Many childhood-onset diseases used to be lethal. Improved life expectancy yield that most patients can survive into adulthood, to date. However, survivors of childhood-onset diseases often develop morbidities that suggest accelerated aging. Indeed, age-related conditions are observed sooner and more frequently in people with childhood-onset diseases. Congenital heart disease (CHD) is a typical example of a childhood-onset disease and is the most common birth defect, comprising a spectrum of mild, moderate and complex heart defects. Recent studies showed that age-related morbidities occur more often and at an earlier age in these patients. The overall goal of this project is to quantify and understand disparities in chronological and biological age over the lifespan in CHD patients.

Three main research objectives are proposed:

Objective 1: The investigators will determine the biological age in patients with CHD across the lifespan, using established and novel biomarkers for aging, and assess the disparity with chronological age.

Objective 2: The investigators will identify clinical, behavioral, psychological and social predictors of aging in patients with CHD.

Objective 3: The investigators will investigate the difference in biological-chronological age disparity between patients with CHD and healthy counterparts.

Three studies will be performed to investigate these objectives:

Study 1: Newborns with CHD

- The aim is to (i) compare telomere length in newborns with or without CHD; and (ii) to assess pregnancy-related/clinical and mother-related (behavioral, psychological, social) predictors of telomere length in newborns with CHD.

Study 2: (Young) adults with CHD

- This study aims to (i) compare telomere length in age strata of (young) adults with or without CHD; (ii) to assess clinical, behavioral, psychological, and social predictors of telomere length in patients with CHD; and (iii) to explore the relationship with functional outcomes, such as frailty and cognition.

Study 3: Epigenetic clock in adults with CHD

- This study focusses on (i) assessing the biological age by measuring DNA methylation in mild, moderate and complex heart defects, and (ii) determining if the disparity between biological and chronological age is a function of anatomical complexity and functional status of the patients and (iii) comparing the epigenetic clock of adults with and without CHD.

1. Newborn with CHD and mother

   Inclusion:

   • Newborns with CHD who are diagnosed and born in UZ Leuven or UZ Gent
   • The mother is able to adequate fill out the questionnaires
   • Informed consent is signed

   Exclusion:

   • The mother does not speak Dutch
   • The heart defect falls within a syndrome condition (e.g., Down syndrome, 22q11 deletion)
   • Very mild heart defects such as a patent foramen ovale, an open ductus of Botalli (no intervention needed), spontaneous closure of ASD/VSD, an isolated mild peripheral pulmonary stenosis

2. Adults with CHD - study 2

   Inclusion:

   • ≥ 18 years of age at the moment of study inclusion
   • Diagnosed with CHD
   • Follow-up at the UZ Leuven or UZ Gent
   • Signed informed consent
   • Physical, cognitive, and language abilities to complete self-report questionnaires/ assessment tests

   Exclusion:

   • Not speaking Dutch
   • Very mild heart defects such as a patent foramen ovale, an open ductus of Botalli (no intervention needed), spontaneous closure of ASD/VSD, an isolated mild peripheral pulmonary stenosis
   • The heart defect falls within a syndrome condition (e.g., Down syndrome, 22q11 deletion)

3. Adults with CHD - study 3

   Inclusion:

   • Included in study 2
   • Between 30-50 years of age at the moment of study inclusion
   • Follow-up at the UZ Leuven or UZ Gent
   • Signed informed consent
   • Physical, cognitive, and language abilities to complete self-report questionnaires/ assessment tests
   • Having one of the following CHD conditions: isolated arterial septal defect, isolated ventricular septal defect, tetralogy of Fallot, coarctation of the aorta, Fontan operation or systemic right ventricle.

   Exclusion

   • Not speaking Dutch
   • The heart defect falls within a syndrome condition (e.g., Downsyndrome, 22q11 deletion)

4. Health volunteers

Inclusion:

• Male or female healthy volunteers of the Red Cross
• Aged 18 - 65 years at the moment of inclusion
• The healthy volunteers must match with the patients included in study 2 based on age and sex
• Signed informed consent
• The requirements of the Red Cross for blood donation are fulfilled

Exclusion:

• Medical history of cardiac, pulmonal, renal or liver disease, chronic anemia, blood clotting disorder
• Not speaking Dutch
• Pregnancy
• Born with a heart condition

1. Newborns with CHD and mother
2. Adults with CHD - study 2 For each age stratum 100 patients must be included (Gent and Leuven combined), so a total of 500 patients will be included: 18-24 years of age, 25-34 years of age, 35-44 years of age, 45-54 years of age, ≥ 55 years of age
3. Adults with CHD - study 3 These patients must also be included in study 2. The patients must have the following CHD conditions: isolated arterial septal defect, isolated ventricular septal defect, tetralogy of Fallot, coarctation of the aorta, Fontan operation or systemic right ventricle. Furthermore, they need to be between 30-50 years old.
4. Healthy volunteers Health volunteers of the Red Cross.