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The Robinson Research Institute's driving focus is giving and sustaining life for existing and future generations - that is creating life and making sure it's as healthy as possible throughout by finding cures and treatments for a range of health issues and illnesses.
Our research covers the whole life spectrum from:
- Conception and Fertility, with a focus on helping people realise their hopes of starting a family
- Healthy Start to Life, where the focus is on healthy pregnancies and infants' early years and;
- Regenerative medicine, where we're looking at the use of stem cells to cure a number of illnesses and disabilities including stroke and cystic fibrosis.
One of our greatest strengths is the way we link clinicians and our researchers, which means improved sharing of ideas and outcomes, meaning faster and better results for the community and for future generations.
The Robinson Institute is driven by the belief that our work has major life impacts with medical research holding the key to improving the health of future generations.
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Item Metadata only A 'no-fault' cerebral palsy pension scheme would benefit all Australians(Blackwell Publishing Asia, 2011) MacLennan, A.The Australian Federal Productivity Commission is proposing two new schemes to better support those with major disability. The main National Disability Insurance Scheme (NDIS) will provide long-term care and support for the disabled. A smaller scheme, the National Injury Insurance Scheme (NIIS), will provide ‘no-fault ‘support for those following an accident or ‘medical injury’. It is proposed that cerebral palsy (CP) is part of the NIIS. While this brings quicker and more equitable benefits to CP families, the scheme labels CP as a ‘medical accident’ and infers preventability. Obstetricians will fund much of the system. Despite being labelled a ‘no-fault’ system, maternity staff can still be litigated for extensive ‘head of damages’, eg loss of earning capacity. An additional option is for federal/state legislation to introduce a true ‘no-fault’ lifetime pension specifically for all children on CP registers. This pension would be graded by degree of disability and dependent on waiving civil litigation. Savings in medico-legal costs and potentially a 7% reduction in caesarean delivery would cover the estimated annual cost of $50 000 per annum indexed life pension for severe CP cases and the total annual cost of AUD $93 million for Australia. This pension and the NDIS would help cover the needs of children with CP without recourse to prolonged litigation and without detriment to the maternity services of Australia, caused by defensive obstetrics and maternity hospital closure because of CP litigation.Item Open Access A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensus statement(BMJ PUBLISHING GROUP, 1999) MacLennan, A.Item Metadata only Antenatal causes of cerebral palsy: associations between inherited thrombophilias, viral and bacterial infection, and inherited susceptibility to infection(Lippincott Williams & Wilkins, 2003) Gibson, C.; MacLennan, A.; Goldwater, P.; Dekker, G.Cerebral palsy rates of 2 in every 1,000 births have varied little over the last 40 years, despite improvements in obstetric care. In the past, cerebral palsy was thought to be due to poor obstetric care and management; however, epidemiological studies have refuted this, suggesting that there is usually an antenatal timing to the neuropathology of cerebral palsy. There are many known risk factors for cerebral palsy, including multiple gestation, prematurity, and low birth weight. Recently, intrauterine infection, maternal pyrexia, and the presence of thrombophilic disorders (thrombophilia) have been identified as major risk factors for subsequent cerebral palsy. This review examines the links between intrauterine infection, the fetal inflammatory response, and thrombophilia as possible causes of cerebral palsy. The interactions of viral or bacterial infections during pregnancy, normal or abnormal fetal cytokine responses, and hereditary fetal thrombophilias as antenatal causes of the neuropathology of cerebral palsy are now areas of research priority. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the condition cerebral palsy, list the risk factors for the development of cerebral palsy, outline the ultrasound findings associated with cerebral palsy, and point out other conditions associated with cerebral palsy.Item Metadata only Apolipoprotein E and the genetics of cerebral palsy - where to next?