Diagnostic Rates

Diagnostic Rates
Phenotypic indicationn=Diagnostic rate of pWES Author, Journal, yearLink to publication (full text may sit behind a paywall)
Links may need to be cut and paste link into new browser window
Nuchal Translucency >3.5mm at 11–14 weeks of gestation

213 1.8% - Isolated NT in first trimester (no other anomalies)

22% - non-isolated increased NT at presentation

32% - initially isolated increased NT with additional abnormalities detected later in pregnancy
Mellis, R., Eberhardt, R. Y., Hamilton, S. J., PAGE Consortium, McMullan, D. J., Kilby, M. D., ... & Chitty, L. S. (2021). Fetal exome sequencing for isolated increased nuchal translucency: Should we be doing it?. BJOG: An International Journal of Obstetrics & Gynaecology.https://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1111/1471-0528.16869
Non-immune hydrops fetalis (NIHF)
(systematic review data)
306 (meta analysis from 21 studies)29% - All NIHF

24% - Isolated NIHF

38% - NIHF associated with additional anomalies eg congenital limb contractures
Mone, F., Eberhardt, R. Y., Hurles, M. E., McMullan, D. J., Maher, E. R., Lord, J., Chitty, L. S., Dempsey, E., Homfray, T., Giordano, J. L., Wapner, R. J., Sun, L., Sparks, T. N., Norton, M. E., & Kilby, M. D. (2021). Fetal hydrops and the Incremental yield of Next generation sequencing over standard prenatal Diagnostic testing (FIND) study: prospective cohort study and meta-analysis. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 10.1002/uog.23652. Advance online publication. https://doi.org/10.1002/uog.23652
Also considers cohort data
Congenital heart disease (CHD)
(systematic review data)
636 (meta analysis from 18 studies)

21% - All CHD

11% - Isolated CHD

37% - CHD associated with extracardiac anomaly (eg genitourinary)
Mone, F., Eberhardt, R. Y., Morris, R. K., Hurles, M. E., McMullan, D. J., Maher, E. R., ... & Chung, B. H. Y. (2021). Congenital heart disease and the Diagnostic yield with Exome sequencing (CODE) study: prospective cohort study and systematic review. Ultrasound in Obstetrics & Gynecology, 57(1), 43-51.

Also considers cohort data
Non-immune hydrops fetalis (NIHF)12729%Sparks, T. N., Lianoglou, B. R., Adami, R. R., Pluym, I. D., Holliman, K., Duffy, J., Downum, S. L., Patel, S., Faubel, A., Boe, N. M., Field, N. T., Murphy, A., Laurent, L. C., Jolley, J., Uy, C., Slavotinek, A. M., Devine, P., Hodoglugil, U., Van Ziffle, J., Sanders, S. J., … University of California, San Francisco Center for Maternal–Fetal Precision Medicine (2020). Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis. The New England journal of medicine, 383(18), 1746–1756. https://doi.org/10.1056/NEJMoa2023643https://pubmed.ncbi.nlm.nih.gov/33027564/
Fetal structural anomalies (FSA)

6108.5% - FSA – all types

15.4% - Multiple FSA

11% - Cardiac

15% - Skeletal

3% - Isolated NT >4mm

Lord, J., McMullan, D. J., Eberhardt, R. Y., Rinck, G., Hamilton, S. J., Quinlan-Jones, E., Prigmore, E., Keelagher, R., Best, S. K., Carey, G. K., Mellis, R., Robart, S., Berry, I. R., Chandler, K. E., Cilliers, D., Cresswell, L., Edwards, S. L., Gardiner, C., Henderson, A., Holden, S. T., … Prenatal Assessment of Genomes and Exomes Consortium (2019). Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet (London, England), 393(10173), 747–757. https://doi.org/10.1016/S0140-6736(18)31940-8
Fetal structural anomalies (FSA)

23410% - FSA – all types

19% - Multiple FSA

5% - Cardiac

24% - Skeletal

12% - NT >4mm (not isolated)

24% - Lymphatic or effusion

16% - Renal

22% - CNS
Petrovski, S., Aggarwal, V., Giordano, J. L., Stosic, M., Wou, K., Bier, L., Spiegel, E., Brennan, K., Stong, N., Jobanputra, V., Ren, Z., Zhu, X., Mebane, C., Nahum, O., Wang, Q., Kamalakaran, S., Malone, C., Anyane-Yeboa, K., Miller, R., Levy, B., … Wapner, R. J. (2019). Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study. Lancet (London, England), 393(10173), 758–767. https://doi.org/10.1016/S0140-6736(18)32042-7
Fetal Structural Anomalies (systematic review of 34 studies - divided into two groups)

