Cerebral oxygenation during sleep in preterm infants

Abstract

The Sudden Infant Death Syndrome (SIDS) remains the leading cause of death in the post-neonatal period in developed countries (Hauck and Tanabe, 2008). Despite much research, the exact mechanisms underlying SIDS remain unclear, but are thought to involve immature cardiovascular control leading to an uncompensated hypotensive episode, in conjunction with a failure to arouse from sleep (Harper, 2000). The vast majority of SIDS deaths occur within the first six months of life with a distinct peak occurring between 2-3 months of age and the prone sleeping position is well known to be a major risk factor for SIDS (Trachtenberg et al., 2012). This is particularly so amongst infants born preterm who are known to be at significantly increased risk for SIDS (Blair et al., 2006a). Preterm birth is common and increasing in incidence (Blencowe et al., 2012). Prematurity is associated with multiple consequences including altered cardiovascular control, which has been suggested to underlie their increased risk for SIDS (Trachtenberg et al., 2012), as well as cardiovascular disease later in life (Parkinson et al., 2013). Immaturity of cardiovascular control has been illustrated in studies assessing autonomic control of the cardiovascular system. Preterm infants have been shown to have higher heart rates (HR) and reduced heart rate variability (HRV) (Eiselt et al., 1993, Patural et al., 2004) compared to term infants at term-equivalent age. Furthermore, beyond term-equivalent preterm infants display altered cardiovascular control with impaired maturation of HRV (Yiallourou et al., 2013) and baroreflex sensitivity (Witcombe et al., 2012). However, preterm infants have not previously been studied in the prone sleep position during the period of peak risk for SIDS. In healthy term infants, prone sleeping has been associated with reduced BP (Yiallourou et al., 2008a) and altered cardiovascular control (Yiallourou et al., 2008b, Yiallourou et al., 2011). More recently, prone sleeping has also been shown to result in reductions in cerebral oxygenation (Wong et al., 2011) and altered cerebrovascular control (Wong et al., 2013) in term infants. Our group have suggested that reduced cerebral oxygenation in the prone position, resulting in brainstem hypoxia, may contribute to altered brainstem function including impaired autonomic cardiovascular control and reduced arousal. The aims of this thesis were to assess cerebral oxygenation, cerebrovascular and cardiovascular control during sleep in both the prone and supine positions in preterm infants across the first six months post-term. The studies in Chapter 3 have shown that cerebral oxygenation is reduced in the prone sleeping position in preterm infants until at least 5-6 months post-term age. Furthermore, cerebral oxygenation is reduced in preterm compared to term infants, most prominently at 2-3 months post-term in the prone position. This reduction coincided with a concurrent reduction in BP and HR in preterm infants in the prone position during this period. The studies in Chapter 4 have shown that cerebrovascular control is altered by sleep position in preterm infants. Furthermore, whilst overall cerebrovascular control was similar between term and preterm infants, preterm infants displayed greater variability suggesting immaturity of cerebrovascular control persists beyond term-equivalent age. In Chapter 5 and 6 we have shown that maturation of both baroreflex function and HRV is affected by preterm birth with delayed maturation seen particularly amongst infants born at earlier gestational ages. The findings of this thesis may have significant implications for SIDS. Infants born preterm have significantly reduced cerebral oxygenation and immature cerebrovascular control, particularly in the prone sleep position, and this may contribute to their increased risk for SIDS. Furthermore, altered maturation of cardiovascular control following preterm birth, particularly in infants born at earlier gestational ages, may predispose these infants to cardiovascular disease later in life. Awards: Winner of the School of Clinical Sciences Head of School’s PhD Excellence in 2014.