Background: Preeclampsia (PE) is a multisystem disorder, usually defined as the development of hypertension and proteinuria after 20 weeks of pregnancy. The sFlt-1/PlGF ratio has been widely studied as a diagnostic and prognostic marker of preeclampsia and other manifestations of placental dysfunction. A sFlt-1/PlGF ratio greater than 85 for early PE, less than 34 weeks of gestation suggests a high risk of PE requiring close clinical monitoring.
Objective: To evaluate the maternal and perinatal outcomes of pregnancies with an extremely high sFlt-1/PlGF ratio.
Case Presentation: The analysis included data on placental growth factor and soluble fms-like tyrosine kinase serum levels, measured during 2017-2020 in 128 pregnant women. Here we present 8 cases of women with a numerical ratio greater than 850.
In all 100% of cases, the signs of obstetric angiogenic catastrophe requiring imminent delivery developed soon.
Conclusion: We observed a trend for worsening perinatal outcomes in women with an extremely high sFlt-1/PlGF of ≥850.
Placental Dysfunction; Preeclampsia; sFlt/PIGF Ratio
Pregnancy becomes a life-threatening condition for 10 million women annually. The most common complication is preeclampsia, which complicates 5 to 10% of pregnancies in the United States and up to 18% in some regions of Africa .
Preeclampsia is the leading cause of death for young women, particularly those living in resource-limited settings, and it leads to approx. 76,000 maternal deaths and 500,000 infant deaths worldwide each year .
Preeclampsia (PE) is a multisystem disorder, usually defined as the development of hypertension and proteinuria after 20 weeks of pregnancy . Recent PE pathophysiology studies open up interesting prospects for screening for this disease.
As a sign of placental dysfunction, preeclampsia is associated with dysregulation of pro- and antiangiogenic factors . Although the etiology of PE has not been fully understood, it is believed to occur due to impaired placentation in early pregnancy. Defective trophoblast invasion and abnormal remodeling of spiral arteries result in placental hypoperfusion and, as a consequence, leads to oxidative stress . Therefore, placenta releases a large number of antiangiogenic factors into the maternal circulation [5-7]. During normal pregnancy, concentrations of antiangiogenic factor sFlt-1 (soluble fms-like tyrosine kinase-1) remains low, allowing accurate transmission of signals induced by proangiogenic factors such as VEGF (vascular endothelial growth factor) and PlGF (placental growth factor). This balance is crucial to maintain physiological vasodilation . Secondary to hypoperfusion, placenta increases the synthesis of sFlt-1, trying to raise maternal blood pressure and increase placental perfusion. Consequently, levels of circulating proangiogenic factors are reduced and vascular homeostasis is altered, causing endothelial dysfunction, which leads to hypertension, proteinuria and other multiorgan manifestations of PE in mother .
Measurements of blood pressure and proteinuria are considered the gold standard for the diagnosis of preeclampsia, although they do not predict the adverse perinatal outcomes with adequate accuracy . Clinically, hypertension and proteinuria do not always reflect the severity of the disease.
The sFlt-1/PlGF ratio has been widely studied since 2004 as a diagnostic and prognostic marker of preeclampsia and other manifestations of placental dysfunction . To date, a large prospective clinical trial PROGNOSIS has clearly demonstrated that the sFlt-1/PlGF ratio ≤38 may be used to rule out PE within one week, independently of gestational age . A sFlt-1/PlGF ratio greater than 85 (for early PE, Thus, estimated sFlt-1/PlGF ratio can be of great added value when used as an add-on to routine assessment methods. Accurate prediction of PE is important, since severe symptoms may worsen both maternal and fetal status.
The main objective of the expectant management of PE is to improve perinatal outcomes owing to delayed delivery, thereby reducing neonatal morbidity and mortality. In 2012, Verlohren S, et al. (2014) , reported that a sFlt-1/PlGF ratio above 655 identified women at high risk of imminent preterm delivery before 34 weeks of gestation, who therefore required close monitoring and medical care.
However, in a study by Stolz M, et al. (2018) , a sFlt-1/PlGF ratio above 655 did not predict worsening of perinatal outcomes and was not reliable enough to predict results in cases with clinical signs of PE. Nevertheless, the data obtained suggest that an extremely high sFlt-1/ PlGF ratio greater than 850 may be more helpful.