Identification of Novel Syncytiotrophoblast Membrane Extracellular Vesicles Derived Protein Biomarkers in Preeclampsia: A Cross-Sectional Study

Reviewer #1 (Public Review):

The authors primary objective in this study was to identify differences between patients with preeclampsia and normal patients with respect to the placental syncytiotrophoblast extracellular vesicle proteome.

One of the strengths of this study is that it is one of only a few studies that investigated the difference in proteome between patients with preeclampsia and those with normal pregnancies using placental extracellular vesicles obtained by an ex-vivo dual lobe placenta perfusion technique.

The main weaknesses of this study are:

1. The small sample size in that there were only 12 cases.
2. The study patients and control population of normal pregnancies were not matched for gestational age at delivery.

The authors were able to achieve their study aims and the results support their conclusions.

These findings could be used in future studies of the disease mechanisms and as biomarkers for prediction of preeclampsia. As such, they may be very useful for the identification of women at risk for preeclampsia well before the onset of disease.

Reviewer #2 (Public Review):

Summary:

Preeclampsia is a disorder of pregnancy that affects 4-5% of pregnancies worldwide. Identifying this condition early is clinically relevant as it will help clinicians to make management decisions to prevent adverse outcomes. The placenta holds a key to many pregnancy-related pathologies including preeclampsia and studies have shown many differences in the placenta of women with preeclampsia as compared to controls. However as the placenta cannot be collected directly during pregnancy, the exosomes secreted by it are considered a good alternative to tissue biopsy. In this study, the authors have compared the proteins in different sizes of exosomes from the placenta of women with and without preeclampsia. The idea is to eventually use these as biomarkers for early detection of preeclampsia.

Strengths:

The novelty factor of this study is the use of two different-sized exosomes which has not been achieved earlier.

Weaknesses:

There is already enough information about the differences in exosome contents from the placentas of women with and without preeclampsia. There are some issues with the methods which may influence the outcomes of the data.

The patient population described in the methods section is of HELLP syndrome while the title and the manuscript describe preeclampsia. While it is an important life-threatening condition to address, it is extremely rare and needs careful assessment by clinicians in terms of patient characteristics and outcomes measured.

The study measured the proteins at only a single time point after the disease has already occurred. However, the placenta is an ever-changing tissue throughout pregnancy and different proteins can come up at different times in pregnancy. Thus serial measurements are necessary and a single time point measurement like that done here does little value addition. Unfortunately, this site has not validated the identified biomarkers in plasma or circulating placental exosomes from women with and without preeclampsia. Thus the validity of these findings in real-life situations can not be judged.