Maternal Serum Soluble Fms- Like Tyrosine Kinase-1 and Placental Growth Factor Ratio as A Short Term Predictor of Pre-Eclampsia

Author(s): Dr. Jesika Rizvi Tamanna, Dr. Mousumi Saha, Dr. khadiza Begum, Dr. Md. Mizanur Rahman, Prof. Dr. Nahreen Akthar, Dr. Abeda Sultana, Prof. Dr. Tabassum Parveen

Background:

Preeclampsia (PE) is defined as new onset of HTN (BP≥ 140/90 mm of Hg on two occasions at least 4 hours apart) after 20 weeks of pregnancy and the coexistence of 1 or more of the following new onset conditions: Proteinuria (Protein creatinine ratio of 30 mg/mmol or Albumin creatinine ratio of 8 mg/mmol or at least 1 gm/L[2+] in dip stick) or other maternal organ dysfunction as renal insufficiency, liver involvement, neurological complications, hematological complications and uteroplacental dysfunction. It is an important cause of maternal & perinatal morbidity and mortality globally. It complicates 10-17% of pregnancy particularly in developing countries. Eclampsia causes 20% of maternal death in Bangladesh. Several predictive markers for pre-eclampsia, including placental growth factor, sFlt-1, Plasma protein 13 and Pregnancy-Associated PAPP-A have been evaluated. The imbalance between angiogenic factors like vascular endothelial growth factor or PLG and anti-angiogenic factors like sFlt-1 are known to be related to the disease pathogenesis. In women with PE, sFlt-1 rises approximately 5 weeks prior to disease onset while the level of PLGF decreases before the rising of sFlt-1. Hence, to improve the quality of PE prediction, some studies suggest sFlt-1/PLGF ratio as a better marker compared to measuring sFlt-1 or PLGF separately as predictor of PE. An elevated ratio is highly predictive of PE within 4 weeks, whereas the diagnosis of PE can be ruled out within one week for low ratios.

Objective:

To evaluate sFlt-1/PLGF ratio in maternal serum between 24+0-36+6 gestation weeks as a short term predictor of preeclampsia.

Methodology:

A longitudinal study was conducted in the Outpatient Department of Fetomaternal Medicine and General Obstetrics and Gynecology, BSMMU, Dhaka. Purposive or convenient sampling technique was applied for data collection. According to inclusion criteria 86 pregnant women between 24+0-36+6 weeks' gestation with at least one risk factor for pre-eclampsia were selected from OPD of Fetomaternal Medicine and General Obstetrics and Gynecology department. The purpose and procedure was discussed and after obtaining informed consent, the women were interviewed. After that 5 ml of blood sample was collected by venipuncture from ante cubital vein and taken in a sterile vacuum container and sent to Virology laboratory of BSMMU. Blood was allowed to cool in room temperature, then serum was separated by centrifugation and stored at -200C until analysis. sFlt-1 and PLGF concentrations were measured by ELISA kit. All participants were invited to follow up at 1 week and 4 weeks of enrollment. At each visit they were clinically evaluated by measuring BP and dipstick test for protein if BP raised. Quantification of proteinuria was done by measuring protein creatinine ratio. Patients who developed pre-eclampsia were recorded as pre-eclampsia group (Group 1) & others were labeled as non-pre-eclampsia group (Group 2). Cut off value of sFlt-1/PLGF ratio was determined for developing PE. Data were analyzed using SPSS software. Area Under ROC was used to find the predictive values of sFlt-1 and PLGF ratio.

Result:

Out of total 86 patients 8(9.30 %) patients developed PE. The both groups were almost similar in terms of all baseline demographic and obstetric characteristics except maternal age and BMI which were significantly higher in PE group (Group 1) than that in non PE group (Group 2). The mean age of PE and non PE patients were 27 years and 24.60 years respectively. The mean of sFlt-1 and PLGF ratio were significantly higher in PE group than in non PE group. Multivariate logistic regression analysis demonstrated that a subject with higher sFlt-1/PLGF ratio had OR 1.675(95.0% CI 0.987-1.315) times increase were significantly associated with short term predictor of PE. In ROC the best combination of sensitivity and specificity for prediction of PE which gave 37.8 cut off value of sFlt-1 and PLGF ratio with 87.50% sensitivity and 92.30 % specificity for short term prediction of pre-eclampsia(PE).

Conclusion:

Our findings revealed that patients who developed pre-eclampsia have high serum level of soluble sFlt-1 and PLGF ratio. sFlt-1 and PLGF ratio below 37.8 can rule out preeclampsia for 4 weeks.