The impact of prenatal screening tests on prenatal diagnosis in Taiwan from 2006 to 2019: a regional cohort study.

BACKGROUND: The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan's 14 years from 2006 to 2019. METHODS: The prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website. RESULTS: This regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively. CONCLUSION: During the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased.

Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women.

Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.

Current status of non-invasive prenatal testing in Japan.

AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Overview of the impact of noninvasive prenatal testing on diagnostic procedures.

Noninvasive prenatal testing (NIPT) has had a profound influence in the field of prenatal diagnosis since the 1997 discovery of cell-free fetal DNA in maternal blood. Research has progressed rapidly, with clinical data supporting laboratory studies showing that NIPT is highly sensitive and specific for fetal aneuploidy, resulting in marked uptake in the high-risk patient population. The superior accuracy of NIPT compared with conventional screening methods has led to significant decreases in the number of invasive diagnostic procedures, in addition to a concomitant decrease in the number of procedure-related fetal losses. Yet, NIPT has been described as a 'disruptive innovation' due to the considerable changes the technology has commanded on current prenatal screening and diagnostic practices. This review summarizes both institutional and global experience with NIPT uptake, its effect on reducing diagnostic invasive procedures, and the unique challenges that reduced procedural volume may have on physician and trainee proficiency, cytogenetic laboratories, and neonatal outcome.

An Overview on Prenatal Screening for Chromosomal Aberrations.

This article is a review of current and emerging methods used for prenatal detection of chromosomal aneuploidies. Chromosomal anomalies in the developing fetus can occur in any pregnancy and lead to death prior to or shortly after birth or to costly lifelong disabilities. Early detection of fetal chromosomal aneuploidies, an atypical number of certain chromosomes, can help parents evaluate their pregnancy options. Current diagnostic methods include maternal serum sampling or nuchal translucency testing, which are minimally invasive diagnostics, but lack sensitivity and specificity. The gold standard, karyotyping, requires amniocentesis or chorionic villus sampling, which are highly invasive and can cause abortions. In addition, many of these methods have long turnaround times, which can cause anxiety in mothers. Next-generation sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive, and reasonably rapid analysis of fetal chromosomal anomalies and can be of clinical utility to parents. This review covers traditional methods and next-generation sequencing techniques for diagnosing aneuploidies in terms of clinical utility, technological characteristics, and market potential.