Peripheral blood cell microRNA quantification during the first trimester predicts preeclampsia: Proof of concept

Abstract

ObjectiveWe investigated the capacity of microRNAs isolated from peripheral blood buffy coat collected late during the first trimester to predict preeclampsia.Study designThe cohort study comprised 48 pregnant women with the following pregnancy outcomes: 8 preeclampsia and 40 with normal delivery outcomes. Quantitative rtPCR was performed on a panel of 30 microRNAs from buffy coat samples drawn at a mean of 12.7±0.5 weeks gestation. MicroRNA Risk Scores were calculated and AUC-ROC calculations derived.ResultsThe AUC-ROC for preeclampsia risk was 0.91 (p<0.0001). When women with normal delivery and high-risk background (those with SLE/APS, chronic hypertension and/or Type 2 Diabetes) were compared to women who developed preeclampsia but with a normal risk background (without these mentioned risk factors), preeclampsia was still predicted with an AUC-ROC of 0.92 (p<0.0001).ConclusionMicroRNA quantification of peripheral immune cell microRNA provides sensitive and specific prediction of preeclampsia in the first trimester of pregnant women. With this study, we extend the range during which disorders of the placental bed may be predicted from early to the end of the first trimester. This study confirms that buffy coat may be used as a sample preparation.

MicroRNAs isolated from peripheral blood in the first trimester predict spontaneous preterm birth

“…The results of the current research are consistent with previous studies published by our group that have demonstrated that peripheral blood cell microRNA obtained during the first trimester of pregnancy predicts risk of preterm delivery [34], spontaneous abortion [37,33], and preeclampsia [32]. In addition, the current study confirms the usefulness of peripheral blood cell microRNA as biomarkers identifying risk of preterm birth early in the first trimester.…”

“…Winger and Reed suggested an alternative to interrogation of plasma components. They hypothesized that interrogation of the maternal immune cell component of the placental bed would offer at least two significant advantages: first, the method would eliminate the interrogation of an intermediary organ, the placenta, rather than direct interrogation of the underlying pathology in the placental bed and, second, the method would allow recognition of the underlying pathology at an earlier time point [ 32 – 34 , 37 ]. However, investigation of the placental bed is more challenging than examination of placental shed components.…”

“…Forty-five microRNAs were selected for quantification ( Table 1 , rows 1–45) along with three controls ( Table 1 , rows 46–48). Thirty of these microRNAs were retained from our previous studies ( Table 1 , rows 1–30) [ 32 – 34 ] with five added microRNA sequences representing alternate dominant RNA arms (opposite 5' or 3' arm) of the original 30 microRNAs ( Table 1 , rows 31–35). In addition, 10 additional microRNA sequences were selected ( Table 1 , rows 31–45) based on their ability to identify risk of adverse pregnancy outcome in an African population (unpublished data.…”

“…Previous studies by Winger and Reed unexpectedly identified differentially expressed microRNAs within peripheral blood cells between patients who experienced late pregnancy disorders and those that experienced healthy term births [32,33]. The blood samples were originally collected during the first trimester in a study directed to correlation of blood cell microRNA with functional assays of immune function.…”

Preeclampsia – Prediction and Monitoring Factors

“…In order to assess the possibility of prediction of preeclampsia by analyzing microRNAs from peripheral blood buffy coat samples of pregnant women, Winger and coauthors investigated 30 microRNAs (43). Authors performed qRT-PCR analysis on samples of 48 pregnant women collected during first trimester of pregnancy (11±13 weeks gestation), of whom 8 had preeclampsia.…”