants of Shanxi pregnant women including 19,293 clinvar recorded variants and 7,266,125 non-clinvar recorded
There was no significant difference in test performance between the 7,316 highrisk and 25,045 low-risk subjects (sensitivity, 100% vs. 100% (P >0.05); specificity, 99.96% vs. 99.95% (P > 0.05)). These results suggested that the application of non-invasive prenatal screening (NIPS) could significantly reduce the cost of invasive prenatal diagnosis, which had a positive yield of only 0.56% (41/7,316) in high-risk group and 0.29% (73/25,045) in low-risk group
Summary
China has the largest number of birth defects in the world, with about 900,000 new cases of birth defects every year [1], including about 240,000 cases of chromosomal abnormalities, most of which cannot be cured till today [2]. The concentration of cfDNA in the maternal plasma circulation may vary widely [5, 6], ranging from 4% to over 30% [7] Advanced technologies such as digital polymerase chain reaction or massively parallel sequencing have been used to study cfDNA in maternal blood, differentiate fetal DNA from maternal DNA, and detect fetal chromosomal abnormalities [8]. These discoveries made non-invasive prenatal screening (NIPS) of fetal aneuploidies a clinical reality and led to a new era of non-invasive prenatal screening with high sensitivity and specificity in multiple clinical centers [9, 10]. We investigated the SNPs induced risk of disease based on 32,394 samples obtained from the Changzhi Maternal and Child Health Care Hospital, and SNPs induced variation in drug response
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