Complex Congenital Heart Disease Linked to Increased Early-Life Stress


Children with heart disease who received infant open-heart surgery had more stress and neurodevelopmental impairments compared with children who did not undergo surgery.

Early adolescents with complex congenital heart disease (cCHD) are more stressed than healthy adolescents, according to investigators who recently published the results of a case-control study in JAMA Network Open. These children had higher concentrations of cortisol and cortisone, which can have deleterious effects on brain structure and brain function.

Image credit: Satjawat |

Image credit: Satjawat |

“Alterations of the physiological stress system in patients with cCHD may drive neurodevelopmental impairments, particularly poorer [executive function] performance,” wrote authors in the paper.

Patients with cCHD often undergo cardiac surgeries or other interventions as infants to manage the condition. This can cause heightened and prolonged stress that affects the child throughout their developmental years. Some studies have found that high stress and cortisol are a risk factor for reduced executive function (EF).

Investigators conducted a single-center, population-based case-control study with 100 early adolescents (aged 10 to 15 years [mean [SD] age, 13.3 [1.3] years]) with cCHD and 104 controlsto understand if cCHD influences physiological stress markers, EF, and resilience in early adolescents.

The team collected hair samples to evaluate physiological stress markers (cortisol and cortisone concentration), conducted a neuropsychological test to evaluate EF, and used a standardized self-report questionnaire to evaluate resiliency.

Upon adjusting scores for age, sex, and parental education, patients with cCHD had significantly higher stress compared with control patients, measured via cortisol and cortisone concentrations in the hair (β, 0.28 [95% CI, 0.12 to 0.43]; P < .001). Those with cCHD also demonstrated poor EF compared to controls (β, −0.36 [95% CI, −0.49 to −0.23]; P < .001).

Stress was also linked with EF and this negative association was stronger in patients with cCHD compared to controls (β, −0.65 [95% CI, −1.15 to −0.15]; P = .01). Despite previous studies which suggest that cCHD is linked to resiliency, the current results showed that cCHD does not increase patient resiliency compared with healthy children. Authors do note that reduced EF (associated with cCHD and stress) could decrease introspection and ability to determine self-resiliency.

The study did not some limitations. Firstly, it cannot determine causality. In addition, there were confounding variables that influence cortisol and cortisone concentrations in the hair. Further, there was no evaluation of perceived psychological stress, and the resiliency questionnaire was not fully comprehensive.

Authors discuss early-life interventions that may reduce neurodevelopment outcomes in patients with cCHD, such as promoting intimate parent–infant togetherness, kangaroo care, breastfeeding, music therapy, and ICU-based trauma-informed care, to name a few. It’s important to reduce stress in early life because stress can increase cortisol, which could be a biomarker for neurodevelopmental outcomes. More research is needed to evaluate this.

“Longitudinal studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopmental outcomes in patients with cCHD,” the authors concluded.


von Werdt L, Binz TM, O’Gorman RT, et al. Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease. JAMA Netw Open. 2024;7(2):e2355373. doi:10.1001/jamanetworkopen.2023.55373

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