Causes of Death in Infants and Children with Congenital Heart Disease

Williams, Jason A.; Török, Rachel D.; D’Ottavio, Alfred; Spears, Tracy; Chiswell, Karen; Forestieri, Nina; Sang, Charlie J.; Paolillo, Joseph; Walsh, Michael J.; Hoffman, Timothy M.; Kemper, Alex R.; Li, Jennifer S.

doi:10.1007/s00246-021-02612-2

Cited by 10 publications

(8 citation statements)

References 32 publications

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“…A recent study investigating causes of death in infants, children and young adults up to 20 years old with CHD found that the primary cause of mortality in infants was CHD, followed by lung disease and infection. In children, the leading causes were CHD, neurological disease and infection 27. The absence of cancer in this report likely reflects its relatively low incidence of cancer-related death in paediatric patients compared with adults.…”

Section: Discussionmentioning

confidence: 66%

Outcomes after cancer diagnosis in children and adult patients with congenital heart disease in Sweden: a registry-based cohort study

Karazisi,

Dellborg,

Mellgren

et al. 2024

BMJ Open

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ObjectivePatients with congenital heart disease (CHD) have an increased cancer risk. The aim of this study was to determine cancer-related mortality in CHD patients compared with non-CHD controls, compare ages at cancer diagnosis and death, and explore the most fatal cancer diagnoses.DesignRegistry-based cohort study.Setting and participantsCHD patients born between 1970 and 2017 were identified using Swedish Health Registers. Each was matched by birth year and sex with 10 non-CHD controls. Included were those born in Sweden with a cancer diagnosis.ResultsCancer developed in 758 out of 67814 CHD patients (1.1%), with 139 deaths (18.3%)—of which 41 deaths occurred in patients with genetic syndromes. Cancer was the cause of death in 71.9% of cases. Across all CHD patients, cancer accounted for 1.8% of deaths. Excluding patients with genetic syndromes and transplant recipients, mortality risk between CHD patients with cancer and controls showed no significant difference (adjusted HR 1.17; 95% CI 0.93 to 1.49). CHD patients had a lower median age at cancer diagnosis—13.0 years (IQR 2.9–30.0) in CHD versus 24.6 years (IQR 8.6–35.1) in controls. Median age at death was 15.1 years (IQR 3.6–30.7) in CHD patients versus 18.5 years (IQR 6.1–32.7) in controls. The top three fatal cancer diagnoses were ill-defined, secondary and unspecified, eye and central nervous system tumours and haematological malignancies.ConclusionsCancer-related deaths constituted 1.8% of all mortalities across all CHD patients. Among CHD patients with cancer, 18.3% died, with cancer being the cause in 71.9% of cases. Although CHD patients have an increased cancer risk, their mortality risk post-diagnosis does not significantly differ from non-CHD patients after adjustements and exclusion of patients with genetic syndromes and transplant recipients. However, CHD patients with genetic syndromes and concurrent cancer appear to be a vulnerable group.

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Section: Discussionmentioning

confidence: 66%

Outcomes after cancer diagnosis in children and adult patients with congenital heart disease in Sweden: a registry-based cohort study

Karazisi,

Dellborg,

Mellgren

et al. 2024

BMJ Open

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“…Congenital heart disease (CHD) is one of the leading causes of death in newborns 103 . Several models that mimic the heart have been made to recapitulate aspects of cardiogenesis 104 – 108 ; however, to fully understand the dynamics of heart development, observing the organ alone is insufficient.…”

Section: Modeling Congenital Diseases Using Synthetic Embryosmentioning

confidence: 99%

A new era of stem cell and developmental biology: from blastoids to synthetic embryos and beyond

Kim,

Shin

2023

Exp Mol Med

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Recent discoveries in stem cell and developmental biology have introduced a new era marked by the generation of in vitro models that recapitulate early mammalian development, providing unprecedented opportunities for extensive research in embryogenesis. Here, we present an overview of current techniques that model early mammalian embryogenesis, specifically noting models created from stem cells derived from two significant species: Homo sapiens, for its high relevance, and Mus musculus, a historically common and technically advanced model organism. We aim to provide a holistic understanding of these in vitro models by tracing the historical background of the progress made in stem cell biology and discussing the fundamental underlying principles. At each developmental stage, we present corresponding in vitro models that recapitulate the in vivo embryo and further discuss how these models may be used to model diseases. Through a discussion of these models as well as their potential applications and future challenges, we hope to demonstrate how these innovative advances in stem cell research may be further developed to actualize a model to be used in clinical practice.

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“…Congenital heart disease (CHD) is the most common congenital malformations in newborns, and it remains the leading cause of mortality among infants under one year old [1]. CHD consists of a cluster of structural abnormalities, ranging from insignificant defects to complex life-threatening malformations.…”

Section: Introductionmentioning

confidence: 99%

TGFBR1 Variants Can Associate with Non-Syndromic Congenital Heart Disease without Aortopathy

Alaamery,

Albesher,

Alhabshan

et al. 2023

JCDD

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Background: Congenital heart diseases (CHD) are the most common congenital malformations in newborns and remain the leading cause of mortality among infants under one year old. Molecular diagnosis is crucial to evaluate the recurrence risk and to address future prenatal diagnosis. Here, we describe two families with various forms of inherited non-syndromic CHD and the genetic work-up and resultant findings. Methods: Next-generation sequencing (NGS) was employed in both families to uncover the genetic cause. In addition, we performed functional analysis to investigate the consequences of the identified variants in vitro. Results: NGS identified possible causative variants in both families in the protein kinase domain of the TGFBR1 gene. These variants occurred on the same amino acid, but resulted in differently substituted amino acids (p.R398C/p.R398H). Both variants co-segregate with the disease, are extremely rare or unique, and occur in an evolutionary highly conserved domain of the protein. Furthermore, both variants demonstrated a significantly altered TGFBR1-smad signaling activity. Clinical investigation revealed that none of the carriers had (signs of) aortopathy. Conclusion: In conclusion, we describe two families, with various forms of inherited non-syndromic CHD without aortopathies, associated with unique/rare variants in TGFBR1 that display altered TGF-beta signaling. These findings highlight involvement of TGFBR1 in CHD, and warrant consideration of potential causative TGFBR1 variants also in CHD patients without aortopathies.

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Causes of Death in Infants and Children with Congenital Heart Disease

Cited by 10 publications

References 32 publications

Outcomes after cancer diagnosis in children and adult patients with congenital heart disease in Sweden: a registry-based cohort study

Outcomes after cancer diagnosis in children and adult patients with congenital heart disease in Sweden: a registry-based cohort study

A new era of stem cell and developmental biology: from blastoids to synthetic embryos and beyond

TGFBR1 Variants Can Associate with Non-Syndromic Congenital Heart Disease without Aortopathy

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