Preeclampsia is a serious hypertensive condition that affects 3.4% of pregnant individuals in the United States. It is responsible for 14% of deaths in pregnant patients and between 10 and 25% of perinatal deaths.
Patients typically develop hypertension after 20 weeks of gestation. Preeclampsia can range from mild to severe. The severe form occurs in about 20% of affected women and may require premature delivery.
Preeclampsia is thought to be caused by improper development of the placenta due to an imbalance of placental factors that regulate endothelial function. Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) have both been associated with placental dysfunction and the risk of developing preeclampsia during pregnancy.
Normally, PlGF concentrations increase during the first and second trimester and then decrease by the end of the third trimester. sFlt-1 is an anti-antiogenic protein produced by the placenta that inhibits vascular endothelial growth factor and PlGF. In preeclampsia, sFlt-1 concentrations are significantly increased, while concentrations of PlGF are decreased.
Measurement of the sFlt-1/PlGF ratio is useful in assessing the risk of development of severe preeclampsia in patients presenting with clinical signs and symptoms of preeclampsia, as defined by American College of Obstetricians and Gynecologists guidelines.
The PRAECIS clinical study determined that a sFlt-1/PIGF ratio of 40 or higher could be used to predict the development of severe preeclampsia within 2 weeks. The sensitivity was 94% and specificity was 75%. The performance of sFlt-1/PlGF was better than other commonly used clinical and laboratory parameters such as blood pressure and aspartate aminotransferase, alanine aminotransferase, creatinine, and platelet count.
In June 2024, ACOG released a new clinical practice update on how to use the sFlt-1:PlGF ratio for preeclampsia. The ratio is intended to assess the risk of preeclampsia in pregnant patients between 23 and 34 weeks gestation with clinical signs and symptoms of a hypertensive disorder.
Reference value is a sFlt-1/PlGF ratio of less than 40. A higher value indicates a pregnant individual is at high risk for progression to preeclampsia with severe features within 2 weeks of presentation. A ratio less than 40, indicates the individual is at low risk of progressing to severe preeclampsia within the next 2 weeks. Patients with a positive result should be monitored closely, while those with a negative result can be managed expectantly.
The sFlt-1/PlGF ratio has been widely used in the UK and Europe for years. Thermo Fisher received FDA approval for its BRAHMS KRYPTOR assays of sFlt-1 and PlGF in 2023. These are homogeneous sandwich immunoassays for the measurement of sFlt-1 and PIGF in human serum.
Specimen is a red top tube blood.
References
Dathan-Stumpf A, Rieger A, Verlohren S, Wolf C, Stepan H. sFlt-1/PlGF ratio for prediction of preeclampsia in clinical routine: A pragmatic real-world analysis of healthcare resource utilisation. PLoS One. 2022;17(2):e0263443. Published 2022 Feb 24. doi:10.1371/journal.pone.0263443
Zeisler H, Llurba E, Chantraine F, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016;374(1):13-22. doi:10.1056/NEJMoa1414838
Thadhani R, Lemoine E, Rana S, et al. Circulating angiogenic factor levels in hypertensive disorders of pregnancy. NEJM. 2022;1(12). doi:10.1056/EVIDoa2200161
Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gyneco. 2020;135(6):e237-e260
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