Early adolescents with complex congenital heart disease have higher stress markers

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Findings indicate that chronically high stress markers could have a role in the development of EF impairments in early adolescents with cCHD.

Early adolescents with complex congenital heart disease have higher stress markers | Image Credit: © MQ-Illustrations - © MQ-Illustrations - stock.adobe.com.

Early adolescents with complex congenital heart disease have higher stress markers | Image Credit: © MQ-Illustrations - © MQ-Illustrations - stock.adobe.com.

A study published in JAMA Network Open provided evidence that early adolescents with complex congenital heart disease (cCHD), who underwent infant open-heart surgery, had higher stress markers and lower executive functioning (EF), compared to healthy early adolescents.

To assess the association of cCHD in early adolescents with EF and resilience, the study authors investigated potential differences between adolescents aged 10 to 15 years with cCHD and healthy individuals in physiological stress markers by hair analysis, EF performance, and resilience.

The design was a single-center, population-based, case-control study conducted at the University Children’s Hospital Zurich, Switzerland. The case-control study was part of a prospective cohort study (Teen Heart Study) that investigated neurodevelopment outcomes and cerebral magnetic resonance imaging in early adolescents with cCHD. The study was conducted between April 2019 and September 2021.

Patients with cCHD who underwent cardiopulmonary bypass surgery (CPB) between 2004 to 2012 were included. Patients had to undergo CPB surgery before 1 year of ago, not be diagnosed with genetic or dysmorphic syndrome, and be between 10 and 15 years of age at the time of assessment to be eligible.

Of the 178 eligible patients, 100 early adolescents with cCHD participated in the study, with a 56% completion rate. A control group featured 104 healthy early adolescents aged 10 to 15 years, recruited with the following exclusion criteria:

  • Preterm birth (<36 weeks of gestation)
  • Diagnosed with a neurological or substantial developmental disorder

Individuals in the control group were recruited as friends of the participating patients via print and online advertisement.

“The analysis of the stress markers, cortisol and its metabolite cortisone, was conducted using 1 strand of hair collected from the posterior vertex region,” wrote the study authors. “A 3-centimeter hair segment was cut proximally to the scalp. At a mean growth rate of 1-centimeter per month, this represents the cumulative cortisol and cortisone concentration of the past 3 months.”

An extensive standardized neuropsychological test battery was used to investigate EFs, while resilience was assessed with the Resilience Scale 13 (RS-13), that measures self-reported personality traits of acceptance of self and life and personal competences.

“This questionnaire has good internal consistency and acceptable test-retest reliability, can be used in adolescents and adults, and has been applied in various patient samples,” the investigators wrote. Participants rate the accuracy of 13 statements on a 7-point scale, with higher scores indicating higher resilience. The sum score was calculated and used for statistical analysis.

Participants had a mean age 13.3 (1.3) years and 53.9% were male. Patients had significantly higher sums of hair cortisol and cortisone concentrations (β, 0.28 [95% CI, 0.12 to 0.43]; P < .001) and lower EF scores (β, −0.36 [95% CI, −0.49 to −0.23]; P < .001) when adjusted for age, sex, and parental education compared to the individuals in the control group.

No group difference was observed in self-reported resilience (β, −0.04 [95% CI, −0.23 to 0.12]; P = .63), though a “significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (β, −0.65 [95% CI, −1.15 to −0.15]; P = .01),” wrote the study investigators. The authors added that contrast effects were not significant in patients (β, −0.21 [95% CI, −0.43 to −0.00]; P = .06) or control individuals (β, 0.09 [95% CI, −0.11 to 0.30]; P = .38).

Group interactions revealed an association between higher stress markers and lower EF performance in the cCHD group. These findings indicate that chronically high stress markers could have a role in the development of EF impairments in the early adolescents with cCHD.

“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,” stated the investigators in conclusion.

Reference:

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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