(Cambridge Univ Press, 2013) O'Callaghan, M.This commentary is on the original article by Lien et al on pages 372–377of this issue.Item Metadata only Apolipoprotein E genotype is not associated with cerebral palsy(Wiley, 2009) McMichael, G.; Gibson, C.; MacLennan, A.; Goldwater, P.; Haan, E.; Priest, K.; Dekker, G.; International Cerebral Palsy Conference (3rd : 2009 : Sydney, New South Wales); Robinson InstituteItem Metadata only Association between apolipoprotein E genotype and cerebral palsy is not confirmed in a caucasian population(Springer, 2008) McMichael, G.; Gibson, C.; Goldwater, P.; Haan, E.; Priest, K.; Dekker, G.; MacLennan, A.Apolipoprotein E (APOE) plays a significant role in lipid metabolism and has been implicated in the growth and repair of injured neurons. Two small studies have suggested an association between APOE genotype and cerebral palsy. We investigated if APOE genotype is associated with an increased risk for cerebral palsy, influences the type of cerebral palsy or interacts with prenatal viral infection to influence risk of cerebral palsy. The population-based case-control study comprised newborn screening cards of 443 Caucasian patients with cerebral palsy and 883 Caucasian matched controls. APOE genotyping was performed on DNA extracted from dried blood spots. Allelic and genotypic frequencies did not differ between cases and controls and combined frequencies were 0.10 (ε2), 0.76 (ε3), 0.14 (ε4), 0.03 (ε2/ε2), 0.10 (ε2/ε3), 0.03 (ε2/ε4), 0.02 (ε4/ε4), 0.21 (ε3/ε4), 0.61 (ε3/ε3). APOE genotype was correlated with cerebral palsy, type of cerebral palsy, gestation at birth and the presence of viral nucleic acids detected in previous work. Analysis by gestational age (all gestational ages, ≥37, 32–36 and <32 weeks) and type of cerebral palsy (all types, diplegia, hemiplegia and quadriplegia) showed no association between APOE genotype and cerebral palsy in this Caucasian population. An association between prenatal viral infection, APOE genotype and cerebral palsy was not demonstrated. These results did not confirm an association between APOE genotype, cerebral palsy, type of cerebral palsy and prenatal infection in a Caucasian population. Given the low frequency of APOE ε2 and some of the heterozygote and homozygote combinations in this study, a larger study is assessing this further.Item Metadata only Associations between fetal inherited thrombophilia and adverse pregnancy outcomes(Mosby Inc, 2006) Gibson, C.; MacLennan, A.; Janssen, N.; Kist, W.; Hague, W.; Haan, E.; Goldwater, P.; Priest, K.; Dekker, G.Objective: The purpose of this study was to investigate associations between fetal inherited thrombophilia and adverse pregnancy outcomes, including pregnancy-induced hypertensive disorders (PIHD), antepartum hemorrhage (APH), small-for-gestational age <10th percentile (SGA), and preterm birth (PTB). Study design: Seven hundred and seventeen cases and 609 controls were genotyped for Factor V Leiden (FVL, G1691A), Prothrombin gene mutation (PGM, G20210A), and Methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C using DNA from newborn screening cards. Results: For babies born <28 weeks' gestation, PGM was associated with an increased risk of SGA (OR 6.40, 95%CI 1.66-24.71) and APH with SGA (OR 6.35, 95%CI 1.63-24.75). Homozygous MTHFR A1298C was associated with an increased risk of SGA for babies born 28-31 weeks gestation (OR 4.00, 95%CI 1.04-15.37), and with APH and SGA for babies born <32 weeks' gestation (OR 3.57, 95%CI 1.09-11.66). Homozygous MTHFR C677T was associated with a reduced risk of PTB and SGA (OR 0.52, 95%CI 0.28-0.96) for babies born 32 to 36 weeks' gestation. Homozygous FVL decreased the risk of PTB <32 weeks' gestation (OR 0.55, 95%CI 0.31-0.98). Conclusion: Fetal thrombophilic polymorphisms may be related to adverse pregnancy outcomes, in particular SGA.Item Metadata only Associations between inherited thrombophilias, gestational age, and cerebral palsy(Mosby Inc, 2005) Gibson, C.; MacLennan, A.; Hague, W.; Haan, E.; Priest, K.; Chan, A.; Dekker, G.Objective: This study was undertaken to investigate associations between inherited thrombophilic polymorphisms and cerebral palsy (CP) in a large case-control study. Study design: This is a population-based case-control study. Genomic DNA from newborn screening cards of 443 white CP cases and 883 white controls was tested for factor V Leiden (FVL, G1691A), prothrombin gene mutation (PGM, G20210A), and methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C. Results: MTHFR C677T was