Dataset Information

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

ABSTRACT:

Background

Recent 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.

Methods

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

Results

As 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.

Conclusions

Our 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.

SUBMITTER: Miller TA

PROVIDER: S-EPMC10533527 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Miller Thomas A TA Hernandez Edgar J EJ Gaynor J William JW Russell Mark W MW Newburger Jane W JW Chung Wendy W Goldmuntz Elizabeth E Cnota James F JF Zyblewski Sinai C SC Mahle William T WT Zak Victor V Ravishankar Chitra C Kaltman Jonathan R JR McCrindle Brian W BW Clarke Shanelle S Votava-Smith Jodie K JK Graham Eric M EM Seed Mike M Rudd Nancy N Bernstein Daniel D Lee Teresa M TM Yandell Mark M Tristani-Firouzi Martin M

Communications medicine 20230927 1

<h4>Background</h4>Recent 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.<h4>Methods</h4>Bayesian Networks were applied to describe the intertwined relationships between clinic ...[more]

PMID: 37758840

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Project description:Background The impact of neighborhood socioeconomic status (SES) on outcomes following first-stage palliation of single ventricle heart disease remains incompletely characterized. Methods and Results This was a single-center, retrospective review of consecutive patients who underwent the Norwood procedure from January 1, 1997 to November 11, 2017. Outcomes of interest included in-hospital (early) mortality or transplant, postoperative hospital length-of-stay, inpatient cost, and postdischarge (late) mortality or transplant. The primary exposure was neighborhood SES, assessed using a composite score derived from 6 US census-block group measures related to wealth, income, education, and occupation. Associations between SES and outcomes were assessed using logistic regression, generalized linear, or Cox proportional hazards models, adjusting for baseline patient-related risk factors. Of 478 patients, there were 62 (13.0%) early deaths or transplants. Among 416 transplant-free survivors at hospital discharge, median postoperative hospital length-of-stay and cost were 24 (interquartile range, 15-43) days and $295 000 (interquartile range, $193 000-$563 000), respectively. There were 97 (23.3%) late deaths or transplants. On multivariable analysis, patients in the lowest SES tertile had greater risk of early mortality or transplant (odds ratio [OR], 4.3 [95% CI, 2.0-9.4; P<0.001]), had longer hospitalizations (coefficient 0.4 [95% CI, 0.2-0.5; P<0.001]), incurred higher costs (coefficient 0.5 [95% CI, 0.3-0.7; P<0.001]), and had greater risk of late mortality or transplant (hazard ratio, 2.2 [95% CI, 1.3-3.7; P=0.004]), compared with those in the highest tertile. The risk of late mortality was partially attenuated with successful completion of home monitoring programs. Conclusions Lower neighborhood SES is associated with worse transplant-free survival following the Norwood operation. This risk persists throughout the first decade of life and may be mitigated with successful completion of interstage surveillance programs.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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