While these initial reports utilized samples in a retrospectively collected biobank, we subsequently validated these findings in a large prospective cohort study. Among 782 asymptomatic women destined to miscarry, first trimester serum MIC-1 levels were significantly decreased at 63% of normal levels, whereas PAPP-A were only 23% of normal values. Importantly, at a fixed 10% false positive rate, a test combining MIC-1 and PAPP-A yielded 63% sensitivity and a 6.6 positive likelihood ratio in predicting miscarriage. While this predictive performance could be potentially further improved by the addition of other biomarkers, this already forms the platform of a promising biomarker test to predict miscarriage among asymptomatic women. Given these promising results, we set out to assess the ability of plasma MIC-1 and PAPP-A concentrations to predict miscarriage in a different population. Early AbMole Ascomycin pregnancy Assessment Units are clinical services managing patients in early pregnancy with potential complications. A common clinical presentation to EPAUs are women with symptoms of threatened miscarriage. We measured these analytes in a cohort of 462 women presenting to an EPAU in United Kingdom where an intrauterine fetal viability was confirmed at the same presentation. We examined the ability of MIC-1 and PAPP-A to predict miscarriage in this cohort. Given hCG is used clinically as an early pregnancy biomarker, we also measured this analyte. Previously, we had shown in a prospective study of an asymptomatic cohort in early pregnancy that MIC-1 and PAPPA may have promise as predictive biomarkers for subsequent miscarriage. To further examine this possibility, we undertook this present prospective study in a clinical relevant setting: women presenting to EPAU. Most were referred because they had symptoms of threatened miscarriage, meaning this population was different to the asymptomatic cohort examined in the previous study. In this study, we again confirmed low MIC-1 and PAPP-A concentrations in women with live fetuses are significantly associated with subsequent miscarriage. A number of groups have sought to identify a predictive biomarker that can be performed in early pregnancy to identify those with live fetuses whom will subsequently miscarry. However, an accurate, validated and predictive biomarker reaching the benchmark of clinical utility has yet to be described. 
We have previously reported serum Anandamide may be predictive in the situation of threatened miscarriage, although these findings require AbMole 12-O-Tiglylphorbol-13-isobutyrate verification. Muttukrishna et al. reported that among a cohort of 40 women who had a threatened miscarriage, sFlt-1 were significantly depressed among those who miscarried. However, the numbers in that cohort were modest, and no data on the performance of the test was presented meaning their findings also require verification. In a prospective study of 122 participants, Johns et al. concluded inhibin A was decreased among those who subsequently aborted, but the area under the receiver operating characteristic curve was somewhat modest. While MIC-1 levels were significantly decreased among those destined to miscarry, we were disappointed to find that it performs very modestly as a predictive biomarker test for miscarriage in this largely symptomatic cohort. Interestingly, the ability of MIC-1 to predict miscarriage appears substantially better when applied to an asymptomatic cohort compared to the present population presenting to the EPAU where a majority had symptoms of threatened miscarriage. There are a number of possible explanations for this rather surprising difference in our two independent prospective studies.