Preeclampsia

Although the cause of preeclampsia remains unclear, the syndrome may be initiated by an imbalance of placental factors that induce endothelial dysfunction. sFlt-1 (soluble fms-like tyrosine kinase 1) and PIGF (placental growth factor) are both associated with placental dysfunction and risk of PE during pregnancy. Women with PE have been reported to have increased circulating concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1), an antiangiogenic protein largely produced in the placenta, which is associated with inhibition of vascular endothelial growth factor and placental growth factor (PlGF). During pregnancy, PlGF concentrations typically increase progressively in the first and second trimesters and then decrease toward full term. In contrast, in cases of clinical preeclampsia, sFlt-1 concentrations are significantly increased versus concentrations observed in normal pregnancies, while concentrations of circulating free PlGF are significantly decreased relative to normal pregnancy.

The use of the sFlt-1/PIGF ratio has been shown to be a useful tool to aid in risk assessment of patients with clinical signs and symptoms consistent with the development of preeclampsia with severe features (as defined by the American College of Obstetricians and Gynecologists [ACOG, 2020] guidelines). Based on the data collected during the PRAECIS clinical study, the prognostic performance of the sFlt-1/PIGF ratio using a ratio cutoff of 40 (where if the ratio is greater than or equal to 40, there is a high risk for progression to preeclampsia with severe features), exhibited a sensitivity of 94% and specificity of 75% for the development of PE with severe features within two weeks. The performance of the sFlt-1/PlGF ratio to predict the development of PE with severe features within two weeks was statistically higher than the prognostic performance of other commonly used clinical (highest systolic blood pressure (SBP), highest Diastolic blood pressure (DBP) and laboratory general markers associated with preeclampsia such as AST, ALT, creatinine, and platelets).

New targeted prognostic assays for preeclampsia risk assessment are an important first step toward improving overall maternal health. The comprehensive clinical research behind the new test sets the stage for the use of more biomarkers to assess patient risk, inform care decisions, and improve maternal and fetal outcomes globally.

Key testing

• PERA | Preeclampsia sFlt-1/PIGF (Soluble fms-Like Tyrosine Kinase 1/ Placental Growth Factor) Ratio, Serum
  • Aids in risk assessment of patients with clinical signs and symptoms consistent with preeclampsia for the development of preeclampsia with severe features.
  • Indicated for use in pregnant women, with singleton pregnancies (gestational age 23 to 34+6/7 weeks) hospitalized for hypertensive disorders of pregnancy (preeclampsia, chronic hypertension with or without superimposed preeclampsia, or gestational hypertension) within two weeks of presentation.
  • A sFlt-1/PlGF ratio ≥40 suggests the pregnant woman is at high risk for progression to preeclampsia with severe features within two weeks of presentation.
  • A sFlt-1/PlGF ratio <40 suggests the pregnant woman is at low risk for progression to preeclampsia with severe features within two weeks of presentation.

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References

1. Centers for Disease Control and Prevention. (2023, June 19). High blood pressure during pregnancy. https://www.cdc.gov/bloodpressure/pregnancy.htm
2. Khan, R. (2023, Nov. 29). Contributor: more informed management of preeclampsia is necessary. The American Journal of Managed Care. https://www.ajmc.com/view/contributor-more-informed-management-of-preeclampsia-is-necessary
3. Thermo Fisher Scientific. (n.d.) Insights on preeclampsia management. Accessed Jan. 24, 2024. https://www.thermofisher.com/procalcitonin/us/en/preeclampsia-fda.html