Development of cardiovascular control during sleep in infants after preterm birth

Preterm birth is associated in both the short and long-term with considerable cardiovascular morbidity. Preterm infants exhibit depressed cardiac baroreflex sensitivity during sleep at term-equivalent age, and epidemiological studies have identified preterm birth as one of the major risk factors for Sudden Infant Death Syndrome (SIDS). A common factor identified in many future SIDS infants is depressed autonomic nervous system (ANS) control of heart rate (HR) and blood pressure (BP). Thus, it has been proposed that a failure to mount an adequate cerebellar-mediated cardiorespiratory response to overcome profound hypotension may play a role in the fatal event of SIDS. Immature or depressed ANS control may therefore underpin the increased risk for SIDS in preterm infants. To date, the majority of studies on preterm infant cardiovascular control have been based on invasive or intermittent BP measurements, and there is a paucity of data relating to BP and its control, particularly during sleep which is known to have a profound effect on cardiovascular control in the first months of term-equivalent age. Despite intensive research, the effects of sleep state, age, and preterm birth on cardiovascular control are poorly understood during this period of increased SIDS risk. Using a new, non-invasive technique to measure continuous BP, we aimed to provide novel information on the effects of sleep state, age and preterm birth on cardiovascular control in infants after reaching term-equivalent age. Preterm and term infants were studied using daytime polysomnography at 2-4 weeks, 2-3 months and 5-6 months term-corrected age (CA), encompassing the period when SIDS risk is greatest SIDS. We found that both sleep state and age have marked effects on HR, BP and cardiovascular control in preterm infants studied across the first 6 months CA. We found that HR and BP were higher and more variable in active sleep (AS) compared to quiet sleep (QS), and that responses to head-up tilting, as well as baroreflex sensitivity were also altered by sleep state. Similar to previous findings in healthy term infants, we also identified that BP averaged lower at 2-3 months CA compared with both 2-4 weeks and 5-6 months CA. BP responses to head-up tilting (HUT), baroreflex sensitivity and cardiovascular variability during QS also improved with maturation in preterm infants. We also compared preterm infants with age-matched term infants to assess the effect of preterm birth on cardiovascular control during sleep. We found that preterm birth has a profound effect on systemic vascular control, with preterm infants exhibiting lower BP, delayed BP recovery after HUT, reduced baroreflex sensitivity and altered BP variability. Our findings suggest that ANS control during sleep is impaired in preterm infants; a deficit which persists across the first 6 months CA. We speculate that impaired ANS control may place an already vulnerable preterm infant at an increased risk for SIDS. In summary, this thesis provides the first longitudinal studies to assess the effects of sleep state, age and preterm birth on cardiovascular control. We found that both sleep state and age exhibit marked effects on systemic cardiovascular control in preterm infants across the first 6 months CA. Notably, we identified a profound and persisting effect of preterm birth on ANS control during sleep across the first 6 months CA. Preterm infants exhibited impaired or altered systemic vascular control and altered BP variability during sleep; a deficit which may contribute to their increased vulnerability for SIDS and cardiovascular morbidity later in life.