associated with an increased risk of developing any CP (32-36 weeks' gestation, homozygous odds ratio [OR] 2.55, 95% CI 1.12-5.74; heterozygous OR 1.91, 95% CI 1.01-3.66). MTHFR C677T was also associated with diplegia at both less than 32 weeks' gestation (homozygous OR 2.76, 95% CI 1.21-6.12) and all gestations (heterozygous OR 1.58 95%, CI 1.02-2.45). For children less than 32 weeks, FVL homozygosity may be associated with an increase in the risk of developing quadriplegia (OR 9.12, 95% CI 0.86-53.71). MTHFR A1298C (heterozygous) was associated with a reduced risk of diplegia developing at 32 to 36 weeks' gestation (OR 0.16, 95% CI 0.02-0.70). There were no associations between any type of CP and thrombophilia for children born 37 weeks or greater. Heterozygous PGM and homozygous MTHFR C677T combined were associated with quadriplegia at all gestational ages (OR 5.33, 95% CI 1.06-23.25). Conclusion: MTHFR C677T approximately doubles the risk of CP in preterm infants. A combination of homozygous MTHFR C677T and heterozygous PGM increases the risk of quadriplegia 5-fold at all gestational ages.Item Open Access Brain damage and maternal medication(Mosby Inc, 2013) O'Callaghan, M.; MacLennan, A.Item Metadata only Candidate Genes and Cerebral Palsy: A Population-Based Study(Amer Acad Pediatrics, 2008) Gibson, C.; MacLennan, A.; Dekker, G.; Goldwater, P.; Sullivan, T.; Munroe, D.; Tsang, S.; Stewart, C.; Nelson, K.Objective
The objective of this study was to examine whether selected genetic polymorphisms in the infant are associated with later-diagnosed cerebral palsy.Methods
A population-based case-control study was conducted of 28 single-nucleotide polymorphisms measured in newborn screening blood spots. A total of 413 children with later-diagnosed cerebral palsy were born to white women in South Australia in 1986-1999, and there were 856 control children. Distributions of genotypic frequencies were examined in total cerebral palsy, in gestational age groups, and by types of cerebral palsy and gender. Genotyping was performed by using a TaqMan assay.Results
For inducible nitric-oxide synthase, possession of the T allele was more common in all children with cerebral palsy and for heterozygotes who were born at term. For lymphotoxin alpha, homozygous variant status was associated with risk for cerebral palsy and with spastic hemiplegic or quadriplegic cerebral palsy. Among term infants, heterozygosity for the endothelial protein C receptor single-nucleotide polymorphism was more frequent in children with cerebral palsy. In preterm infants, the variant A allele of interleukin 8 and heterozygosity for the beta-2 adrenergic receptor were associated with cerebral palsy risk. Interleukin 8 heterozygote status was associated with spastic diplegia. Variants of several genes were associated with cerebral palsy in girls but not in boys.Conclusions
Two of the 28 single-nucleotide polymorphisms examined were associated with all types of spastic cerebral palsy in both gestational age groups and others with cerebral palsy in gestational age or cerebral palsy subgroups. Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy.Item Metadata only Cerebral palsy and clinical negligence litigation: a cohort study(Blackwell Publishing Ltd, 2004) MacLennan, A.; Robinson, J.Item Metadata only Cerebral palsy and the application of the international criteria for acute intrapartum hypoxia(Lippincott Williams & Wilkins, 2006) Strijbis, E.; Oudman, I.; van Essen, P.; MacLennan, A.Objective
To apply objective criteria for the identification of acute intrapartum hypoxia in a cohort of cerebral palsy cases and to identify other cerebral palsy-related pathologies.Methods
A cohort of all 235 neonates with cerebral palsy from a single Australian tertiary care center born between 1986 and 2003. Cases were identified from the South Australian Cerebral Palsy Register. Maternal and pediatric case notes were audited with application of the 2003 American College of Obstetricians and Gynecologists/American Academy of Pediatrics criteria to identify acute intrapartum hypoxia.Results
Data were available for analysis in 213 cases (91%). Major antenatal or pediatric cerebral palsy-related pathologies were identified in 98.1% of all these cases. An isolated acute intrapartum hypoxic event was defined as likely in only 2 of the 46 neonates born at term and none born preterm. Neonatal nucleated red blood cell counts were often high in neonates born preterm and following antenatal pathologies.Conclusion