1840 (Meta analysis of 18 studies)

1421 (Meta analysis of 17 studies)

19% - Any structural anomaly, either associated or isolated

15% - Specific single class anomalies

Guadagnolo, D., Mastromoro, G., Di Palma, F., Pizzuti, A., & Marchionni, E. (2021). Prenatal Exome Sequencing: Background, Current Practice and Future Perspectives-A Systematic Review. Diagnostics (Basel, Switzerland), 11(2), 224. https://doi.org/10.3390/diagnostics11020224
Non-hydropic pleural effusions62

(54 isolated and 8 with additional anomalies)
13% (for unilateral isolated)Wellesley, D., & Howe, D. T. (2018). Diagnosis and outcome in nonhydropic fetal pleural effusions. Prenatal diagnosis, 38(11), 866-869.https://obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.5343
Recurrent fetal structural anomalies (similar anomalies in consecutive pregnancies) (Systematic Review of 9 studies)

14040%Pauta, M., Martinez-Portilla, R. J., & Borrell, A. (2021). Prenatal Exome Sequencing in Recurrent Fetal Structural Anomalies: Systematic Review and Meta-Analysis. Journal of clinical medicine, 10(20), 4739. https://doi.org/10.3390/jcm10204739https://pubmed.ncbi.nlm.nih.gov/34682862/
Multisystem fetal structural anomalies (systematic review of 17 studies) 69433%Pauta, M., Martinez‐Portilla, R. J., & Borrell, A. (2022). Diagnostic yield of exome sequencing in fetuses with multisystem malformations: systematic review and meta‐analysis. Ultrasound in Obstetrics & Gynecology.
Fetal anomalies500All - 38%

Skeletal – 52%

Complex (2+ FSAs) – 44%

Urogenital – 44%

Brain – 43%

NT >3mm – 33%

IUGR – 26%

Cardiac – 24%

Eye – 20%

Arthrogryposis - 20%

Internal organs – 19%

Other – 29%
Gabriel, H., Korinth, D., Ritthaler, M., Schulte, B., Battke, F., von Kaisenberg, C., ... & Biskup, S. (2021). Trio exome sequencing is highly relevant in prenatal diagnostics. Prenatal diagnosis.https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/pd.6081
Overview of issues arising from the use of Prenatal WES (quotes figures from Pitrovski and Lord studies outlined above) Mone F, McMullan DJ, Williams D, Chitty LS, Maher ER, Kilby MD; Fetal Genomics SteeringGroup of the British Society for Genetic Medicine; on behalf of the Royal College of Obstetricians and Gynaecologists.Evidence to Support the Clinical Utility of Prenatal Exome Sequencing in Evaluation of the Fetus with CongenitalAnomalies. Scientific Impact Paper No. 64. BJOG 2021;128:e39–e50.
CNS anomalies2687% (for single isolated CNS)

19% multiple CNS anomalies

16.7% CNS anomalies plus other anomaly

30% isolated agenesis of Corpus Collosum (n=10)
Baptiste, C., Mellis, R., Aggarwal, V., Lord, J., Eberhardt, R., Kilby, M. D., ... & Chitty, L. (2022). Fetal central nervous system anomalies: When should we offer exome sequencing?. Prenatal Diagnosis, 42(6), 736-743.https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/pd.6145
Corpus Collosum anomalies5034% - All collosal anomalies Lei, T. Y., She, Q., Fu, F., Zhen, L., Li, R., Yu, Q. X., ... & Liao, C. (2022). Prenatal exome sequencing in fetuses with callosal anomalies. Prenatal Diagnosis.https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/pd.6107
Fetal Structural anomalies4350 (Meta analysis of 66 studies)31% - FSA - all types

53% - Skeletal

37% Nueromuscular/ Fetal akinesia

29% Multisystem

22% hydrops/oedema

17% CNS


2% Isolated increased NT
Mellis, R., Oprych, K., Scotchman, E., Hill, M., & Chitty, L. S. (2022). Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: a systematic review and meta‐analysis. Prenatal Diagnosis.https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/pd.6115