Poster Presentation - SOMANZ ASM Society of Obstetric Medicine of Australia and New Zealand ASM 2023

An evaluation of the sFlt-1/PlGF ratio in preeclampsia and gestational diabetes mellitus (#63)

Sarah B Noonan 1 , Gabriel D Jones 2 , Shaun P Brennecke 3 4
  1. Melbourne Medical School, The University of Melborune, Melbourne, Victoria, Australia
  2. Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK
  3. Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women’s Hospital, Melbourne, Victoria, Australia
  4. Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia

Background

An imbalance between anti-angiogenic and pro-angiogenic factors plays a role in the development of preeclampsia (PE). The ratio between two such markers, soluble fms-like tyrosine kinase 1 (sFlt-1; anti-angiogenic) and placental growth factor (PlGF; pro-angiogenic), can be utilised to predict a subsequent diagnosis of PE up to four weeks in advance (Zeisler et al., 2016). Gestational diabetes mellitus (GDM) is associated with changes in angiogenic biomarkers (Nuzzo et al., 2021). However, there is an incomplete understanding of whether GDM has an influence on sFlt-1 or PlGF, and how this may affect the accuracy of predicting PE onset with the sFlt-1/PlGF ratio.

Aim

To investigate whether there is a significant difference in the sFlt-1/PlGF ratio in individuals with PE and GDM compared to those with PE and no GDM.

Method

A retrospective analysis of 3,841 sFlt-1, PlGF and sFlt-1/PlGF biomarker ratio measurements was performed on data acquired between September 2016 and September 2022 at the Royal Women’s Hospital, Melbourne. Exclusion criteria included: multiple biomarker tests, pre-existing diabetes, renal disease, anti-phospholipid syndrome, systemic lupus erythematosus, fetal chromosomal abnormalities, multiple pregnancy, and pregnancy induced hypertension. 1,416 biomarker ratio measurements remained for analysis. Cases were partitioned into four groups: GDM + PE, GDM + No PE, No GDM + PE and No GDM + No PE. The sFlt-1/PlGF ratio was compared between GDM + PE and No GDM + PE cases at 28 days, 14 days, and 7 days before delivery.

Results

At 7 days before delivery, the median sFlt-1/PlGF ratio was 28.0 (IQR, 13.0 – 55.25) in No GDM + No PE groups, 90.0 (IQR, 49.0 – 180.0) in No GDM + PE groups, 17.0 (IQR, 8.75 – 31.5) in GDM + No PE groups and 135.0 (IQR, 66.0 – 315.0) in GDM + PE groups. As expected, PE pregnancies had a significantly higher median sFlt-1/PlGF ratio than no PE pregnancies (Mann-Whitney test, p<0.001). Of note, GDM + PE pregnancies had a significantly higher median sFlt-1/PlGF ratio than No GDM + PE pregnancies (Mann-Whitney, p = 0.025). A similar trend of sFlt-1/PlGF values was also observed across all four groups at 14 and 28 days before delivery.

Conclusion

These results indicate a potential need to consider GDM status when interpreting sFlt-1 and PlGF biomarker values when ruling in or out a diagnosis of PE, and suggest current cut-off values may need to be re-evaluated for use in this patient population.

 

  1. Nuzzo, A.M., et al., Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus. Sci Rep, 2021. 11(1): p. 2312.
  2. Zeisler, H., et al., Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med, 2016. 374(1): p. 13-22.