dr philip baker

Our overall objective is to develop a clinically robust predictive blood test for pre-eclampsia, using innovative technologies and utilising novel metabolite and protein biomarkers. The development of such a personalized medicine approach, that offers first time mothers accurate risk assessment for pre-eclampsia, will radically impact the provision of antenatal care, and will reduce the clinical complications of this leading cause of maternal death.

Pre-eclampsia: Almost 1 in 20 of these pregnancies are complicated by pre-eclampsia. This is a disease of late pregnancy characterized by the concomitant occurrence of hypertension and proteinuria. The condition is associated globally with 70,000-80,000 maternal and over 500,000 infant deaths annually. Additionally, epidemiological studies have demonstrated that pre-eclampsia is associated with an increased risk of cardiovascular and metabolic diseases later in the mother’s life. A quarter of the babies born to mothers with pre-eclampsia are growth restricted and a third are premature. The child may have problems with neurocognitive development that can result in mild learning difficulties through to severe disabilities. Being born growth restricted also predisposes the child to cardiovascular disease as an adult.[

In pre-eclampsia 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. Indeed the World Health Organization’s (WHO) systematic review assessed the usefulness of clinical, biophysical, and biochemical tests in the prediction of pre-eclampsia and concluded that there is no cost effective or reliable screening test for pre-eclampsia. As a consequence, without a screening test, clinicians are unable to offer either targeted surveillance or potential preventative therapies to those at greatest risk.

Metabolomics and pre-eclampsia: 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.

Professors Philip Baker and Louise Kenny have pioneered the clinical exploitation of metabolomic technology for patient benefit. A decade-long collaboration funded by Science Foundation Ireland, British Heart Foundation, Wellcome Trust, and Enterprise Ireland 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. Metabolomic Diagnostics Ltd. is the innovative SME leading the commercialization of this breakthrough technology and the R&D of a prototype test utilising a platform capable of delivering robust, high throughput and economically viable clinical screening.  Liquid Chromatography Triple Quadrupole Mass Spectroscopy (LC-QQQ-MS) has been selected as the platform of choice. LC-QQQ-MS offers a single platform with a one-stage sample preparation and is amenable to the addition of robotic liquid handling. Moreover, LC-QQQ-MS facilitates quantification of biomarkers, is cheaper, is more robust, and has detection limits that are lower than for other mass spectrometry techniques. Consequently, LC-QQQ-MS technology is already being used in clinical labs around the world, for example in newborn screening programs\; this will streamline regulatory approval for adaptation for use in pre-eclampsia.