Evidence map›Paper›PMID 34106556›Full record

Trial reportThe New England journal of medicine2021

Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia.

Jan A Deprest, Kypros H Nicolaides, Alexandra Benachi, Eduard Gratacos, Greg Ryan, Nicola Persico, Haruhiko Sago, Anthony Johnson, Mirosław Wielgoś, Christoph Berg and 3 more

3 registry-linked trialsAbstract readMulticenter StudyRandomized Controlled TrialEquivalence Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 135 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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.

NCT01240057 phase2 / phase3completednot on this map

Randomized Trial of Fetoscopic Endoluminal Tracheal Occlusion (FETO) Versus Expectant Management During Pregnancy in Fetuses With Left Sided and Isolated Congenital Diaphragma Hernia and Severe Pulmonary Hypoplasia.

TypeinterventionalSponsorUniversity Hospital, GasthuisbergRan2011 to 2020Enrolled93ConditionsCongenital Diseases, Diaphragmatic Hernia, Pulmonary HypoplasiaArmsfetal endoluminal tracheal occlusion, watchful waiting during pregnancy
NCT06281717 nawithdrawnnot on this mapstarted 2024, after this paper: background citation

A Pilot Study on the Role of Fetal Endotracheal Occlusion (FETO) in Fetuses With Severe Congenital Diaphragmatic Hernia

TypeinterventionalSponsorEyal KrispinRan2024 to 2031Enrolled0ConditionsCongenital Diaphragmatic HerniaArmsFetal Endotracheal Occlusion (FETO)
NCT06884423 narecruitingnot on this mapstarted 2025, after this paper: background citation

Infant Survival and Long-term Outcome Following Fetoscopic Endoluminal Tracheal Occlusion in Severe Left and Right Congenital Diaphragmatic Hernia, A Phase III Trial

TypeinterventionalSponsorHolly L Hedrick, MDRan2025 to 2032Enrolled80ConditionsCongenital Diaphragmatic Hernia, Pulmonary HypoplasiaArmsFETO with GoldBAL2 Balloon and BALTACCIBDPE100 Catheter
3 · Its place in the literature

Who cites it

135 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
  2. Benefits and complications of fetal and postnatal surgery for open spina bifida: systematic review and proportional meta-analysis.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2025
    Pooled it
  3. Pooled it
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  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Article
  10. Effect of right- vs left-sided congenital diaphragmatic hernia and duration of tracheal occlusion on longitudinal lung-size changes.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2026
    Observational
  11. Cervical length assessment using magnetic resonance imaging during pregnancy: correlation and agreement with transvaginal ultrasound.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2026
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Using simulation to prepare multidisciplinary teams and clinical environments for complex fetal interventions and resuscitation.Journal of perinatology : official journal of the California Perinatal Association · 2026
    Article
  20. Article

75 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Jan A DeprestFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).ORCID 0000-0002-4920-945X
Kypros H NicolaidesFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Alexandra BenachiFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Eduard GratacosFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Greg RyanFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Nicola PersicoFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Haruhiko SagoFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).ORCID 0000-0001-9387-1849
Anthony JohnsonFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Mirosław WielgośFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Christoph BergFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Ben Van CalsterFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
Francesca M RussoFrom the Department of Obstetrics and Gynecology, KU Leuven (J.A.D., F.M.R.) and Academic Department of Development and Regeneration, Biomedical Sciences, University Hospitals KU Leuven, Leuven, Belgium (J.A.D., B.V.C., F.M.R.); King's College Hospital (K.H.N.) and the Institute for Women's Health, University College London Hospital (J.A.D.) - both in London; Hospital Antoine-Béclère, Université Paris-Saclay, Clamart, France (A.B.); Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Mount Sinai Hospital, Toronto (G.R.); Hospital Maggiore Policlinico, Milan (N.P.); the National Center for Child Health and Development, Tokyo (H.S.); Children's Memorial Hermann Hospital, Houston (A.J.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and University Hospital Bonn, Bonn, Germany (C.B.).
TOTAL Trial for Severe Hypoplasia Investigators

Funding

Sixth Framework Programme EuroSTEC FP6-LIFESCIHEALTH CT 2006-37409Wellcome Trust 101957
6 · The paper itself

Abstract

backgroundObservational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking.

methodsIn this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women.

resultsThe trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P = 0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09).

conclusionsIn fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.).

Indexed as

Balloon OcclusionFetal TherapiesAdultFemaleFetoscopyGestational AgeHernias, Diaphragmatic, CongenitalHumansIntention to Treat AnalysisObstetric Labor, PrematurePatient AcuityPregnancyPremature BirthPremature Rupture of Fetal MembranesTracheaWatchful Waiting

Identifiers

PMID34106556
PMCPMC7613453

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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.