Evidence map›Paper›PMID 33027564›Full record

ArticleThe New England journal of medicine2020

Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis.

Teresa N Sparks, Billie R Lianoglou, Rebecca R Adami, Ilina D Pluym, Kerry Holliman, Jennifer Duffy, Sarah L Downum, Sachi Patel, Amanda Faubel, Nina M Boe and 14 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03412760 (Hydrops), which is not on this map. Cited by 99 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 5 pooled it
3.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03412760 naactive not recruitingnot on this map

Hydrops: Diagnosing & Redefining Outcomes With Precision Study

TypeinterventionalSponsorUniversity of California, San FranciscoRan2018 to 2027Enrolled500ConditionsHydrops Fetalis, Birth Defect, Fetal AnomalyArmsExome sequencing
3 · Its place in the literature

Who cites it

99 citing papers in PubMed, 5 syntheses or guidelines pooled it, 185 citations in OpenAlex.

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  5. 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 · 2021
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  17. Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
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39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 4 institutions in 1 country.

Teresa N SparksFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).ORCID 0000-0002-8593-2186
Billie R LianoglouFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Rebecca R AdamiFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Ilina D PluymFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).ORCID 0000-0003-4891-3354
Kerry HollimanFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Jennifer DuffyFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Sarah L DownumFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Sachi PatelFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Amanda FaubelFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Nina M BoeFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Nancy T FieldFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Aisling MurphyFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Louise C LaurentFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Jennifer JolleyFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Cherry UyFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Anne M SlavotinekFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Patrick DevineFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Ugur HodoglugilFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Jessica Van ZiffleFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Stephan J SandersFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Tippi C MacKenzieFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
Mary E NortonFrom the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).
University of California Fetal–Maternal Consortium
University of California, San Francisco Center for Maternal–Fetal Precision Medicine
University of California, San Francisco · USUniversity of California System · USUniversity of California, Irvine · USUniversity of California, Los Angeles · US

Funding

Sharing Aggregate Genomics Research Findings with Diverse Participants: A Pilot Study of an Innovative Design StrategyU01HG009599 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOENIG, BARBARA A., KWOK, PUI-YAN · 2017 to 2021
$16.3M
WOMEN'S REPRODUCTIVE HEALTH RESEARCH CENTERK12HD001262 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Andrea Vashti Jackson · 1998 to 2026
$9.3M
Fetal Health Foundation N/ANational Institute of Child Health and Human Development 5K12HD001262-18NHGRI NIH HHS U01 HG 009599NHGRI NIH HHS U01 HG009599NICHD NIH HHS K12 HD001262United States N/A
6 · The paper itself

Abstract

backgroundThe cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear.

methodsWe evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited.

resultsIn 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases.

conclusionsIn this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.).

Indexed as

Exome SequencingGenetic VariationPrenatal DiagnosisFemaleHumansHydrops FetalisPregnancyPrognosis

Identifiers

PMID33027564
PMCPMC7650529
OpenAlexW3091850289

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.