The following is a summary of “Ventilatory and Orthostatic Challenges Reveal Biomarkers for Neurocognition in Children and Young Adults With Congenital Central Hypoventilation Syndrome,” published in the June 2023 issue of the Chest by Slattery et al.
Cognitive deficits are a risk for children and young adults with congenital central hypoventilation syndrome (CCHS). During ventilatory and orthostatic challenges, they exhibit autonomic dysfunction and chemoreceptor insensitivity, but the relationships between these features are unknown. Can a biomarker associated with neurocognitive outcomes in CCHS be identified using physiologic responses to ventilatory and orthostatic challenges? This retrospective study included 25 children and adolescents with CCHS evaluated during hospitalization. Examining the associations between physiologic measurements during hypercarbia and hypoxic ventilatory challenges, hypoxic ventilatory challenges, orthostatic challenges, and neurocognitive outcomes (as measured by Wechsler intelligence indices).
Significant Pearson correlations determined the inclusion of independent variables. Multivariate linear regressions evaluated relationships between measured physiologic responses to challenges and neurocognitive scores. During challenges, significant relationships were found between aspects of fluid intelligence and measures of oxygen saturation (SpO2) and heart rate (HR). Specifically, perceptual reasoning was associated with HR during orthostasis (adjusted regression [β] coefficient, –0.68; 95% CI, 1.24 to –0.12; P =.02). During the hypoxic ventilatory challenge, working memory was associated with HR change (β= -1.33; 95% CI = -2.61 to -0.05; P =.042).
Processing speed was related to HR (β, –1.19; 95% CI, –1.93 to –0.46; P = .003) during orthostasis, to baseline SpO2 (hypercarbia and hypoxic β, 8.57 [95% CI, 1.63-15.51]; hypoxic β, 8.37 [95% CI, 3.65-13.11]; P = .002 for both) during the ventilatory challenges, and to intrachallenge SpO2 (β, 5.89; 95% CI, 0.71-11.07; P = .028) during the hypoxic ventilatory challenge. SpO2 and HR—or change in HR—at rest and in response to hypoxia and orthostasis are associated with cognitive outcomes in known risk domains and remarkably fluid reasoning in children and young adults with CCHS. These results can guide future research on the utility of these biomarkers in determining the effect of daily physical stressors on neurodevelopment in this high-risk population.