Evidence map›Paper›PMID 37758840›Full record

ArticleCommunications medicine2023

Genetic and clinical variables act synergistically to impact neurodevelopmental outcomes in children with single ventricle heart disease.

Thomas A Miller, Edgar J Hernandez, J William Gaynor, Mark W Russell, Jane W Newburger, Wendy Chung, Elizabeth Goldmuntz, James F Cnota, Sinai C Zyblewski, William T Mahle and 13 more

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In one paragraph

Article in Communications medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Observational
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Thomas A Miller *Department of Pediatrics, Maine Medical Center, Portland, ME, USA. Thomas.A.Miller@mainehealth.org.
Edgar J Hernandez *Department of Human Genetics and Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT, USA.
J William GaynorDepartment of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mark W RussellDepartment of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Jane W NewburgerDepartment of Cardiology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7794-9017
Wendy ChungDepartments of Pediatrics and Medicine, Columbia University, New York, NY, USA.
Elizabeth GoldmuntzDivision of Cardiology, Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
James F CnotaHeart Institute, Cincinnati Children's Hospital, Cincinnati, OH, USA.
Sinai C ZyblewskiDepartment of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
William T MahleChildren's Healthcare of Atlanta, Atlanta, GA, USA.
Victor ZakHealthcore, Watertown, MA, USA.
Chitra RavishankarDivision of Cardiology, Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jonathan R KaltmanDivision of Cardiology, Children's National Hospital, Washington, DC, USA.
Brian W McCrindleLabatt Family Heart Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
Shanelle ClarkeDepartment of Pediatrics Emory University School of Medicine, Atlanta, GA, USA.
Jodie K Votava-SmithDepartment of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Eric M GrahamDepartment of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
Mike SeedLabatt Family Heart Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-7330-234X
Nancy RuddDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Daniel BernsteinStanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7761-5853
Teresa M LeeDepartments of Pediatrics and Medicine, Columbia University, New York, NY, USA.
Mark YandellDepartment of Human Genetics and Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT, USA. myandell@genetics.utah.edu.ORCID http://orcid.org/0000-0002-9497-4505
Martin Tristani-FirouziDepartment of Pediatrics, University of Utah, Salt Lake City, UT, USA. Martin.Tristani@utah.edu.ORCID http://orcid.org/0000-0001-5916-442X

Funding

Administrative Coordinating Center: Cardiovascular Development and Pediatric Cardiac Genomics ConsortiaU01HL131003 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI CNOTA, JAMES, OLLBERDING, NICHOLAS J · 2016 to 2024
$54.8M
Pediatric Heart network DCCU10HL068270 · NHLBI · NEW ENGLAND RESEARCH INSTITUTES, INC. · PI MILLER, JULIE ELAINE, TRACHTENBERG, FELICIA LYNN · 2011 to 2016
$44.9M
Ventricular Volumes and Varability (VVV)U01HL068270 · NHLBI · NEW ENGLAND RESEARCH INSTITUTES, INC. · PI SLEEPER, LYNN A · 2001 to 2010
$40.3M
CTSA UM1 Program at University of UtahUM1TR004409 · NCATS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI RACHEL HESS, Jennifer Juhl Majersik · 2023 to 2026
$21.9M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
The Genetic Basis of Conotruncal DefectsU01HL098153 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI GOLDMUNTZ, ELIZABETH · 2009 to 2014
$4.3M
Pediatric Heart Network: Follow-up of the Single Ventricle Reconstruction TrialU01HL068290 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LAI, WYMAN W · 2001 to 2010
$4.1M
Molecular approaches to gene identification in congenital heart diseaseU01HL098163 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CHUNG, WENDY K, WARBURTON, DOROTHY P. · 2009 to 2014
$3.9M
Pediatric Heart Disease Network: CHOP MembershipU01HL068279 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI VETTER, VICTORIA L · 2001 to 2010
$3.7M
Randomized Therapeutic Trials in Pediatric Heart DiseaseU01HL068285 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI NEWBURGER, JANE W. · 2001 to 2010
$3.4M
Randomized Clinical Trials for Pediatric Heart DiseaseU01HL068281 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI SAUL, J PHILIP · 2001 to 2010
$3.2M
Clinical and genomic responses to remote ischemic preconditioningU01HL068288 · NHLBI · HOSPITAL FOR SICK CHLDRN (TORONTO) · PI MCCRINDLE, BRIAN W · 2001 to 2010
$3.0M
NCATS NIH HHS UM1 TR004409NHLBI NIH HHS U01 HL068269NHLBI NIH HHS U01 HL068270NHLBI NIH HHS U01 HL068279NHLBI NIH HHS U01 HL068281NHLBI NIH HHS U01 HL068285NHLBI NIH HHS U01 HL068288NHLBI NIH HHS U01 HL068290NHLBI NIH HHS U01 HL068292NHLBI NIH HHS U01 HL085057NHLBI NIH HHS U01 HL098153NHLBI NIH HHS U01 HL098163NHLBI NIH HHS U01 HL128711NHLBI NIH HHS U01 HL131003NHLBI NIH HHS U10 HL068270NHLBI NIH HHS UM1 HL098123NHLBI NIH HHS UM1 HL098147NHLBI NIH HHS UM1 HL098162NHLBI NIH HHS UM1 HL128711NHLBI NIH HHS UM1 HL128761NICHD NIH HHS P50 HD105351NIGMS NIH HHS R01 GM104390NIH HHS S10 OD021644
6 · The paper itself

Abstract

backgroundRecent large-scale sequencing efforts have shed light on the genetic contribution to the etiology of congenital heart defects (CHD); however, the relative impact of genetics on clinical outcomes remains less understood. Outcomes analyses using genetics are complicated by the intrinsic severity of the CHD lesion and interactions with conditionally dependent clinical variables.

methodsBayesian Networks were applied to describe the intertwined relationships between clinical variables, demography, and genetics in a cohort of children with single ventricle CHD.

resultsAs isolated variables, a damaging genetic variant in a gene related to abnormal heart morphology and prolonged ventilator support following stage I palliative surgery increase the probability of having a low Mental Developmental Index (MDI) score at 14 months of age by 1.9- and 5.8-fold, respectively. However, in combination, these variables act synergistically to further increase the probability of a low MDI score by 10-fold. The absence of a damaging variant in a known syndromic CHD gene and a shorter post-operative ventilator support increase the probability of a normal MDI score 1.7- and 2.4-fold, respectively, but in combination increase the probability of a good outcome by 59-fold.

conclusionsOur analyses suggest a modest genetic contribution to neurodevelopmental outcomes as isolated variables, similar to known clinical predictors. By contrast, genetic, demographic, and clinical variables interact synergistically to markedly impact clinical outcomes. These findings underscore the importance of capturing and quantifying the impact of damaging genomic variants in the context of multiple, conditionally dependent variables, such as pre- and post-operative factors, and demography.

Identifiers

PMID37758840
PMCPMC10533527

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