Paediatrics (RCH) - Theses

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    The Role of Maternal Serum Biomarkers in the Aetiology of Cerebral Palsy
    Peris, Monique Caroline ( 2023-02)
    Background CP affects 1 in 700 infants in Australia and is a major cause of physical disability in children. Long term psychological and financial impacts are associated with children with CP and their families. Despite its prevalence, limited effective prevention strategies exist due to the complex aetiology of CP, extensive timeframe over which injury can occur and diagnosis which is often delayed from the time of injury. The Australian Cerebral Palsy Register Report has identified that an estimated 94% of cases of cerebral palsy originate in the antenatal and perinatal period, which draws attention to this important time in the developing brain. Routine maternal serum screening testing in Victoria currently encompasses combined testing of biomarkers to predict the likelihood of congenital and chromosomal anomalies. PAPP-A, hCG, AFP, uE3 and inhibin are well recognised markers of placental integrity used in antenatal testing. Adverse pregnancy outcomes associated with placental dysfunction are also known to increase the risk of CP. Aims and Methods The aims of this research were twofold. Firstly, to determine if first and second trimester biomarkers used in current maternal serum screening are associated with pregnancies resulting in an infant with CP. Secondly, to evaluate what maternal serum biomarkers tell us about aetiological pathways of CP in the antenatal period. The methods used to investigate these aims were: 1. Data linkage between the Victorian Cerebral Palsy Register (VCPR) and Maternal Serum Screening service of the Victorian Clinical Genetics Service (VCGS) linking CP cases with their antenatal screening blood tests. Analysis of the association between CP cases and non CP controls using a retrospective case control study design and predictive analysis. 2. Systematic review of the role of hCG in pregnancy to determine how this biomarker contributes to understanding of aetiological classifications of CP in the antenatal period. Results Data linkage resulted in 435 first trimester and 129 second trimester CP cases who underwent maternal serum screening. Low first trimester levels of PAPP-A and beta-hCG and high second trimester levels of AFP and inhibin were associated with pregnancies that resulted in an infant with CP. Despite this all biomarkers showed poor predictive ability as a diagnostic test for CP. Abnormal biomarker levels were associated with adverse pregnancy outcomes known to increase the risk of CP such as prematurity, perinatal hypoxia-ischaemia and congenital anomalies. The systematic review found an association between placenta mediated pregnancy complications and hCG, highlighting the importance of placental biomarkers as markers of placental dysfunction and integrity. Conclusion First and second trimester biomarkers are associated with the subsequent development of CP, suggesting placental dysfunction as part of the causal pathways in these cases. Improving intervention and prevention relies on improving understanding of the role of the placenta in the aetiology of CP.
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    Proximal femoral osteotomy in children and adolescents with cerebral palsy
    Zhou, Leena ( 2018)
    Background Cerebral Palsy (CP) is the most common cause of physical disability affecting children in developed countries. Approximately one third of children with CP may develop hip displacement. Non-ambulant children at Gross Motor Function Classification System (GMFCS) levels IV and V are at highest risk. Without early detection through surveillance programs, hip displacement can progress to hip dislocation, which is frequently painful and negatively impacts health-related quality of life (HRQoL). Injections of Botulinum Neurotoxin A (BoNT-A) have no role, and soft tissue surgery has a limited role in preventing hip displacement in non-ambulant children with CP. Bony hip reconstruction surgery such as a proximal femoral osteotomy (PFO) is effective in stabilising the hip and HRQoL. PFOs include Femoral Derotation Osteotomies (FDO) which aim to improve the gait of an ambulant child (GMFCS I-III), and Varus Derotation Osteotomies (VDRO) which aim to contain the hips in non-ambulant children (GMFCS IV-V). However, PFOs can carry high risks, especially in children with medical co-morbidities such as respiratory disease, nutritional deficiencies, hypertonia and osteopenia. Aim This thesis involved a series of three studies, which aimed to expand our knowledge of the trainee learning curve, outcomes and adverse events relating to PFO in children and adolescents with CP. Method and Results A new implant combining locking and cannulated technology (Locking Cannulated Blade Plate, LCBP) was recently developed for use in PFO. A pilot study was performed on the first 25 patients who had surgery with the LCBP, at the Royal Children’s Hospital (RCH), Melbourne. This study established safety for use in children as young as three, with weights as low as eleven kilograms. A further prospective, parallel cohort study of 90 consecutive children with CP was conducted to compare the LCBP against with existing non-cannulated, non-locking implant (Angled Blade Plate, ABP). Technical and radiological outcomes of surgery were similar between implants. However, the surgical technique was reported by trainees to be easier when using the LCBP, with less technical errors. Approximately 60 percent of the children experienced minor adverse events including: constipation, inadequate pain control, and respiratory compromise. However, a CP specific tool was not available to classify the severity of events. Study three was performed to clarify the Modified Clavien-Dindo (MCD) system for lower limb surgery in children with CP and test its’ reliability for classifying adverse events. Very good reliability was demonstrated amongst members within a multidisciplinary team. Conclusion Novel findings from these studies may help improve the safety and efficacy of the management of hip displacement in children with CP. Further research should address the long-term outcomes of PFO in children with CP, evaluate the validity of the MCD for children in CP and determine if the MCD can be embedded in the electronic medical records (EMR) as a routine tool for audit and clinical research.
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    Scoliosis in children with cerebral palsy: a population based study
    Ang, Soon Ghee ( 2015)
    Introduction Scoliosis is the most common spinal deformity in children with cerebral palsy. Previous published studies have been based on institutionalised patients and not on a total population of individuals with cerebral palsy. Methods This study was based on both prospective and retrospective cross-section analysis of 292 children identified from the Victorian Cerebral Palsy Register. These children were spread across GMFCS levels I–V. The children were assessed during their transition clinic appointment prior to exit from the Royal Children’s Hospital. The research looked at three main sections: clinical review for scoliosis, radiographic assessment of scoliosis, and CHQ and CPCHILD questionnaires survey. Cobb angles were measured by two experienced observers. Results If a Cobb angle of more than 10° was used, then 40% of patients were classified with scoliosis. By changing the definition of scoliosis in cerebral palsy to a Cobb angle greater than 40°, the prevalence of “clinically important scoliosis” was 12.7%. The majority of the severe curves occurred in children at GMFCS levels IV and V. As the GMFCS level increased, the mean Cobb angle increased. The mean score for the questionnaires decreased as the GMFCS level increased. Conclusion The CP scoliosis and the scores for the questionnaire were closely related to the GMFCS levels. The prevalence of CP scoliosis is overestimated in other studies. Our study shows the prevalence of CP scoliosis is 12.7% using a Cobb angle of more than 40°. Non-ambulant children are at high risk of developing scoliosis and formal spine surveillance should be considered.