Sudden Infant Death Syndrome (SIDS) and Sleep Apnoea Research

Group Leader
A/Prof Karen Waters,
Conjoint Associate Professor, CHW and University of Sydney
Phone: 02 9845 3437
Fax: 9845 3396
Email: karenw2@chw.edu.au

Current research program

There are 2 streams, Clinical and Basic Science:

Clinical: The main focus of this work is to evaluate current treatments for children with obstructive sleep apnoea. One project is focusing on refining the treatment of mild sleep apnoea, which is the most common diagnosis.

A major, multicentre project is also being established to find out whether treatment of sleep apnoea improves the learning and behaviour problems seen in these children.

Basic Science: Our basic science studies are primarily evaluating the brain abnormalities that are found in infants who died from SIDS (sudden infant death syndrome). We also work with piglets so that we can expose them to models of the risk factors that are associated with SIDS. This helps us to determine the processes that cause the brain abnormalities being found. We are also developing proteomics methods for future studies so that we can examine the profile of several systems simultaneously and/or to identify new proteins that may be relevant to the disease processes associated with SIDS and sleep apnoea.

Major achievements in last 10 years

Over the past 10 years, this group completed a major series of projects regarding the occurrence of metabolic dysfunction in paediatric obstructive sleep apnoea. The work was funded by NH&MRC and by the NIH and Dr. Waters also held an NH&MRC Practitioner Fellowship during that period. We were able to examine a number of aspects of both disorders to clarify how obesity, sleep apnoea and insulin resistance interact in children.

Our studies in the brain tissue of SIDS infants and in piglets have shown a number of similarities and, by using the piglet model, we have been able to show that even exposure that occurs only in the post-natal period (to noxious stimuli that create known risk for SIDS) can produce similar brain abnormalities to those seen in SIDS infants. Those results support the hypothesis that an infants’ vulnerability to SIDS need not be present before birth to still predispose the child to sudden death.

Five key publications with comments on their significance.

Machaalani R, Waters KA (2008) Neuronal cell death in the Sudden Infant Death Syndrome brainstem and associations with risk factors. Brain, 131: 218-228.
This paper was the culmination of several years of work on the dataset of infant tissue as we had to examine more than one apoptotic marker. The study follows on from our previous publication, first published in 1999, reporting the initial finding of neuronal apoptosis in a group of infants who had died from SIDS, in Canada. (Waters KA, Meehan B, Huang JQ, Gravel RA, Michaud J, Côté A. Neuronal apoptosis in sudden infant death syndrome. Pediatr Res. 1999 Feb;45(2):166-72.)

Waters KA, Tinworth KD. Effect of stimulus cycle time on acute respiratory responses to intermittent hypercapnic hypoxia in unsedated piglets. J Appl Physiol. 2003 Jun;94(6):2465-74.
This paper was very important to the understanding of the number of processes that are disrupted in response to an intermittent hypoxic stimulus. In contrast to many studies, we used high CO2 as well as low oxygen exposures. From these results, we established a model of intermittent hypercapnic hypoxia (IHH) that creates most disruption to physiological processes. That model has been used in our subsequent work on neuronal abnormalities.

Tam CS, Wong M, Tam K, Aouad L, Waters KA (2007) The effect of Acute Intermittent Hypercapnic Hypoxia treatment on IL-6, TNF-α, and CRP levels in piglets. Sleep. 30(6):723-7. IF 5.126
This paper is one of the manuscripts arising from the studies of metabolic abnormalities, but it is important because it shows the benefits of using an animal model to set-up structured studies to evaluate profiles that may also occur in clinical diseases. The abnormalities seen in the piglets help to guide studies about the origins of metabolic disorders in association with the blood gas abnormalities that occur in obstructive sleep apnoea in children.

MacLean JE, Fitzsimons D, Hayward P, Waters KA, Fitzgerald DA. The identification of children with cleft palate and sleep disordered breathing using a referral system. Pediatr Pulmonol. 2008 Mar;43(3):245-50.
This paper marks the start of a series of research studies by Dr. MacLean. She is investigating the prevalence and impact of obstructive sleep apnoea in infants with a diagnosis of cleft palate. A series of follow-up studies will be undertaken that will help to establish how our clinical practice should be structured for these children to ensure that they are appropriately screened and treated for airway obstruction.

Waters KA, McBrien F, Stewart P, Hinder M, Wharton S. Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children. J Appl Physiol. 2002 May;92(5):1987-94.
This paper also represents the start of another series of studies. We are currently shifting to a program to evaluate the peri-operative issues confronted by children with obstructive sleep apnoea. Included amongst those are assessments of whether any pre-operative interventions can improve childrens’ responses to surgery as well as determining (by follow-up) how much improvement can be expected from their baseline.

Research Staff

Post-doctoral fellows:

• Dr. Rita Machaalani, BSc(Hon), PhD
• Dr. Bronwyn Relf, BSc(Hon), PhD

Research Assistant

• Ms Chenda Kol, BSc(Hon)MSc

Administrative Assistant

• Ms Kate Blakeney

PhD students

• Ms Samantha Tang
• Ms Carla Evans
• Ms Rebecca Hensley

Honour Students

• Ms Sara Tan
• Ms Warde Elias
• Ms Leshni Pillay

Research support (2005-2008)

• NHMRC/ARC : 2 NHMRC, $365,816.00
• Other Government competitive funds : 1 x NIH $USD210,000
• Government non-competitive fund: Nil
• Funds from industry: Nil
• Other competitive fund: University of Sydney, Bridge funding for Practitioner Fellowship
• Other non-competitive fund: ASTN funding for establishment of Multi-centre research study $25,000.00

Opportunities for Students

Postgraduate Research available at the University of Sydney.