Paediatrics (RCH) - Theses

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Type: Masters Research thesis × Subject: cerebral palsy × Author: Peris, Monique Caroline ×

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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.