PROBLEM: Prior to the end of the first trimester, pathogenic mechanisms may commit pregnancies to adverse outcome such as pre-eclampsia and miscarriage. A long-term search for biomarkers predicting these adverse outcomes has not identified any that reliably succeed prior to the beginning of the second trimester. MicroRNAs, with their important role as regulators of signaling and metabolic pathways within living cells, may offer a new approach. METHODS: Optimal maternal PBMC microRNA markers were investigated using a series of sequential experiments, and 30 microRNAs were selected based on these results. Quantitative RT-PCR was then performed on these 30 microRNAs for 39 patients [19 healthy deliveries, 12 pre-eclampsia (seven late onset and five early onset) and eight miscarriages] during the first trimester of pregnancy. Results were scored, and their predictive values assessed. RESULTS: MicroRNA quantification in the early first trimester (mean 34.9 ± 19.2 days post-implantation) predicted miscarriage and late pre-eclampsia with a P value of P < 0.0001 and achieved an AUC of 0.90 for miscarriage and 0.90 for late pre-eclampsia. CONCLUSION: MicroRNA quantification of maternal blood cells offers the clinician a single test result that is simple to interpret and available much earlier in pregnancy than previously obtainable. In addition, it is the only early pregnancy marker, to date, that can successfully predict late pre-eclampsia. Although the studies that we report are preliminary, we hope that future research will build upon our discoveries and enhance the power of maternal cell microRNA to predict adverse pregnancy outcome in the clinic.
PROBLEM: Prior to the end of the first trimester, pathogenic mechanisms may commit pregnancies to adverse outcome such as pre-eclampsia and miscarriage. A long-term search for biomarkers predicting these adverse outcomes has not identified any that reliably succeed prior to the beginning of the second trimester. MicroRNAs, with their important role as regulators of signaling and metabolic pathways within living cells, may offer a new approach. METHODS: Optimal maternal PBMC microRNA markers were investigated using a series of sequential experiments, and 30 microRNAs were selected based on these results. Quantitative RT-PCR was then performed on these 30 microRNAs for 39 patients [19 healthy deliveries, 12 pre-eclampsia (seven late onset and five early onset) and eight miscarriages] during the first trimester of pregnancy. Results were scored, and their predictive values assessed. RESULTS: MicroRNA quantification in the early first trimester (mean 34.9 ± 19.2 days post-implantation) predicted miscarriage and late pre-eclampsia with a P value of P < 0.0001 and achieved an AUC of 0.90 for miscarriage and 0.90 for late pre-eclampsia. CONCLUSION: MicroRNA quantification of maternal blood cells offers the clinician a single test result that is simple to interpret and available much earlier in pregnancy than previously obtainable. In addition, it is the only early pregnancy marker, to date, that can successfully predict late pre-eclampsia. Although the studies that we report are preliminary, we hope that future research will build upon our discoveries and enhance the power of maternal cell microRNA to predict adverse pregnancy outcome in the clinic.