Outcomes in Pregnancies With a Confined Placental Mosaicism and Implications for Prenatal Screening Using Cell-Free DNA

Grati, Francesca Romana; Ferreira, José Carlos; Benn, Peter; Izzi, Claudia; Verdi, Federica; Vercellotti, E; Dalpiaz, Cristina; D’Ajello, Patrizia; Filippi, Elisa; Volpe, N.; Malvestiti, Francesca; Maggi, Federico; Simoni, Giuseppe; Frusca, T.; Cirelli, Gaetana; Bracalente, Gabriella; Re, Antonino Lo; Surico, Daniela; Ghi, T.; Prefumo, Federico

doi:10.1097/01.ogx.0000688044.66625.e4

Cited by 15 publications

(21 citation statements)

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“…The presence of confined placental mosaicism could explain a positive NIPS result for rare aneuploidy and results in a high discordance rate between NIPS and invasive diagnosis by amniocentesis. Notably, confined placental mosaicism for RAT is not associated with an increased risk of fetal anomalies and pregnancy complications, as compared to cases with a normal karyotype on invasive diagnosis by CVS 25 . Therefore, when rare aneuploidy is reported by NIPS, the specimen source for invasive diagnostic testing should be considered carefully and caution should be taken when interpreting results from CVS or placental studies 3 .…”

Section: Discussionmentioning

confidence: 99%

Clinical utility of expanded non‐invasive prenatal screening and chromosomal microarray analysis in high‐risk pregnancy

Zhu

Chen

Wang

et al. 2021

Ultrasound in Obstet & Gyne

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Objective To evaluate the utility of expanded non‐invasive prenatal screening (NIPS), compared with chromosomal microarray analysis (CMA), for the detection of chromosomal abnormalities in high‐risk pregnancies. Methods This was a multicenter retrospective study of singleton pregnancies at high risk for chromosomal abnormality. Patients who underwent expanded NIPS and CMA sequentially during pregnancy from 2015 to 2019 were included in the analysis. Pregnancies with a positive result for sex chromosome aneuploidy were excluded as the full details could not be retrieved. The utility of expanded NIPS and CMA for detection of chromosomal abnormalities in this cohort was compared by assessing the concordance between the results. Results Of the 774 included high‐risk pregnancies, 550 (71.1%) had a positive NIPS result, while a positive CMA result was detected in 308 (39.8%) cases. The rate of full or partial concordance between NIPS and CMA was 82.2%, 59.6% and 25.0% for trisomies 21, 18 and 13, respectively. For rare aneuploidies and segmental imbalances, NIPS and CMA results were fully or partially concordant in 7.5% and 33.3% of cases, respectively. Copy‐number variants < 5 Mb were detected more often by CMA, with an incidence of 7.9% (61/774) compared with 3.1% (24/774) by NIPS. A genetic aberration was detected by CMA in 1 in 17 (5.8%) high‐risk pregnancies that had a negative or non‐reportable NIPS result. Conclusion CMA allows for comprehensive detection of genome‐wide chromosomal abnormalities in high‐risk pregnancies. CMA should be offered instead of expanded NIPS for high‐risk pregnancies. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

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Section: Discussionmentioning

confidence: 99%

Clinical utility of expanded non‐invasive prenatal screening and chromosomal microarray analysis in high‐risk pregnancy

Zhu

Chen

Wang

et al. 2021

Ultrasound in Obstet & Gyne

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“…A previous study suggested that mosaicisms from CVS should be further verified for TFM by AF or CB due to the presence of fetoplacental discrepancies 19 . However, although most pregnancies diagnosed with CPM are deemed to have good postnatal outcomes but an impaired placenta may provide insufficient support for the pregnancy, leading to foetal complications such as FGR or other adverse outcomes 20,21 . Therefore, continuous monitoring of foetal growth during pregnancy is important to prevent adverse complications for foetuses with TFM and CPM.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis

Zhang

Zhong

Zheng

2020

J Cellular Molecular Medi

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Chromosomal mosaicism (CM) is a biological phenomenon defined as an individual who has arisen from a single zygote and has two or more populations of cells with distinct genotypes. 1 The main underlying mechanisms leading to mosaicism formation involve mitotic or meiotic non-disjunction errors, anaphase lagging and trisomy rescue, endoreplication events, and uniparental disomy (UPD) associated with trisomy rescue. 2 Theoretically, the pattern of the mosaic distribution in the foetus and placenta is largely determined by the

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“…A major known cause of placental insufficiency in a viable pregnancy is confined placental mosaicism (CPM), where some or most cells in the placenta are aneuploid, while the fetus has a predominantly normal diploid chromosome complement. CPM identified prenatally is associated with increased risk for FGR and other pregnancy complications depending on the levels of abnormal cells and the chromosome(s) involved (Robinson et al 1997;Grati et al 2019). Screening placentas postnatally has also confirmed a contribution of CPM to FGR (Artan et al 1995;Krishnamoorthy et al 1995;Wilkins-Haug et al 1995;Stipoljev et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Genomic imbalances in the placenta are associated with poor fetal growth

Gobbo

Yin

Choufani

et al. 2021

Mol Med

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Background Fetal growth restriction (FGR) is associated with increased risks for complications before, during, and after birth, in addition to risk of disease through to adulthood. Although placental insufficiency, failure to supply the fetus with adequate nutrients, underlies most cases of FGR, its causes are diverse and not fully understood. One of the few diagnosable causes of placental insufficiency in ongoing pregnancies is the presence of large chromosomal imbalances such as trisomy confined to the placenta; however, the impact of smaller copy number variants (CNVs) has not yet been adequately addressed. In this study, we confirm the importance of placental aneuploidy, and assess the potential contribution of CNVs to fetal growth. Methods We used molecular-cytogenetic approaches to identify aneuploidy in placentas from 101 infants born small-for-gestational age (SGA), typically used as a surrogate for FGR, and from 173 non-SGA controls from uncomplicated pregnancies. We confirmed aneuploidies and assessed mosaicism by microsatellite genotyping. We then profiled CNVs using high-resolution microarrays in a subset of 53 SGA and 61 control euploid placentas, and compared the load, impact, gene enrichment and clinical relevance of CNVs between groups. Candidate CNVs were confirmed using quantitative PCR. Results Aneuploidy was over tenfold more frequent in SGA-associated placentas compared to controls (11.9% vs. 1.1%; p = 0.0002, OR = 11.4, 95% CI 2.5–107.4), was confined to the placenta, and typically involved autosomes, whereas only sex chromosome abnormalities were observed in controls. We found no significant difference in CNV load or number of placental-expressed or imprinted genes in CNVs between SGA and controls, however, a rare and likely clinically-relevant germline CNV was identified in 5.7% of SGA cases. These CNVs involved candidate genes INHBB, HSD11B2, CTCF, and CSMD3. Conclusions We conclude that placental genomic imbalances at the cytogenetic and submicroscopic level may underlie up to ~ 18% of SGA cases in our population. This work contributes to the understanding of the underlying causes of placental insufficiency and FGR, which is important for counselling and prediction of long term outcomes for affected cases.

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Outcomes in Pregnancies With a Confined Placental Mosaicism and Implications for Prenatal Screening Using Cell-Free DNA

Cited by 15 publications

References 0 publications

Clinical utility of expanded non‐invasive prenatal screening and chromosomal microarray analysis in high‐risk pregnancy

Clinical utility of expanded non‐invasive prenatal screening and chromosomal microarray analysis in high‐risk pregnancy

Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis

Genomic imbalances in the placenta are associated with poor fetal growth

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