The feasibility of soluble Fms-Like Tyrosine kinase-1 (sFLT-1) and Placental Growth Factor (PlGF) ratio biomarker in predicting preeclampsia and adverse pregnancy outcomes among medium to high risk mothers in Kuala Lumpur, Malaysia

Abstract

Background Preeclampsia significantly contributes to maternal and perinatal morbidity and mortality. It is imperative to identify women at risk of developing preeclampsia in the effort to prevent adverse pregnancy outcomes through early intervention. Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) level changes are noticeable several weeks before the onset of preeclampsia and its related complications. This study evaluated the feasibility of the sFlt-1/PlGF biomarker ratio in predicting preeclampsia and adverse pregnancy outcomes using a single cut-off point of >38. Methods This is a prospective cohort study conducted at a single tertiary centre, in an urban setting in Kuala Lumpur, Malaysia, between December 2019 and April 2021. A total of 140 medium to high risk mothers with singleton pregnancies were recruited at ≥20 weeks’ gestation. sFlt-1/PlGF ratio was measured and the participant monitored according to a research algorithm until delivery. The primary outcome measure was incidence of preeclampsia and the secondary outcome measure was incidence of other adverse pregnancy outcomes. Results The overall incidence of preeclampsia was 20.7% (29/140). The mean sFlt-1/PlGF ratio was significantly higher in preeclampsia (73.58 ± 93.49) compared to no preeclampsia (13.41 ± 21.63) (p = 0.002). The risk of preeclampsia (adjusted OR 28.996; 95% CI 7.920–106.164; p<0.001) and low Apgar score (adjusted OR 17.387; 95% CI 3.069–98.517; p = 0.028) were significantly higher among women with sFlt-1/PlGF ratio >38 compared with sFLT-1/PlGF ratio ≤38. The area under the receiver-operator characteristic curve (AUC) for a combined approach (maternal clinical characteristics and biomarker) was 86.9% (p<0.001, 95% CI 78.7–95.0) compared with AUC biomarker alone, which was 74.8% (p<0.001, 95% CI 63.3–86.3) in predicting preeclampsia. The test sensitivity(SEN) was 58.6%, specificity (SPEC) 91%,positive predictive value (PPV) 63% and negative predictive value (NPV) 89.3% for prediction of preeclampsia. For predicting a low Apgar score at 5 minutes, the SEN was 84.6%, SPEC 87.4%, PPV 40.7%, and NPV 98.2%; low birth weight with SEN 52.6%,SPEC 86.0%, PPV 37.0%, NPV 92.0%; premature delivery with SEN 48.5%, SPEC 89.5%, PPV 59.3%, NPV 84.7% and NICU admission with SEN 50.0%, SPEC 85.8%, PPV 37.0% and NPV 91.2%. Conclusions It is feasible to use single cut-off point of >38 ratio of the biomarkers sFlt-1/PlGF in combination with other parameters (maternal clinical characteristics) in predicting preeclampsia and adverse pregnancy outcomes among medium to high risk mothers without restricting outcome measurement period to 1 and 4 weeks in a single urban tertiary centre in Kuala Lumpur, Malaysia.

The Role of Biochemical Markers in the Prediction of Preeclampsia

“…The placental growth factor (PlGF) is a proangiogenic factor that is produced in the placenta. It improves the action of vascular endothelial growth factor-A (VEGF-A), which is essential for vascular homeostasis [32,33]. PIGF can be measured in the maternal blood from the 8th week of gestation; then it is reduced progressively after the second trimester of pregnancy, until delivery.…”

“…PIGF can be measured in the maternal blood from the 8th week of gestation; then it is reduced progressively after the second trimester of pregnancy, until delivery. However, PlGF remains persistently low in preeclampsia due to the increased levels of soluble Feline McDonough Sarcoma fms-like tyrosine kinase-1 (sFlt-1) [33][34][35]. The sFlt-1 is an anti-angiogenic factor that increases significantly in the maternal circulation through normal pregnancy, yet it increases even more in preeclampsia [36].…”