PlGF (placental growth factor) based testing to help diagnose suspected pre-eclampsia (preeclampsia)

Last edited 03/2022 and last reviewed 03/2022

Placental growth factor (PlGF)-based tests are intended to be used with clinical judgement and other diagnostic tests, to help diagnose suspected pre-eclampsia

  • assessment focuses on diagnosing pre-eclampsia in the second and third trimesters of pregnancy
  • using PlGF-based tests in addition to standard clinical assessment could result in a faster and more accurate diagnosis of pre-eclampsia, and better risk assessment for adverse outcomes in women with suspected pre-eclampsia.
  • could also allow women in whom pre-eclampsia has been ruled out with a PlGF-based test to return to community care instead of being admitted to hospital for observation (1)

PlGF-based tests measure the amount of PlGF in blood plasma or serum

  • PlGF is a protein involved in placental angiogenesis (the development of new blood vessels)
  • in pre-eclampsia, levels of PlGF can be abnormally low
  • in normal pregnancy, PlGF levels rise and peak at 26-30 weeks, so when PlGF levels do not rise during pregnancy there may be placental dysfunction

In addition, some PlGF-based tests measure soluble FMS-like tyrosine kinase-1 (sFlt-1), a protein that is thought to disable other proteins associated with blood vessel formation, such as PlGF

  • in women who develop pre-eclampsia, the levels of sFlt-1 are higher than those seen in normal pregnancy

NICE guidance states (1):

  • the Triage PlGF test and the Elecsys immunoassay sFlt-1/PlGF ratio, used with standard clinical assessment and subsequent clinical follow-up, are recommended to help rule-out pre-eclampsia in women presenting with suspected pre-eclampsia between 20 weeks and 34 weeks plus 6 days of gestation
  • when pre-eclampsia is not ruled-out using a PlGF-based test result, the result should not be used to diagnose (rule-in) pre-eclampsia

Notes (2):

  • placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family and is predominantly expressed in the placenta, although it is also expressed at low levels in many other tissues, including the heart, lung, thyroid, liver, skeletal muscle and bone
    • human PlGF gene is located on chromosome 14q14 and encodes 4 isoforms of PlGF
    • placental growth factor binds to VEGFR-1 (vascular endothelial growth factor-1 receptor-1) or FLT-1 (fms-related tyrosine kinase-1) and its soluble variant sFLT-1 (soluble fms-like tyrosine kinase-1)
  • serum and urinary PlGF is found to be decreased in women both at the time of diagnosis with pre-eclampsia and well in advance of syndrome onset
    • deficiency in PlGF is likely due to a combination of decreased expression of PlGF and reduced free PlGF due to binding with sFLT-1, which is elevated in affected women
    • in early pregnancy, PlGF concentrations are lower in women who subsequently develop preclampsia than in normal pregnant women, but sFLT-1 levels are no different, suggesting that PlGF expression in the placenta is decreased
    • towards completion of pregnancy, there is a reciprocal relationship between sFLT-1 and PlGF with rising levels of total (free and bound to VEGF or PlGF) sFLT-1 and lower free PlGF levels
      • suggests that in the latter half of pregnancy, low PlGF concentrations occur predominantly due to sequestering of PlGF by sFLT-1
      • low circulating PlGF is probably both a consequence of abnormal early events in placentation and a contributing factor to continued abnormal growth during the latter half of pregnancy
        • hypothesis that PlGF is an indicator of abnormal placentation is supported by the observation that women without pre-eclampsia who give birth to small for gestational age babies also have low PlGF early in pregnancy