Prenatal Screening for Microdeletions and Rare Autosomal Aneuploidies20231130155929
Prenatal Screening for Microdeletions and Rare Autosomal Aneuploidies
Fiorentino D, Dar P.. Clin Obstet Gynecol. 2023;66(3):579-594. doi:10.1097/GRF.0000000000000799
Tags: Review / Meta-Analysis, 2023, International, RAAs, CNVs
- “Conclusion: To conclude, cfDNA is an attractive screening tool for chromosomal abnormalities that otherwise do not have dedicated screening modalities. However, the expansion of routine prenatal genetic screening to include rare syndromes has to balance patients’ desire for information about their pregnancy and the clinical utility of a screening test. Unfortunately, for many CNVs and RAAs, the clinical utility of this screening remains unclear. The principle of patient autonomy would dictate that these commercially available tests not be withheld from patients who desire greater information regarding their pregnancy, but detailed counseling is needed to ensure that the benefits and limitations of expanded cfDNA are clearly understood.”
Overview of Noninvasive Prenatal Testing (NIPT) for the Detection of Fetal Chromosome Abnormalities; Differences in Laboratory Methods and Scope of Testing.20231130155404
Overview of Noninvasive Prenatal Testing (NIPT) for the Detection of Fetal Chromosome Abnormalities; Differences in Laboratory Methods and Scope of Testing.
Benn P, Cuckle H. Clin Obstet Gynecol. 2023;66(3):536-556. doi:10.1097/GRF.0000000000000803.
Tags: Review / Meta-Analysis, 2023, International, RAAs, CNVs
- “Although nearly all noninvasive prenatal testing is currently based on analyzing circulating maternal cell-free DNA, the technical methods used vary considerably. We review the different methods. Based on validation trials and clinical experience, there are mostly relatively small differences in screening performance for trisomies 21, 18, and 13 in singleton pregnancies. Recent reports show low no-call rates for all methods, diminishing its importance when choosing a laboratory. However, method can be an important consideration for twin pregnancies, screening for sex chromosome abnormalities, microdeletion syndromes, triploidy, molar pregnancies, rare autosomal trisomies, and segmental imbalances, and detecting maternal chromosome abnormalities.”
Noninvasive prenatal testing: How far can we reach detecting fetal copy number variations.20221130164229
Noninvasive prenatal testing: How far can we reach detecting fetal copy number variations.
Mayo S, Gómez-Manjón I, Atencia G, Moreno-Izquierdo A, Escribano D, Fernández-Martínez FJ. Eur J Obstet Gynecol Reprod Biol. 2022;272:150-155. doi:10.1016/j.ejogrb.2022.03.027.
Tags: Case Report / Case Series, 2022, International, CNVs
- “We report a detection of 44.7 Mb duplication at 11p15.5-p11.2 by NIPT with a fetal fraction (FF) of only 3%. This chromosome abnormality was confirmed after amniocentesis by karyotyping and array comparative genomic hybridization on cultured fetal cells. Further parental investigation showed that the fetal chromosome abnormality was inherited from the mother who was a carrier of a balanced translocation 46,XX,t(11;X)(p11.2;q28). This case highlights the importance of expanded NIPT in the detection of fetal segmental aneuploidy. NIPT together with complementary studies can lead to the detection of parental chromosome rearrangement despite a low FF, which can impact the couple’s reproductive plans. We also reviewed other cases with chromosome rearrangement, detected by NIPT, derived from a parental reciprocal translocation.”
Genome wide noninvasive prenatal testing detects microduplication of the distal end of chromosome 15 in a fetus: a case report.20221130164153
Genome wide noninvasive prenatal testing detects microduplication of the distal end of chromosome 15 in a fetus: a case report.
Sahinbegovic H, Andres S, Langer-Freitag S, et al. Mol Cytogenet. 2022;15(1):16. Published 2022 Apr 2. doi:10.1186/s13039-022-00592-3. Open Access: Learn more
Tags: Case Report / Case Series, 2022, International, CNVs
- NIPT detected a 10.34 Mb terminal 15q dup (15q26.1q26.3), subsequently confirmed using karyotype, microarray, and FISH (fluorescence in situ hybridization). Karyotype results indicated an unbalanced translocation between chromosomes 15 and 18 with a final karyotype of 46,XX,der(18)t(15;18)(q26.2;q23)dn.
Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies20221130164003
Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies
[published correction appears in Genet Med. 2022 Sep;24(9):1992]. Rose NC, Barrie ES, Malinowski J, et al. Genet Med. 2022;24(7):1379-1391. doi:10.1016/j.gim.2022.03.019. Open Access: Learn more
Tags: Review, 2022, International, RAAs, CNVs
- 87 studies met inclusion criteria for this systematic evidence review, evaluating NIPT performance in a general-risk population.
- Performance for RATs and CNVs was variable and poorer than for common trisomies. For RATs, this is likely related to the rarity of RATs and insufficient data to develop a method that can distinguish between clinically significant RATs present in the fetus versus CPM.
- “Reported overall sensitivity to detect CNVs ranged from 69.44% to 80.56%. When stratified by CNV size, in general, the sensitivity to detect larger CNVs was better than for detecting smaller CNVs. The sensitivity to detect CNVs larger than 5 megabases (Mb) was >90%, whereas for those smaller than 5 Mb, it was 68.42%.”
