Prevention & Cure

Summary

Current Projects

  • Investigating the link between congenital CMV and cerebral palsy – the stored blood spot study
  • Genetic study for term infants at low risk of CP
  • Preventing adverse outcomes of neonatal encephalopathy with Erythropoietin – the PAEAN study (NHMRC)
  • Working to improve survival and health for babies born very preterm (WISH and WISH Follow Up)
  • Magnesium sulphate at 30 to 34 weeks’ gestational age: neuroprotection trial – the MAGENTA study (NHMRC)
  • Use of the General Movements assessment to predict outcomes at one year of age in the neonatal surgical population
  • Neuroprotective role of sulphate among preterm babies – the SuPreme study (NHMRC)
  • Preventing cerebral palsy: The impact of therapeutic hypothermia in neonatal encephalopathy in Australia
  • Investigating the contribution of birth defects to the aetiology of CP
  • An exploration of cerebral palsy aetiology: assisted reproductive technologies and congenital anomalies
  • A study of the impact of treating electrographic seizures in newborn infants with encephalopathy (NHMRC)

Completed projects

  • Clinical and neuroimaging findings in a retrospective study of children with cerebral palsy associated with congenital cytomegalovirus infection
  • Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population-based study
  • A genomic basis for cerebral palsy – studies on a large Australian cohort
  • Cerebral palsy in children born at term: analysis of the WA case-control study
  • Chorioamnionitis and cerebral palsy: A meta-analysis

Current Projects

Investigating the link between congenital CMV and cerebral palsy – the stored blood spot study

Cerebral Palsy Alliance Investigators: Hayley Smithers-Sheedy, Nadia Badawi, Sarah McIntyre
Co-Investigators: Cheryl Jones (University of Sydney), Alison Kesson (University of Sydney), Camille Raynes-Greenow (University of Sydney)

Cytomegalovirus (CMV) is a common virus that circulates virtually unnoticed in our community. CMV can be transmitted from mother to the unborn child, and is a potentially preventable causal pathway to cerebral palsy (CP). The proportion of CP due to CMV remains unclear in Australia as screening for CMV is not routinely performed in newborn infants and some infants show no signs of infection when they are born. All children in Australia routinely have a ‘heel prick’ test shortly after birth to test for inherited conditions. The blood is collected on filter paper (the ‘newborn screening card’) and then stored. The aims of this study are to test the stored newborn screening cards of children with cerebral palsy for the virus, CMV, and to link this information with data from Cerebral Palsy Alliance to describe the clinical features of children with CP attributed to CMV. This study is recruiting: eligible participants are children with CP born in NSW from 1996-2012.


Genetic study for term infants at low risk of CP

Cerebral Palsy Alliance Investigator: Sarah McIntyre
Co-Investigator: Michael Kruer (Sanford Children’s Health Research Center, USA)

Up to one third of children with CP have no clear risk factors for their condition, and the cause of their CP remains unknown. Recent findings suggest that for some of these children, there is in fact a genetic basis for their CP, but the study of genetic causes of CP is in its infancy. This study seeks to address this current limitation in our understanding of the neurobiology of CP. By studying DNA samples from children with CP of uncertain cause and their parents, using next-generation sequencing methods, we will identify mutations in novel genes that lead to CP. This will allow us to gain new insights into crucial brain pathways that, when disturbed, lead to CP, and improve diagnosis in the near future while implicating important biological processes in CP for the first time.


Preventing adverse outcomes of neonatal encephalopathy with Erythropoietin – the PAEAN study

Cerebral Palsy Alliance Investigator: Sarah McIntyre, Nadia Badawi, Iona Novak

Funding: NHMRC Project Grant (ref 1064294)
Chief Investigators: Helen Liley (Mater Hospital), Nadia Badawi, Susan Jacobs (University of Melbourne), Rachel O’Connell (University of Sydney), Malcolm Battin (Auckland City Hospital), Rod Hunt (Murdoch Children’s Research Institute), Iona Novak, Lisa Askie (University of Sydney)

A lack of oxygen (hypoxia) or low blood supply (ischaemia) before or during birth can destroy cells in a newborn baby’s brain. The damage caused by the lack of oxygen continues for some time afterwards. One way to try to reduce this damage is to induce hypothermia: cooling the baby or just the baby’s head for hours to days. Erythropoietin (Epo) given in the first week after birth shows promise as a treatment that may also help. This study is to find out whether Epo plus induced hypothermia (cooling) of near term newborn babies, who have suffered from low blood or oxygen supply to the brain at birth, reduces death and disability in survivors at two years of age.


