Contingent prenatal screening for frequent aneuploidies with cell-free fetal DNA analysis

Aguilar, Marta; Salas, Pilar Carrasco; Rosa, Cristina Santos; Rodríguez, Guadalupe Bueno; Martínez-Bonet, Eduardo; Alba, Práxedes Carreto; León-Justel, Antonio; Escobar, Milagro

doi:10.1016/j.tjog.2021.05.028

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…QF-PCR was performed using the Devyser Compact v3 kit, and the markers specific to the chromosomes 13, 18, 21, X, and Y were amplified ( Torres et al, 2021 ). The amplified markers were then subjected to capillary electrophoresis.…”

Section: Methodsmentioning

confidence: 99%

Identification of genetic alterations in couples and their products of conceptions from recurrent pregnancy loss in North Indian population

et al. 2023

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Background: Recurrent pregnancy loss (RPL) is one of the most common pregnancy-related complications, which can be stressful and emotionally draining for a couple. Genetic alterations, which are responsible for RPL, can be present in either of the three genomes: mother, father, or their fetuses. In addition, environmental factors interacting with these three genomes can affect germline cells. With this aim, the present study was conducted to understand the underlying etiology of RPL using Next-generation sequencing (NGS; couple exome and TRIO exomes) in combination with cytogenetic tests [karyotyping and chromosomal microarray (CMA)].Material & Methods: In present study we recruited 61 couples with RPL (history of ≥ 2 abortions) and 31 products of conceptions (POCs). For all couples karyotyping was done at the time of recruitment, followed by collection of POC samples and parental blood samples. Before processing POC samples for CMA, they were checked for maternal cell contamination (MCC) by QF-PCR. In POC samples with no pathogenic variant, TRIO exome sequencing was done. Further, in case of unavailability of POC sample, couple exome sequencing was done for RPL couples.Results: In six individuals out of 61 couples (5%), abnormality in karyotypes was detected. Among 116 normal karyotypes, there were 11 heteromorphisms (9.5%), for which the couples had to be counselled and reassured. Out of the 31 POCs, 10 were excluded because of MCC (around 30%) and one had major aneuploidy. CMA in POCs identified pathogenic copy number variations (CNVs) in 25% of cases (5/20) and variant of unknown significance (VUS) in 20% of cases (4/20). Autosomal trisomy was the most frequent chromosomal abnormality diagnosed. NGS was performed to establish single-gene causes of RPL. Couple exome sequencing was performed in 20 couples, and 14 were found to be carriers for autosomal recessive conditions. A total of 50 potential disease-causing variants in 40 genes were identified in 33 of 40 individuals (82.5%). Putative causative variants were identified in 37.5% of the TRIO cases (3/8). Mutations in few important genes (SRP54, ERBB4, NEB, ALMS, ALAD, MTHFR, F5, and APOE), which are involved in vital pathways, early embryonic development, and fetal demise, were identified in the POCs.Conclusion: It enhances our understanding of prenatal phenotypes of many Mendelian disorders. These mutated genes may play an auxiliary role in the development of treatment strategies for RPL. There was no correlation of the number of abortions with etiological yield of any technique to detect the cause of RPL. This study shows the utilization of combination of techniques in improving our understanding of the cause of early embryonic lethality in humans.

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Section: Methodsmentioning

confidence: 99%

Identification of genetic alterations in couples and their products of conceptions from recurrent pregnancy loss in North Indian population

et al. 2023

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“…Twenty-one manuscripts met the inclusion criteria for part A, reporting on 27 countries, states or autonomous regions in Europe, North America and Asia that implemented NIPT as part of a recommended antenatal screening policy for DS between 2011 and 2023 (Fig 2). Eight were retrospective cohort studies of population-based data [11,13,15,20,21,[26][27][28], evaluating the implementation of NIPT into their screening programmes for DS, and four were prospective cohort studies [14,[29][30][31]. Also included were eight official government documents describing the implementation of NIPT [12,[32][33][34][35][36][37][38] and one study that undertook a survey of clinical experts worldwide, providing data on multiple countries [16].…”

Section: Part A-the Implementation and Uptake Of Nipt In National Ant...mentioning

confidence: 99%

The implementation and impact of non-invasive prenatal testing (NIPT) for Down’s syndrome into antenatal screening programmes: A systematic review and meta-analysis

Sebire,

Rodrigo,

Bhattacharya

et al. 2024

PLoS ONE

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Background Non-invasive prenatal testing (NIPT) is a widely adopted maternal blood test that analyses foetal originating DNA to screen for foetal chromosomal conditions, including Down’s syndrome (DS). The introduction of this test, which may have implications for important decisions made during pregnancy, requires continual monitoring and evaluation. This systematic review aims to assess the extent of NIPT introduction into national screening programmes for DS worldwide, its uptake, and impact on pregnancy outcomes. Methods and findings The study protocol was published in PROSPERO (CRD42022306167). We systematically searched MEDLINE, CINAHL, Scopus, and Embase for population-based studies, government guidelines, and Public Health documents from 2010 onwards. Results summarised the national policies for NIPT implementation into screening programmes geographically, along with population uptake. Meta-analyses estimated the pooled proportions of women choosing invasive prenatal diagnosis (IPD) following a high chance biochemical screening result, before and after NIPT was introduced. Additionally, we meta-analysed outcomes (termination of pregnancy and live births) amongst high chance pregnancies identified by NIPT. Results demonstrated NIPT implementation in at least 27 countries. Uptake of second line NIPT varied, from 20.4% to 93.2% (n = 6). Following NIPT implementation, the proportion of women choosing IPD after high chance biochemical screening decreased from 75% (95% CI 53%, 88%, n = 5) to 43% (95%CI 31%, 56%, n = 5), an absolute risk reduction of 38%. A pooled estimate of 69% (95% CI 52%, 82%, n = 7) of high chance pregnancies after NIPT resulted in termination, whilst 8% (95% CI 3%, 21%, n = 7) had live births of babies with DS. Conclusions NIPT has rapidly gained global acceptance, but population uptake is influenced by healthcare structures, historical screening practices, and cultural factors. Our findings indicate a reduction in IPD tests following NIPT implementation, but limited pre-NIPT data hinder comprehensive impact assessment. Transparent, comparable data reporting is vital for monitoring NIPT’s potential consequences.

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Discordant performances of non-invasive prenatal testing for foetal trisomy 21 screening in subgroups of pregnancies

Suo,

Wang,

Wang

et al. 2023

Journal of Obstetrics and Gynaecology

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Contingent prenatal screening for frequent aneuploidies with cell-free fetal DNA analysis

Cited by 4 publications

References 21 publications

Identification of genetic alterations in couples and their products of conceptions from recurrent pregnancy loss in North Indian population

Identification of genetic alterations in couples and their products of conceptions from recurrent pregnancy loss in North Indian population

The implementation and impact of non-invasive prenatal testing (NIPT) for Down’s syndrome into antenatal screening programmes: A systematic review and meta-analysis

Discordant performances of non-invasive prenatal testing for foetal trisomy 21 screening in subgroups of pregnancies

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