DALLAS – MicroRNA 210 is strongly associated with the presence of preeclampsia, and predicts the condition months prior to its onset, according to findings in a subset of women from a case-control study and women from a separate prospective cohort.
If validated as a reliable biomarker in larger studies, microRNA 210 (MIR210) could be used to risk-stratify women for development of hypertensive disorders of pregnancy, including preeclampsia, Dr. Michal A. Elovitz reported at the annual meeting of the Society for Maternal-Fetal Medicine.
The levels of MIR210, as well as levels of MIR517a and MIR517c, were first analyzed in 28 maternal serum samples from women with preeclampsia who were enrolled in the Preeclampsia: Mechanisms and Consequences study. The microRNA levels were compared with those from samples collected from 14 control patients without preeclampsia at the time of delivery. Samples in the cases were collected either at the time of diagnosis or at the time of delivery, said Dr. Elovitz of the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia.
The MIR517a and MIR517c levels did not differ between the groups, but MIR210 levels differed significantly in the cases and controls. In fact, each 1-unit increase in MIR210 was associated with a 9.5-fold increase in the odds of being a case vs. a control, Dr. Elovitz said, noting that controlling for race did not change the effect size, and that MIR210 had a "very high" predictive ability for being a case.
As expected, the gestational age at delivery was lower in the cases than the controls, but there were no significant differences in the rates of chronic hypertension, the number of African American women, and the number of fetuses with intrauterine growth restriction between the groups.
MIR210 levels also differed significantly in 38 cases and 57 controls from a separate prospective cohort of women undergoing integrated or sequential screening. Serum samples in that cohort were collected during the second trimester, at 15-17 weeks’ gestation.
Each 1-unit increase in MIR210 was associated in this cohort with a 2.9-fold increase in the likelihood of developing a hypertensive disease of pregnancy, Dr. Elovitz said, adding that the MIR210 in this population had "fair" predictive ability. When analysis was limited just to those who eventually developed preeclampsia, however, each 1-unit increase in MIR210 was associated with a 3.8-fold increase in the odds of developing preeclampsia.
Because there was such a wide range of MIR210 levels, she and her colleagues also looked at a 10-unit increase, and found that each of these units was associated with a 6.7-fold increase in the risk of preeclampsia. MIR210 in this scenario had a "fairly good" predictive value, she said.
In this portion of the study, no differences were seen between cases and controls with respect to gestational age at time of blood draw, number of African American women, rate of intrauterine fetal death, or rate of preterm birth at less than 37 weeks’ gestation.
MicroRNAs have emerged as critical players in many biological systems and in certain disease states, Dr. Elovitz explained.
MIR515a and MIR515c were included in the current analyses because they have previously been shown to be uniquely expressed in placental tissues, and increased in placental tissues from women with preeclampsia, compared with controls. MIR210 has been found to be very highly expressed in placental tissues, and is known to be highly involved in hypoxic conditions and to be a promising biomarker in other disease states, she said.
The current findings are important because preeclampsia is a leading cause of morbidity and mortality in pregnancy, and remains the leading cause of medically indicated preterm birth.
"Several randomized, controlled trials have failed to identify successful preventative strategies to decrease development of preeclampsia. Indeed, the pathogenesis of preeclampsia has not been revealed," she said, adding that consequently, the ability to identify those at risk is poor, and the ability to offer interventions based on the true pathogenesis of the disease has not been achieved.
The findings – although limited by the case-cohort design, small study populations, and the lack of a panel of microRNAs – suggest that MIR210 is a reliable biomarker for hypertensive disorders of pregnancy, including preeclampsia. The findings are strengthened by the focus on specific microRNAs and by the use of two cohorts.
"Further work is obviously necessary. We need to validate MIR210 as a reliable biomarker, and we need to unravel the role of MIR210 and other microRNAs in the pathogenesis of preeclampsia," Dr. Elovitz concluded.
Dr. Elovitz said she had no conflicts to disclose.