Longitudinal 8-Epi-Prostaglandin F2-Alpha and Angiogenic Profile Mediator Evaluation during Pregnancy in Women with Suspected or Confirmed Pre-eclampsia

Background: In this exploratory study, we aimed to evaluate the dynamics of angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), soluble Endoglin (sEng), and sFlt-1/PlGF, PlGF/sFlt-1, and sEng/PlGF ratios] and oxidative stress [8-epi-prostaglandin F2 alpha (8-epi-PGF2α) and 8-epi-PGF2α/PlGF ratio] mediator levels in women with suspected or confirmed pre-eclampsia (PE) at least two times during pregnancy. We also wanted to identify the possible correlations between 8-epi-PGF2α and angiogenic mediator levels at the time of inclusion of pregnant women. Methods: We included 40 pregnant women with suspected or confirmed PE, with a mean age of 29 years (range between 18 and 41 years) and gestational age between 18 and 28 weeks at inclusion in this study. The Enzyme-Linked Immunosorbent Assay (ELISA) method to measure the levels of serum angiogenic and oxidative stress mediators was used. Results: The evaluation of baseline sFlt-1/PlGF ratios using a cut-off of 38 suggested that 25 pregnant women had a sFlt-1/PlGF ratio of >38 (sFlt-1/PlGF ratio of >38 group) and 15 had a sFlt-1/PlGF ratio of ≤38 (sFlt-1/PlGF ratio of ≤38 group). The increases in sFlt-1/PlGF ratio in the sFlt-1/PlGF ratio of >38 group were caused by both an increase in sFlt-1 (2.04-fold) and a decrease in PlGF levels (2.55-fold). The 8-epi-PGF2α median levels were higher in the sFlt-1/PlGF ratio of >38 group (1.62-fold). During follow-up after pregnancy, we observed that the mean values of sFlt-1 and sEng and the median values of 8-epi-PGF2α and sFlt-1/PlGF, sEng/PlGF, and 8-epi-PGF2α/PlGF ratios increased directly proportional to gestational age for each measurement time until delivery in both groups. For five women who had a sFlt-1/PlGF ratio ≤38 at inclusion, sFlt-1/PlGF ratio was observed to increase to >38 later in pregnancy. We observed that, in the sFlt-1/PlGF ratio >38 group, baseline 8-epi-PGF2α levels better correlated with angiogenic mediator levels. Conclusions: Our study shows that 33.33% of pregnant women evaluated for suspected or confirmed PE with a sFlt-1/PlGF ratio of ≤38 displayed a rise in sFlt-1/PlGF ratio in subsequent weeks. In addition, together with angiogenic mediators, 8-epi-PGF2 α can be utilized as an independent predictor factor to help clinicians identify or predict which pregnant women will develop PE