Cerebral palsy was seldom preceded by acute intrapartum hypoxia but antenatal cerebral palsy-related pathologies are often detectable. The objective American College of Obstetricians and Gynecologists/American Academy of Pediatrics criteria are useful to audit cerebral palsy causation and exclude primary intrapartum hypoxia.Level of evidence
II-3.Item Metadata only Cerebral palsy litigation - Reply(Amer Medical Assoc, 2006) MacLennan, A.; Nelson, K.; Hankins, G.; Speer, M.Item Metadata only Cerebral palsy – genomic susceptibility and environmental triggers(Wiley, 2009) MacLennan, A.; International Cerebral Palsy Conference (3rd : 2009 : Sydney, New South Wales); Robinson InstituteItem Metadata only Cerebral palsy – Is it in your genes? Genetic susceptibility and environmental risk factors(Wiley, 2012) MacLennan, A.; Biennial Conference of the Australasian Academy of Cerebral Palsy & Developmental Medicine (6th : 2012 : Brisbane, Australia); Robinson InstituteItem Metadata only Cesarean delivery and cerebral palsy: A systematic review and meta-analysis(Lippincott Williams & Wilkins, 2013) O'Callaghan, M.; MacLennan, A.; Robinson InstituteOBJECTIVE: To examine the association of cesarean delivery and cerebral palsy using a systematic literature review and meta-analysis. DATA SOURCES: MEDLINE, Embase, and ClinicalTrials. gov were systematically searched for articles relating to cerebral palsy and cesarean delivery from inception until December 2012. Only articles reporting confirmed cases of cerebral palsy were included. Meta-analysis was used to assess combined results and also the following subgroups: emergency cesarean; elective cesarean; term delivery; preterm delivery; and delivery of breech-presenting newborns. METHODS OF STUDY SELECTION: Literature searches returned 1,874 articles with 58 considered in full. Studies were selected if they reported an endpoint of cerebral palsy, an intervention or risk of cesarean delivery, were in English, and gave sufficient details to perform meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Nine case–control and four cohort studies were included in the overall analysis. Meta-analysis showed no overall association of cesarean delivery with cerebral palsy (odds ratio [OR] 1.29; 95% confidence interval [CI] 0.92–1.79; 3,810 case group participants and 1,692,580 control group participants). Emergency cesarean delivery was associated with increased risk of cerebral palsy (OR 2.17; 95% CI 1.58–2.98), whereas there was no significant association between elective cesarean delivery and cerebral palsy (OR 0.81; 95% CI 0.41–1.58). Any type of cesarean delivery (elective or emergency) for term newborns was associated with cerebral palsy (OR 1.6; 95% CI 1.05–2.44), whereas there was no association between any type of cesarean delivery and cerebral palsy in preterm newborns (OR 0.81; 95% CI 0.47–1.40). Cesarean delivery did not significantly modify cerebral palsy risk for breech-presenting newborns (OR 0.51; 95% CI 0.13–2.05).Item Metadata only Comparison of DNA extraction methods from small samples of newborn screening cards suitable for retrospective perinatal viral research(The Association of Biomolecular Resource Facilities, 2011) McMichael, G.; Highet, A.; Gibson, C.; Goldwater, P.; O'Callaghan, M.; Alvino, E.; MacLennan, A.; South Australian Cerebral Palsy Research GroupReliable detection of viral DNA in stored newborn screening cards (NSC) would give important insight into possible silent infection during pregnancy and around birth. We sought a DNA extraction method with sufficient sensitivity to detect low copy numbers of viral DNA from small punch samples of NSC. Blank NSC were spotted with seronegative EDTA-blood and seropositive EBV EDTA-blood. DNA was extracted with commercial and noncommercial DNA extraction methods and quantified on a spectrofluorometer using a PicoGreen dsDNA quantification kit. Serial dilutions of purified viral DNA controls determined the sensitivity of the amplification protocol, and seropositive EBV EDTA-blood amplified by nested PCR (nPCR) validated the DNA extraction methods. There were considerable differences between the commercial and noncommercial DNA extraction methods (P=0.014; P=0.016). Commercial kits compared favorably, but the QIamp DNA micro kit with an added forensic filter step was marginally more sensitive. The mean DNA yield from this method was 3 ng/μl. The limit of detection was 10 viral genome copies in a 50-μl reaction. EBV nPCR detection in neat and 1:10 diluted DNA extracts could be replicated reliably. We conclude that the QIamp Micro DNA extraction method with the added forensic spin-filter