Liggins Institute special seminar: The key to pre-eclampsia and fetal growth restriction: Novel strategies Event as iCalendar

Pre-eclampsia (PE) and fetal growth restriction (FGR) complicate up to 10% of pregnancies and are responsible for substantial maternal and fetal morbidity. The effects of PE and FGR are not limited to early life; survivors are at greater risk of cerebral palsy and neurodevelopmental delay. Furthermore, babies that are growth restricted have increased risk of developing cardiovascular disease, chronic hypertension, diabetes and schizophrenia in adulthood.

The aetiology of PE/FGR is multifactorial and remains poorly defined. There are demonstrable biologically active circulating factors that are apparent well before the clinical presentation of the disease; nevertheless, there are currently no early pregnancy predictive tests for pre-eclampsia. Numerous candidate biomarkers (>200 studies so far) have been proposed for prediction of disease, including placental hormones, angiogenic factors, and lipids. However, none (nor any combination) has emerged with the requisite specificity and sensitivity to be of clinical use. As a consequence, without a screening test, clinicians are unable to offer either targeted surveillance or potential preventative therapies to those at greatest risk.

Our approach to identifying biomarkers has been to focus on metabolic changes in plasma. Metabolomic profiling is a powerful strategy for investigating the low molecular weight (bio)chemicals (metabolites) present in the metabolome of a cell, tissue, or organism. Its position as the final downstream product of gene expression enables the provision of a high-resolution multifactorial phenotypic signature of disease aetiology, manifestation, or pathophysiology. A decade-long investigation of the metabolomics of PE led to the discovery and validation of a unique set of metabolites, which, in combination with limited clinical data, has the potential to accurately predict pre-eclampsia in early pregnancy with unprecedented sensitivity and specificity. Our initial work used Ultra Performance Liquid Chromatography-Mass Spectrometry but we have progressed to a platform capable of delivering robust, high throughput and economically viable clinical screening. Liquid Chromatography Triple Quadrupole Mass Spectroscopy (LC-QQQ-MS), the platform of choice, offers a single platform with a one-stage sample preparation and is amenable to the addition of robotic liquid handling.

There is no curative treatment for PE/FGR and the only therapy is early delivery, which has its own risks of mortality and morbidity. The development of effective predictive tests should facilitate the new therapeutic strategies; despite the heavy burden of PE/FGR, there have been few therapeutic advances; only one new class of drug has been licensed for obstetric conditions in the last 20 years. We have developed treatments for PE/FGR by screening potential therapies in existing, and novel, mouse models of disease. Interventions that rescue utero- and fetoplacental vascular development and function in PE/FGR have immense potential for treatment of these serious pregnancy complications and are the focus of our research.

Professor  Philip Baker

Professor of Obstetrics & Gynecology, University of Alberta, Edmonton, Canada Senior Advisor on international health/science initiatives, Office of the Provost, University of Alberta Consultant Obstetrician Royal Alex Hospital, Edmonton Professor of Maternal & Fetal Health, University of Manchester (Visiting Appointment)

For more information please contact:

Eleanor Surtida

Directorate Administrator

Liggins Institute, University of Auckland

Email:

b.surtida@auckland.ac.nz

Phone: (09) 923 1966