We read with great interest the report on preeclampsia (PE), biomarkers, syncytiotrophoblast (STB) stress, and placental capacity by Redman and Staff. The authors effectively elaborate 2 stages of PE progression, ie: poor placentation and subsequent maternal systemic inflammatory response.

PE is an obstetric disorder that has perplexed clinicians for decades due to its unknown underlying mechanism. The authors, however, tried to simplify the pathophysiology of PE by explaining the role of STB and placental stress. One of the highlights of this report is the proposition that PE research should be focused on STB stress rather than circulating biomarkers, as these arise due to STB stress and the consequence of which is PE. But the STB cellular response can be measured only by estimation of circulating levels of biomarkers such as placental growth factor and soluble fms-like tyrosine kinase-1. Therefore, robust placental markers should be identified that will delineate onset of STB cellular stress. Apart from STB stress, elucidation of mechanisms involved in trophoblast invasion and uterine artery remodeling should be the prime focus. Even though STB cellular stress can unravel certain aspects of PE, it cannot differentiate between late-onset PE and post-term pregnancy. One of the widely proposed explanations for PE onset is failure of vascular remodeling of uterine artery. Future research should be focused on identification of factors that trigger abnormal remodeling of uterine spiral arteries. Similarly, it is well known that vascular mimicry involved in remodeling of uterine arteries gets completed in pregnancy at term, but what expedites this process in PE should be unraveled by extensive research.

Another important aspect of PE physiology is differential response pattern to inadequate trophoblast invasion and vascular remodeling in pregnant women. In a few women, the impaired trophoblast invasion leads to PE, while in a few others, it results in intrauterine growth restriction or preterm delivery. Hence in combination with placental factors, the role of maternal and metabolic factors should be evaluated, in context to the onset of PE. Overall, the authors convincingly explained the importance of STB cellular stress and stress response in terms of associated markers in onset of PE, but until fine intricacies of normal pregnancy such as placentation and immune tolerance are completely delineated, understanding of PE pathophysiology will remain a distant goal.