Working to improve survival and health for babies born very preterm (WISH and WISH Follow Up)

Cerebral Palsy Alliance Investigator: Sarah McIntyre
Co-Investigators: Caroline Crowther (University of Adelaide), Phillipa Middleton (University of Adelaide), Vicky Flenady (Mater Research Institute), Jonathon Morris (University of Sydney), Michael Beckman (Mater Health Brisbane), Katie Groom (Auckland City Hospital)

This project aims to nationally monitor and improve uptake of the use of antenatal magnesium sulphate as a neuroprotective therapy immediately prior to imminent (planned birth or definitely expected within 24 hours) early preterm (<30 weeks gestation) birth to reduce the risk of the baby dying or having cerebral palsy. This project will use CP Register data to evaluate the impact of antenatal treatments.


Magnesium sulphate at 30 to 34 weeks’ gestational age: neuroprotection trial – the MAGENTA study

Cerebral Palsy Alliance Investigator: Sarah McIntyre

Funding: NHMRC Project Grant (ref 1022968)
Chief Investigators: Caroline Crowther (University of Adelaide), Phillipa Middleton (University of Adelaide), Dominic Wilkinson (Oxford University), Ross Haslam (Women’s and Children’s Hospital, Adelaide)

Magnesium sulphate is currently recommended for neuroprotection of preterm infants for women at risk of preterm birth at less than 30 weeks’ gestation, based on high quality evidence of benefit. However there remains uncertainty as to whether these benefits apply at higher gestational ages. The aim of this randomised controlled trial is to assess whether giving magnesium sulphate compared with placebo to women immediately prior to preterm birth between 30 and 34 weeks of gestation reduces the risk of death or cerebral palsy in their children at two years’ corrected age. For this study, the collaborating centres are in Australia and New Zealand.


Use of the General Movements assessment to predict outcomes at one year of age in the neonatal surgical population

Cerebral Palsy Alliance Investigators: Karen Walker, Nadia Badawi, Iona Novak
Co-Investigator: Cathryn Crowle (University of Sydney)

The historical wait and see approach to the diagnosis of neurodevelopmental delay is no longer the only option. Neonatal intensive care units (NICUs) are working towards the early diagnosis of neurodevelopmental disability in high risk babies, such as those who undergo major surgery. Although early identification is challenging, it is essential in order to provide timely intervention to promote optimum development. The aim of this study is to ascertain whether the General Movements (GMs) assessment can identify those at risk and predict outcomes in the neonatal surgical population. GMs assessment has not been previously reported in a group of infants who have undergone major surgery. Within the surgical NICU ‘poor repertoire’ movements are common. This assessment has changed clinical practice by earlier referral to specialised services for those at risk. Further research will determine whether GMs will predict outcomes at twelve months of age.

Publication:
Crowle C, Badawi N, Walker K, Novak I. General Movements Assessment of infants in the neonatal intensive care unit following surgery. Journal of Paediatrics and Child Health. 2015. DOI: 10.1111/jpc.12886


Neuroprotective role of sulphate among preterm babies – the SuPreme study

Cerebral Palsy Alliance Investigators: Nadia Badawi, Cathy Morgan, Sarah McIntyre

NHMRC Project Grant (ref 1081911)
Chief Investigators: Paul Dawson (Mater Research Institute), Nadia Badawi (Cerebral Palsy Alliance), Roslyn Boyd (University of Queensland), Vicky Flenady (Mater Research Institute), Elizabeth Hurrion (Mater Children’s Hospital), Francis Bowling (Mater Children’s Hospital), Pieter Koorts (Royal Brisbane & Women’s Hospital, Sailesh Kumar (Mater Mothers’ Hospital)

Each year, 8% of Australian infants are born preterm which places them at increased risk of life-long poor health outcomes, including cerebral palsy and cognitive dysfunction. Our research into the neuroprotective role of sulphate among preterm babies will address this important health issue. The overarching aims of this study are to determine the role of neonatal sulphate status in adverse neurodevelopmental outcomes among preterm-born children and to better understand sulphate biochemistry in order to develop a simple efficacious neuroprotection therapy for preterm infants.


Preventing cerebral palsy: the impact of therapeutic hypothermia in neonatal encephalopathy in Australia

Cerebral Palsy Alliance Investigators: Sarah McIntyre, Nadia Badawi
Co-Investigators: Kei Lui (University of New South Wales), Sheilander Mehta (PhD Candidate, University of New South Wales)

This project series will evaluate the impact of therapeutic hypothermia in reducing cerebral palsy as a result of peripartum hypoxic ischemic insults. It is also envisaged that findings could identify gaps and assist in the dissemination of knowledge and implementation of the treatment. Long term outcome and economic implications are being evaluated.


