Ritchie Centre for Baby Health Research

Cardiovascular fetal & neonatal physiology

Sleep disordered breathing in children: implications for adult cardiovascular disease
Sleep disordered breathing (SDB) in children is represented by a continuum of symptoms ranging from mild to severe. Snoring is the mildest and most common form of SDB and occurs in up to 250,000 Australian children. The most severe form occurs when the airway closes intermittently during sleep and airflow into the lung ceases in what is known as obstructive sleep apnoea (OSA). It was once thought that only severe OSA was of clinical significance, but recent studies suggest that even mild SDB can adversely impact on daytime functioning and school performance. The key question we seek to answer is whether SDB in infants has long-term consequences for the child just as untreated SDB in adults has been shown to lead to hypertension and increased risk for cardiovascular disease and stroke.

We are currently investigating how SDB affects cardiovascular, behavioural and neuropsychological outcomes of preschool and primary school children. Our unique studies combine a full clinical description of SDB severity, continuous non-invasive measurement of blood pressure, spectral analysis of brain activity and complete behavioural and neurocognitive testing. Our preliminary data suggest that even mild SDB in primary school children increases blood pressure and heart rate as well elevated behavioural and neurocognitive problems. We plan to follow up our cohort of children to assess whether treatment of SDB reverses hypertension and behavioural and neurocognitive deficits. We will also investigate the cardiovascular effects of SDB in Down Syndrome children who are at much greater risk of SDB.

Bedside monitoring of cerebral oxygenation in infants with hypoxic-ischaemic cerebral injury
Hypoxic ischaemic encephalopathy (HIE) occurs in 2 to 3 cases per 1000 term births, with mortality rates of 10-60%, and at least 25% of survivors having neurodevelopmental sequelae. Based on experimental and clinical evidence that therapeutic hypothermia is beneficial to term newborns with HIE, tertiary neonatal units now offer whole body cooling as recommended therapy. Yet, there are significant unresolved issues in the application of cooling, including uncertainty relating to appropriate monitoring during cooling and re-warming, potential side effects, and long-term outcome.

To assess the effectiveness of cooling we have been using Near Infrared Spectroscopy (NIRS) to create bedside measures of cerebral haemodynamics and oxygenation in HIE infants that can be employed at the bedside soon after birth and during the period of cooling and rewarming. The tissue oxygenation index (TOI) allows us to continuously monitor autoregulation in the cerebral circulation by quantifying the coherence of arterial pressure and TOI in frequency-domain analysis. Our results to date show that cotside measurements of TOI in HIE infants allow us to monitor cerebral injury, the response to hypothermia and rewarming, and the effects of spontaneous cardiovascular changes and those resulting from drug treatment. A full assessment of the value of TOI monitoring awaits a study as to whether it has a beneficial impact on neurodevelopmental outcome.

Impact of dopamine on the cerebral oxygen metabolism in the immature brain
Acquired cerebral injury and subsequent neurodevelopmental disability is a serious problem for infants born prematurely. Although the proposed aetiologies are complex, many of them invoke abnormal regulation of cerebral blood flow (CBF). There is now substantial evidence that CBF in preterm infants varies directly with the level of mean arterial pressure (MAP), implying that hypotension would lead to cerebral ischaemia. Given the risks of hypotension, inotropic agents, mainly dopamine, are widely used for the maintaining MAP in preterm infants, in order to preserve organ perfusion, particularly CBF. Despite the widespread use of dopamine in preterm infants, there is currently no information available on the effects of dopamine on the interrelationships between CBF, cerebral tissue oxygen delivery and cerebral oxygen consumption in the immature brain.

We have already obtained data in preterm infants demonstrating that dopamine can promote cerebral blood flow-metabolism coupling which is a fundamental feature of the mature brain. It is possible that as a result of dopamine promoting the vascular tone, cerebral vessels in the immature brain may overcome “vasoparalysis” and recover their intrinsic ability to vasoconstrict and autoregulate. Experimental studies using animal models receiving dopamine after an induced hypotension would help to clarify the potential mechanisms and the time course of recovery of vessel reactivity and autoregulation. The clinical significance of such studies is that a dopamine-induced improvement of flow-metabolic coupling may confer neuroprotective effects in the immature brain at risk of hypoxic-ischaemic injury.