Ventilatory control instability as a predictor of persistent periodic breathing in preterm infants

Background: Periodic breathing (PB) is common in preterm infants. We aimed to characterize the contribution of ventilatory control instability to the presence and persistence of PB longitudinally. Methods: Infants born between 28 and 32 weeks of gestation were studied using daytime polysomnography at: 32–36 weeks postmenstrual age (PMA) (N = 32), 36–40 weeks PMA (N = 20), 3 months corrected age (CA) (N = 18) and 6 months CA (N = 19). Loop gain, a measure of sensitivity of the ventilatory control system, was estimated by fitting a mathematical model to ventilatory patterns associated with spontaneous sighs. Results: The time spent in PB decreased from 32–36 weeks PMA to 6 months CA (P = 0.005). Across all studies, studies with PB (N = 62) were associated with higher loop gain compared to those without PB (N = 23) (estimated marginal mean ± SEM: 0.445 ± 0.01 vs 0.388 ± 0.02; P = 0.020). A threshold of loop gain >0.415 (measured at 32–36 weeks PMA) provided a sensitivity of 86% and a specificity of 75% to detect the presence of PB at 6 months CA. Conclusions: The course of PB in preterm infants is related to changes in loop gain. Higher loop gain at 32–36 weeks PMA was associated with a greater risk of persistent PB at 6 months CA. Impact: The developmental trajectory of periodic breathing and its relationship to ventilatory control instability is currently unclear.Unstable ventilatory control is a determinant of periodic breathing in preterm infants up to 6 months corrected age.Infants who display greater ventilatory control instability at 32–36 weeks postmenstrual age may be at increased risk of persistent periodic breathing at 6 months corrected age.Assessment of ventilatory control stability may assist in the early identification of infants at risk of persistent periodic breathing and its potential adverse effects.