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.”
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.
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.”
Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations.20211130174255

Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations.

Wang J, Zhang B, Zhou L, Zhou Q, Chen Y, Yu B. Front Genet. 2021;12:665589. Published 2021 Jul 16. doi:10.3389/fgene.2021.665589. Open Access: Learn more

Tags: Clinical Experience / Clinical Utility, Review / Meta-Analysis, 2021, International, CNVs

  • “Among the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%.”
  • “10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10-97.70% and the PPVs were 36.11-80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs > 3 Mb.”