Cardioventilatory Control in Preterm-born Children and the Risk of Obstructive Sleep Apnea

Rationale: The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in preterm-born children is unknown. Objectives: To characterize phenotypes of ventilatory control that are associated with the presence of OSA in preterm-born children during early childhood. Methods: Preterm-and term-born children without comorbid conditions were enrolled. They were categorized into an OSA group and a non-OSA group on the basis of polysomnography. Measurements and Main Results: Loop gain, controller gain, and plant gain, reflecting ventilatory instability, chemoreceptor sensitivity, and blood gas response to a change in ventilation, respectively, were estimated from spontaneous sighs identified during polysomnography. Cardiorespiratory coupling, a measure of brainstem maturation, was estimated by measuring the interval between inspiration and the preceding electrocardiogram R-wave. Cluster analysis was performed to develop phenotypes based on controller gain, plant gain, cardiorespiratory coupling, and gestational age. The study included 92 children, 63 of whom were born preterm (41% OSA) and 29 of whom were born at term (48% OSA). Three phenotypes of ventilatory control were derived with risks for OSA being 8%, 47%, and 77% in clusters 1, 2, and 3, respectively. There was a stepwise decrease in controller gain and an increase in plant gain from clusters 1 to 3. Children in cluster 1 had significantly higher cardiorespiratory coupling and gestational age than clusters 2 and 3. No difference in loop gain was found between clusters. Conclusions: The risk for OSA could be stratified according to controller gain, plant gain, cardiorespiratory coupling, and gestational age. These findings could guide personalized care for children at risk for OSA.