Investigating the contribution of birth defects to the aetiology of CP

Cerebral Palsy Alliance Investigators: Sarah McIntyre, Nadia Badawi, Shona Goldsmith
Co-Investigators: Eve Blair (University of Western Australia), Karin B. Nelson (Children’s National Medical Centre, Washington DC), Carol Bower (University of Western Australia)

This study will conduct new data linkages between CP Registers and Birth Defect Registers across a number of states in Australia. These linkages will quantify the contribution to CP; specific pathways that include birth defects and growth restriction will be determined with the ultimate aim of identifying preventive opportunities.


An exploration of cerebral palsy aetiology: assisted reproductive technologies and congenital anomalies

Cerebral Palsy Alliance Investigators: Shona Goldsmith, Sarah McIntyre, Nadia Badawi
Co-Investigators: Michelle Hansen (Telethon Institute for Child Health Research, WA)

The aim of this research program is to further understand the significance of two known risk factors in causal pathways to cerebral palsy (assisted reproductive technology and congenital anomalies). Specifically, it aims to:
Study 1: Investigate the relationship between assisted reproductive technology and cerebral palsy in a West Australian-born population;
Study 2: Quantify the effect of assisted reproductive technology on the risk of cerebral palsy (systematic review and meta-analysis);
Study 3: Determine the proportion of congenital anomalies in children with CP (systematic review and meta-analysis);
Study 4: Explore the relationship between congenital anomalies and CP in a national, Australian-born population.


A study of the impact of treating electrographic seizures in newborn infants with encephalopathy

Cerebral Palsy Alliance Investigators: Nadia Badawi, Karen Walker

NHMRC Project Grant (ref 1006053)
Chief Investigators: Rod Hunt (Murdoch Children’s Research Institute), Ian Wright, Karen Simmer (University of Western Australia), Terrie Inder (Brigham & Women’s Hospital, USA), David Osborn (RPA Hospital), Nadia Badawi, Paul Colditz (University of Queensland), Jeanie Cheong (MCRI), Helen Liley (University of Queensland)

Seizures in the newborn infant are common and may be harmful to the developing brain. They are not always recognised. This study investigates whether or not treating all seizures detected using a bedside brain activity monitor improves developmental outcome, compared to just treating seizures that doctors recognise.


Completed Projects

Clinical and neuroimaging findings in a retrospective study of children with cerebral palsy associated with congenital cytomegalovirus infection

Primary investigators: Hayley Smithers-Sheedy (Cerebral Palsy Alliance), Camille Raynes-Greenow (University of Sydney), Nadia Badawi (Cerebral Palsy Alliance), Sue Reid (Murdoch Children’s Research Institute), Elaine Meehan (Murdoch Children’s Research Institute), Catherine Gibson (University of Adelaide), Russell Dale (University of Sydney), Cheryl Jones (University of Sydney)

Congenital cytomegalovirus (cCMV) is a contributing cause of neurodevelopmental disabilities including cerebral palsy.

This study described the clinico-radiological profile of children with cerebral palsy and associated cCMV infection. Data was available for children: with cerebral palsy and laboratory confirmed cCMV as reported to the Australian Cerebral Palsy Register; who were born in South Australia and Victoria from 1993-2006; with evidence of confirmed/probable cCMV infection; and with magnetic resonance imaging and/or computerized tomography reports. Clinical details and neuroimaging findings were reported.

Smithers-Sheedy, H., C. Raynes-Greenow, N. Badawi, S. Reid, E. Meehan, C. Gibson, R. C. Dale and C. Jones (2014). “Clinical and neuroimaging findings in children with cerebral palsy associated with congenital cytomegalovirus. Dev Med Child Neurol 56(S5): 69-70.


Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population-based study

Primary investigators: Hayley Smithers-Sheedy (Cerebral Palsy Alliance), Camille Raynes-Greenow (University of Sydney), Nadia Badawi(Cerebral Palsy Alliance), Sarah McIntyre (Cerebral Palsy Alliance) Cheryl Jones (University of Sydney), The Australian Cerebral Palsy Register Group

Congenital cytomegalovirus (cCMV) infection can result in poor outcomes including cerebral palsy. The aim of this study was to describe the incidence and comorbidities of cerebral palsy reported to the Australian Cerebral Palsy Register (ACPR) as attributed to cCMV infection. This was a retrospective population-based study: cases were drawn from Australian state cerebral palsy registers with population level ascertainment, 1993 to 2003 (n=2265).