- NIPT is the only laboratory-based prenatal screen that can identify SCAs, RATs, and CNVs.
Rare autosomal trisomies detected by non-invasive prenatal testing: an overview of current knowledge.20221130163755
Rare autosomal trisomies detected by non-invasive prenatal testing: an overview of current knowledge.
Lannoo L, van Straaten K, Breckpot J, et al. Eur J Hum Genet. 2022;30(12):1323-1330. doi:10.1038/s41431-022-01147-1.
Tags: Review / Meta-Analysis, 2022, International, RAAs
- “In this review we reviewed the current knowledge of the most common RATs. We compiled clinical relevant parameters such as incidence, meiotic or mitotic origin, the risk of fetal (mosaic) aneuploidy, clinical manifestations of fetal mosaicism for a RAT, the effect of confined placental mosaicism on placental function and the risk of uniparental disomy (UPD). Finally, we identified gaps in the knowledge on RATs and highlight areas of future research. This overview may serve as a first guide for prenatal management for each of these RATs.”
Validity and Utility of Non-Invasive Prenatal Testing for Copy Number Variations and Microdeletions: A Systematic Review.20221130163533
Validity and Utility of Non-Invasive Prenatal Testing for Copy Number Variations and Microdeletions: A Systematic Review.
Zaninović L, Bašković M, Ježek D, Katušić Bojanac A. J Clin Med. 2022;11(12):3350. Published 2022 Jun 10. doi:10.3390/jcm11123350. Open Access: Learn more
Tags: Review / Meta-Analysis, 2022, International, CNVs
- 32 articles met the criteria for this systematic review of the analytical and clinical performance of NIPT for CNVs and microdeletions.
- “The reported sensitivity of the applied tests ranged from 20% to 100%, the specificity from 81.62% to 100%, and the PPV from 3% to 100% for cases with diagnostic or clinical follow-up information. No confirmatory analysis was available in the majority of cases with negative screening results, and, therefore, the NPVs [negative predictive values] could not be determined.”
The predictive value of prenatal cell-free DNA testing for rare autosomal trisomies: a systematic review and meta-analysis.20221130163223
The predictive value of prenatal cell-free DNA testing for rare autosomal trisomies: a systematic review and meta-analysis.
Acreman ML, Bussolaro S, Raymond YC, Fantasia I, Rolnik DL, Da Silva Costa F. Am J Obstet Gynecol. 2023;228(3):292-305.e6. doi:10.1016/j.ajog.2022.08.034.
Tags: Review / Meta-Analysis, 2022, International, RAAs
- Systematic review and meta-analysis to determine the PPV of cfDNA screening for RATs. 31 studies, representing 1703 women were included.
- Pooled PPV for RATs was 11.46%. Statistical heterogeneity was high. Insufficient data to provide accurate ascertainment of sensitivity and specificity because Confirmatory testing was mostly only offered to women with high-risk results; therefore, there was insufficient data to determine sensitivity and specificity.
Multisite assessment of the impact of cell-free DNA-based screening for rare autosomal aneuploidies on pregnancy management and outcomes.20221130163126
Multisite assessment of the impact of cell-free DNA-based screening for rare autosomal aneuploidies on pregnancy management and outcomes.
Mossfield T, Soster E, Menezes M, et al. Front Genet. 2022;13:975987. Published 2022 Aug 29. doi:10.3389/fgene.2022.975987. Open Access: Learn more
Tags: Clinical Experience / Clinical Utility, 2022, International, RAAs, Consortium Publication
- “Here, we describe a multi-cohort, global retrospective study that looked at the clinical outcomes of cases with a high-risk cfDNA screening result for a RAA. Our study cohort included a total of 109 cases from five different sites, with diagnostic outcome information available for 68% (74/109) of patients. Based on confirmatory diagnostic testing, we found a concordance rate of 20.3% for presence of a RAA (15/74) in our study population. Pregnancy outcome was also available for 77% (84/109) of cases in our cohort. Many of the patients experienced adverse pregnancy outcomes, including intrauterine fetal demise, fetal growth restriction, and preterm birth. These adverse outcomes were observed both in patients with fetal or placental confirmation of the presence of a RAA, as well as patients that did not undergo fetal and/or placental diagnostic testing.”
- “In addition, we have proposed some suggestions for pregnancy management and counseling considerations for situations where a RAA is noted on a cfDNA screen.”
- “In conclusion, our study has shown that genome-wide cfDNA screening for the presence of rare autosomal aneuploidies can be beneficial for both patients and their healthcare practitioners. This can provide a possible explanation for an adverse pregnancy outcome or result in a change in pregnancy management, such as increased monitoring for adverse outcomes.”
Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?20211130174703
Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?
Mardy AH, Norton ME. Prenat Diagn. 2021;41(10):1249-1254. doi:10.1002/pd.6021.
Tags: Review / Meta-Analysis, 2021, International, RAAs
- Review of the literature to provide recommendations on chorionic villus sampling (CVS) versus amniocentesis after a positive NIPT result for autosomal aneuploidies, monosomy X, and multiple aneuploidies.
- “Conclusion: Clinicians should consider rates of CPM, imprinting, ultrasound findings and maternal factors when considering whether to recommend amnio or CVS after an abnormal cfDNA result.”