P88. Pre-eclampsia risk stratification for low risk 1st pregnancies: First results of a new LC-MS based multiplex metabolite assay

Introduction Screening for pre-eclampsia is a focus of prenatal care and is largely based on the use of clinical risk factors. However, current screening protocols are unfit to determine pre-eclampsia risk in 1st time pregnant women; biomarkers have the potential to address this unmet need. As single biomarkers have insufficient predictive accuracy, unbiased biomarker discoveries have been performed to identify panels of markers which when combined, have the potential pre-eclampsia prediction. Metabolite based solutions using mass spectrometry have gained significant interest as they have the potential to readily translate to clinical practice. Objectives To translate the discovery that blood-borne metabolite biomarkers stratify pregnant women early in pregnancy (∼15 weeks) to their risk of pre-eclampsia [1] into a commercial LC–MS based clinical assay. To pursue fit-for-purpose testing of the first version of the developed LC–MS pipeline followed by independent verification through a case:control study. Methods The analysis pipeline incorporated (1) a single step metabolite extraction, (2) multiplex LC-QqQ-MS assays for 40+ metabolites and (3) a dedicated data processing protocol. Case:control study testing utilised 15 weeks’ plasma samples of from 50 pregnant women who subsequently developed pre-eclampsia and 500 random control pregnancies. All participants are part of the SCOPE study [2] and were recruited in Cork, Ireland. Results For the 40+ metabolite assays: 62% had a %CV £ 15% and 82% had a %CV £ 25%. Univariate analyses using the ROC statistic showed that 7 of the metabolites tested had significant predictive power (lower limit 95% CI ROC-AUC [3] 0.5). Multivariate logistic regression analysis revealed particular combinations of metabolites which identified groups of women either at increased risk or at decreased risk for pre-eclampsia. Conclusion These findings underpin the potential of metabolite-centric multimarker panels to encapsulate a complex syndrome such as pre-eclampsia considerably in advance of any clinical manifestation. Further development steps will include performing additional case:control studies and subsequent clinical validation of this metabolite based test in the large scale European, multicentre phase IIa clinical study IMproved Pregnancy Outcomes by Early Detection (IMPROvED) which is currently recruiting 1st time pregnant women in 5 European countries [3] . Acknowledgment The authors gratefully acknowledge funding from the EU-HEALTH Project IMPROvED (305169) of the Seventh Framework Programme (FP7).