Clinical data were extracted and cases with cCMV reported as a known cause were compared with cases where cCMV was not reported.

Smithers-Sheedy H, Raynes-Greenow C, Badawi N, McIntyre S, Jones CA. Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population-based study. Dev Med Child Neurol. 2014. Epub 2014/04/23


A genomic basis for cerebral palsy – studies on a large Australian cohort

Primary investigators: Alastair MacLennan (University of Adelaide), Catherine Gibson (University of Adelaide), Paul Goldwater (Children’s, Youth and Women’s Health Service, Adelaide), Michael O’Callahan (University of Adelaide)

Associate investigators: Gustaaf Dekker (University of Adelaide), Eric Haan (Children’s, Youth and Women’s Health Service, Adelaide), Annabelle Chan (Department of Health, SA), Michael deLacy (Cerebral Palsy League of Queensland), Sarah McIntyre (Cerebral Palsy Alliance), Peter Flett (Calvary Rehabilitation Services)

This national cohort study investigated the role of gene mutations in altering the fetal inflammatory response and the risk of abnormal clotting in the causation of cerebral palsy. This was the largest study of its kind in the world.

O’Callaghan, M. E., A. H. MacLennan, et al. (2011). “The Australian cerebral palsy research study–protocol for a national collaborative study investigating genomic and clinical associations with cerebral palsy.” J Paediatr Child Health 47(3): 99-110.

O’Callaghan, M. E., A. H. MacLennan, et al. (2011). “Epidemiologic associations with cerebral palsy.” Obstet Gynecol 118(3): 576-582.

O’Callaghan, M. E., A. H. Maclennan, et al. (2013). “Genetic and clinical contributions to cerebral palsy: A multi-variable analysis.” J Paediatr Child Health 49(7): 575-581.


Cerebral palsy in children born at term: analysis of the WA case-control study

Primary investigators: Sarah McIntyre (Cerebral Palsy Alliance), Nadia Badawi (Cerebral Palsy Alliance), Eve Blair (University of Western Australia), John Keogh (Sydney Adventist Hospital), Karin B. Nelson (Children’s National Medical Centre, Washington DC)

This study sought to understand more about causal pathways to cerebral palsy, in particular for infants born at term (37+ weeks gestation). Infants who are born at term account for 60-65% of all cerebral palsy, yet because relative risk for cerebral palsy is much greater for those born early, research has focused on those born preterm.

This is the largest full population case-control study of term infants and includes all singletons with cerebral palsy born at term 1980-1995 in Western Australia and controls individually matched for gestation, plurality and birth year.

Preconceptional, antenatal, intrapartum, and neonatal information was collected and analysed. This research focussed on the most under-researched group, those born at term who are not considered to be sick in the neonatal period.

McIntyre S, Taitz D, Keogh J, Goldsmith S, Badawi N, Blair E. A systematic review of risk factors for cerebral palsy in children born at term in developed countries. Dev Med Child Neurol 2013;55:499-508.

McIntyre, S., Badawi, N., Brown, C. & Blair, E. (2011). Population case control study of cerebral palsy: neonatal predictors in low risk term singletons. Pediatrics, 127, 3:e667-673.

McIntyre, S., E. Blair, N. Badawi, J. Keogh and K. B. Nelson (2013). “Antecedents of cerebral palsy and perinatal death in term and late preterm singletons.” Obstet Gynecol 122(4): 869-877.


Chorioamnionitis and cerebral palsy: a meta-analysis

Primary investigators: Jobe Shatrov (University of Notre Dame Australia), Samuel Birch (University of Notre Dame Australia), Lawrence Lam (University of Sydney), Julie Quinlivan (Ramsay Health Care), Sarah McIntyre (Cerebral Palsy Alliance), George Mendz (University of Notre Dame Australia)

This study examined the relationships between clinical or histological chorioamnionitis and cerebral palsy using a meta-analysis approach following a systematic review of the literature. The significant association of clinical or histological chorioamnionitis with cerebral palsy suggested that clinical strategies to prevent or reduce chorioamnionitis would lead to a reduction in cerebral palsy.
The culture techniques currently used to diagnose the presence of pathogenic microorganisms during pregnancy need to improve, both in their methodology and in the length of time they require.

Shatrov, J., Birch, S., Lam, L., Quinlivan, J., McIntyre, S., Mendz, G. (2010). Chorioamnionitis and cerebral palsy: A meta-analysis. Obstetrics & Gynecology, 116(2 Pt 1), 387-392.