The accuracy of prenatal cell-free DNA screening for sex chromosome abnormalities: A systematic review and meta-analysis

Bussolaro, Sofia; Raymond, Y.C.; Acreman, Melissa L.; Guido, Maurizio; Costa, Fabrício da Silva; Rolnik, Daniel L.; Fantasia, Ilaria

doi:10.1016/j.ajogmf.2022.100844

Cited by 8 publications

(8 citation statements)

References 108 publications

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Section: Discussionsupporting

confidence: 91%

“…PPVs for CAT, SCA and RAT in our study were similar to those reported in previous studies 10,11,16,17 . PPVs in cases at high risk for T13 and T18, both with and without ultrasound findings, were similar to those reported by Zhen et al 18 , although the larger cohort size in the present study allowed a statistically significant difference to be observed between cases with normal and abnormal ultrasound.…”

Section: Discussionsupporting

confidence: 91%

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Late first‐trimester ultrasound findings can alter management after high‐risk NIPT result

Scott,

Smet,

Elhindi

et al. 2023

Ultrasound in Obstet & Gyne

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ObjectiveTo evaluate the impact of a detailed late first‐trimester ultrasound (LTFU) on the positive predictive value (PPV) of a high‐risk non‐invasive test (NIPT) result for various aneuploidies.MethodsThis was a retrospective study of all cases undergoing invasive prenatal testing from 3 tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first line screening test. Data was collected from the pre‐NIPT ultrasound, NIPT results, LFTU findings, placental serology and from later ultrasound examinations. Prenatal aneuploidy testing was performed by microarray, initially utilising array‐CGH, then SNP‐array for the last 2 years. Uniparental disomy studies were performed by SNP‐array for all 4 years. The majority of the NIPT tests were analysed using the Illumina platform, initially confined to assessment of the common autosomal and sex chromosome aneuploidies and extending to genome‐wide analysis for the last 2 years.ResultsAmniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 51% of whom had prior NIPT, with 612 (45%) returning a high‐risk result. The LTFU findings significantly altered the PPV of the NIPT result for trisomies 13, 18 and 21, monosomy X (MX) and rare autosomal trisomies (RATs), but not for the other sex chromosomal abnormalities or segmental imbalances (>7 Mb). An abnormal LFTU increased the PPV close to 100% for trisomies 13, 18 and 21, MX and RATs. The magnitude of the PPV alteration was highest for the lethal chromosomal abnormalities. If the LTFU was normal, the incidence of confined placental mosaicism (CPM) was highest for those with an original high risk T13 result, followed by T18, then T21. After a normal LFTU, the PPV for trisomies 21, 18, 13 and MX decreased to 68%, 57%, 5% and 25% respectively.ConclusionsLTFU after a high‐risk NIPT result can alter the PPV of many chromosomal abnormalities, assisting counselling regarding invasive prenatal testing and pregnancy management. The high PPV for trisomy 21 and 18 NIPT results are not sufficiently modified by normal LFTU findings to alter management and these patients should be offered a CVS for earlier diagnosis, particularly as there is a low rate of placental mosaicism with these aneuploidies. Patients with a high‐risk NIPT result for trisomy 13 and normal LFTU findings often await amniocentesis or avoid invasive testing altogether given the low PPV and higher rate of CPM in this context.This article is protected by copyright. All rights reserved.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Late first‐trimester ultrasound findings can alter management after high‐risk NIPT result

Scott,

Smet,

Elhindi

et al. 2023

Ultrasound in Obstet & Gyne

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“…4 The sensitivity and specificity of cell free fetal DNA (cffDNA) for SCAs are 80 to 90% on average and more than 99%, respectively. 4,5 Structural rearrangements and mosaicism for sex chromosomes are estimated to be 3% and 3 to 20% of SCA cases, respectively. 6 Mosaicism of monosomy X is present in 30 to 40% of Turner syndrome (TS) women and presents with a mild to moderate phenotype.…”

Section: Introductionmentioning

confidence: 99%

Detecting Mosaicism of Monosomy X Using FISH in Prenatal Samples: Post High Risk NIPT

Murarka,

Biswas,

Bhatt

et al. 2024

Journal of Fetal Medicine

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Noninvasive prenatal testing (NIPT) is a highly specific and sensitive aneuploidy screening method with low false positive results. Sex chromosome aneuploidy (SCA) is not picked up in prenatal ultrasounds, as they may not have antenatally identifiable features, except for hydrops in monosomy X cases. Women with high risk NIPT results for SCAs are recommended to go for invasive prenatal diagnosis for confirmation by diagnostic tests like chromosome microarray, karyotyping, and/or fluorescence in situ hybridization (FISH). We present two cases that showed a high risk for monosomy X on NIPT. Chromosomal microarray was negative for SCA. Further, FISH was done to confirm the results and confirm the presence of low level mosaicism for monosomy X. FISH proves to be the test of choice to detect low level mosaicism in high risk NIPT cases with high positive predictive values.

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“…As with other sex chromosome aneuploidies and pediatric rare conditions in general, our knowledge of TS is largely based on small single‐center studies challenged by multiple biases. With cell‐free DNA screening increasing prenatal identification, there is an ever‐growing need for generalizable research that informs best clinical practice and improves health outcomes for individuals with TS (Bussolaro et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a computable phenotype for Turner syndrome utilizing electronic health records from a national pediatric network

Huang,

Bamba,

Bothwell

et al. 2023

American J of Med Genetics Pt A

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Turner syndrome (TS) is a genetic condition occurring in ~1 in 2000 females characterized by the complete or partial absence of the second sex chromosome. TS research faces similar challenges to many other pediatric rare disease conditions, with homogenous, single‐center, underpowered studies. Secondary data analyses utilizing electronic health record (EHR) have the potential to address these limitations; however, an algorithm to accurately identify TS cases in EHR data is needed. We developed a computable phenotype to identify patients with TS using PEDSnet, a pediatric research network. This computable phenotype was validated through chart review; true positives and negatives and false positives and negatives were used to assess accuracy at both primary and external validation sites. The optimal algorithm consisted of the following criteria: female sex, ≥1 outpatient encounter, and ≥3 encounters with a diagnosis code that maps to TS, yielding an average sensitivity of 0.97, specificity of 0.88, and C‐statistic of 0.93 across all sites. The accuracy of any estradiol prescriptions yielded an average C‐statistic of 0.91 across sites and 0.80 for transdermal and oral formulations separately. PEDSnet and computable phenotyping are powerful tools in providing large, diverse samples to pragmatically study rare pediatric conditions like TS.

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The accuracy of prenatal cell-free DNA screening for sex chromosome abnormalities: A systematic review and meta-analysis

Cited by 8 publications

References 108 publications

Late first‐trimester ultrasound findings can alter management after high‐risk NIPT result

Late first‐trimester ultrasound findings can alter management after high‐risk NIPT result

Detecting Mosaicism of Monosomy X Using FISH in Prenatal Samples: Post High Risk NIPT

Development and validation of a computable phenotype for Turner syndrome utilizing electronic health records from a national pediatric network

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