| Title: |
Fetal hydrops and the Incremental yield of Next‐generation sequencing over standard prenatal Diagnostic testing ( FIND) study: prospective cohort study and meta‐analysis |
| Authors: |
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. |
| Source: |
Ultrasound in Obstetrics & Gynecology ; volume 58, issue 4, page 509-518 ; ISSN 0960-7692 1469-0705 |
| Publisher Information: |
Wiley |
| Publication Year: |
2021 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Objective To determine the incremental yield of exome sequencing (ES) over chromosomal microarray analysis (CMA) or karyotyping in prenatally diagnosed non‐immune hydrops fetalis (NIHF). Methods A prospective cohort study (comprising an extended group of the Prenatal Assessment of Genomes and Exomes (PAGE) study) was performed which included 28 cases of prenatally diagnosed NIHF undergoing trio ES following negative CMA or karyotyping. These cases were combined with data from a systematic review of the literature. MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched electronically (January 2000 to October 2020) for studies reporting on the incremental yield of ES over CMA or karyotyping in fetuses with prenatally detected NIHF. Inclusion criteria for the systematic review were: (i) at least two cases of NIHF undergoing sequencing; (ii) testing initiated based on prenatal ultrasound‐based phenotype; and (iii) negative CMA or karyotyping result. The incremental diagnostic yield of ES was assessed in: (i) all cases of NIHF; (ii) isolated NIHF; (iii) NIHF associated with an additional fetal structural anomaly; and (iv) NIHF according to severity (i.e. two vs three or more cavities affected). Results In the extended PAGE study cohort, the additional diagnostic yield of ES over CMA or karyotyping was 25.0% (7/28) in all NIHF cases, 21.4% (3/14) in those with isolated NIHF and 28.6% (4/14) in those with non‐isolated NIHF. In the meta‐analysis, the pooled incremental yield based on 21 studies (306 cases) was 29% (95% CI, 24–34%; P < 0.00001; I 2 = 0%) in all NIHF, 21% (95% CI, 13–30%; P < 0.00001; I 2 = 0%) in isolated NIHF and 39% (95% CI, 30–49%; P < 0.00001; I 2 = 1%) in NIHF associated with an additional fetal structural anomaly. In the latter group, congenital limb contractures were the most prevalent additional structural anomaly associated with a causative pathogenic variant, occurring in 17.3% (19/110) of cases. The incremental yield did not differ significantly according to ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/uog.23652 |
| Availability: |
https://doi.org/10.1002/uog.23652; https://onlinelibrary.wiley.com/doi/pdf/10.1002/uog.23652; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/uog.23652; https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1002/uog.23652 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.D0703998 |
| Database: |
BASE |