step was suitable for retrospective DNA viral assays from NSC.Item Metadata only CP or not CP? A review of diagnoses in a cerebral palsy register(Elsevier Science Inc, 2010) Zarrinkalam, R.; Russo, R.; Gibson, C.; van Essen, P.; Peek, A.; Haan, E.The purpose of this study was to document the inaccuracy rate of diagnosis of cerebral palsy recorded on the South Australian Cerebral Palsy Register. A total of 402 children born in South Australia from 1993 to 2002 and notified to the Register as having cerebral palsy were identified through the Register database, and 21 children (5.2%) were later identified to have a noncerebral palsy diagnosis. Of these, 5 had either a metabolic or a neurodegenerative disorder and 2 had a syndromic disorder (1 Joubert syndrome and 1 Sotos syndrome); the remaining 14 children had one of the following final diagnoses: developmental delay, gross motor delay, perinatal myositis, spinal subdural and subarachnoid arteriovenous malformation, and Erb's palsy. In 16 of 21 children (76%), the diagnosis was changed at 5 years of age or older. Studies based on population registers may need to take into account the possibility of misclassification, estimated to be at least 5.2% in this study. A complete clinical assessment at the time of diagnosis followed by regular reassessment would enable the clinician to exclude children with alternative diagnoses, which has important implications for clinical management and research based on cerebral palsy registers.Item Metadata only Cytomegalovirus and Epstein–Barr virus may be associated with some cases of cerebral palsy(Taylor & Francis Ltd, 2012) McMichael, G.; MacLennan, A.; Gibson, C.; Alvino, E.; Goldwater, P.; Haan, E.; Dekker, G.Objective: Intrauterine infection is a risk factor for cerebral palsy. Previous work reported a high frequency of viral DNA in newborn screening cards from cerebral palsy cases and controls possibly due to contamination. Methods: Retrospective case-control study using improved methodologies to minimize contamination during PCR-based detection of viral DNA sequences. Newborn screening cards of 339 Caucasian children with cerebral palsy and 594 controls were examined. Viruses tested were herpes simplex viruses 1 and 2 (HSV1 and 2), varicella zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpes viruses 6, 7 and 8 (HHV6, HHV7 and HHV8), and parvovirus B19. Genotyping was performed on DNA extracted from dried blood spots. Results: CMV and EBV were detected in 5 (1.5%) and 3 (0.9%) of 339 cases, respectively, but not in controls (p = 0.047 and 0.006). Frequencies of detection of the other viruses examined were similar for cases and controls. DNA from at least one of the nine viruses tested was found in 4.4% of cases and 3.1% of controls [OR 1.4 95% CI (0.71–2.76)]. Conclusion: Evidence of congenital viral infection was uncommon in cases of cerebral palsy and controls. However, CMV and EBV were significantly associated with cerebral palsy.Item Metadata only DNA from Buccal Swabs Suitable for High-Throughput SNP Multiplex Analysis(The Association of Biomolecular Resource Facilities, 2009) McMichael, G.; Gibson, C.; O'Callaghan, M.; Goldwater, P.; Dekker, G.; Haan, E.; MacLennan, A.We sought a convenient and reliable method for collection of genetic material that is inexpensive and noninvasive and suitable for self-collection and mailing and a compatible, commercial DNA extraction protocol to meet quantitative and qualitative requirements for high-throughput single nucleotide polymorphism (SNP) multiplex analysis on an automated platform. Buccal swabs were collected from 34 individuals as part of a pilot study to test commercially available buccal swabs and DNA extraction kits. DNA was quantified on a spectrofluorometer with Picogreen dsDNA prior to testing the DNA integrity with predesigned SNP multiplex assays. Based on the pilot study results, the Catch-All swabs and Isohelix buccal DNA isolation kit were selected for our high-throughput application and extended to a further 1140 samples as part of a large cohort study. The average DNA yield in the pilot study (n=34) was 1.94 μg ± 0.54 with a 94% genotyping pass rate. For the high-throughput application (n=1140), the average DNA yield was 2.44 μg ± 1.74 with a ≥93% genotyping pass rate. The Catch-All buccal swabs are a convenient and cost-effective alternative to blood sampling. Combined with the Isohelix buccal DNA isolation kit, they provided DNA of sufficient quantity and quality for high-throughput SNP multiplex analysis.
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