Spiral steroids as potential markers for pre-eclampsia: A pilot study

Pre-eclampsia is a condition that complicates 3-6% of pregnancies. At present, there is no FDA approved diagnostic method to evaluate risk or progression. We would like to report our observation of elevated levels of the spiral steroid phosphoester precursor in patients with pre-eclampsia. Samples from 20 normotensive pregnant women and from 20 women with pre-eclampsia were purchased from Global Alliance for the Prevention of Prematurity and Stillbirth (GAPPS). After addition of miltefosine (hexadecyl phosphocholine) as an internal control, each sample was extracted and evaluated by tandem MS. The method detected 2 spiral steroid phosphoesters and their common precursor. For each mass ion, the ion counts obtained were compared to the ion counts of miltefosine. The samples from the normotensive women were used to establish the mean and standard deviation. Then, Z-scores were determined for each of the serum components. Of the samples from the women with pre-eclampsia, 12 of 19 (63%) samples had Z-scores over 2.0 for at least one of the steroid phosphoesters. In contrast, current markers under development for risk of pre-eclampsia have prediction scores ranging from 8 to 33%. As the spiral steroids are lactones, similar to spironolactone and related compounds, they could function as endogenous potassium sparing hormones. However, as only about half of the affected patients had elevated levels of the spiral steroids, it may not be the only underlying pathology. Parturition would end transfer of placental spiral steroids and account for the termination of the symptoms of pre-eclampsia/eclampsia. Previous investigators have proposed inadequate placental function as the critical pathology of pre-eclampsia, but it is hard to imagine how inadequate placental function leads to the maternal pathology without invoking an endogenous potassium sparing hormone originating in the placenta.