Serum Levels of Angiogenic and Antiangiogenic Factors in Ghanaian Women Diagnosed with Pre-Eclampsia and its Relation to Fetal Outcomes

Abstract

Background: Pregnancies complicated by pre-eclampsia are associated with a high rate of maternal and fetal morbidity and mortality. The only effective treatment of pre-eclampsia is premature delivery of the baby and the placenta which can result in neonatal complications. Antiangiogenic and angiogenic factors have been implicated in the pathophysiology of pre-eclampsia resulting in of placental ischemia with subsequent maternal endothelial cell dysfunction and fetal complications. General Aim- The aim of the study was to determine the association between the serum levels of antiangiogenic factor, sFLT-1, angiogenic factor, PLGF and the fetal outcome in pre-eclampsia. Methodology- This study was a case control study which included a total of 120 participants, comprised 60 pre-eclamptic women and 60 pregnant women with no complications. A volume of 6mls of blood was drawn from the antecubital fossa using a 10mls syringe from each participant. This was then divided into two 3mls each, one portion was poured into the plain bottle and the other half into an EDTA tube and labelled with indelible ink appropriately. Blood samples were drawn as follows: at presentation, during the active phase of labour and 24 hours after delivery for each participant. The human soluble fms- like tyrosine kinase 1 and placental growth factor ELISA kit were used to measure the antiangiogenic and angiogenic factors respectively. Full blood count blood, urea, electrolytes, creatinine and uric acid, ALT, AST and albumin were measured. Digital weighing scale was used to measure the weight of each baby and the weight of the placenta. The APGAR scores were calculated at 1 and 5 minutes after delivery. Neonatal admission into NICU and neonatal mortality were recorded. Questionnaires on demographics and knowledge of pre-eclampsia were analyzed. Statistical significance was set at a probability of 0.05

Results- The median serum level of sFLT-1 at diagnosis was significantly higher in women diagnosed with pre-eclampsia compared to controls 49622.6pg/ml (IQR:22256.7-122818.6) versus 14842pg/ml (IQR:6289.0-20607.6) p<0.001. Similarly, the median sFLT-1 level during delivery was 50634.6pg/ml(IQR:24171.1-118934.5) and 25046.6pg/ml (IQR:13570.5-40565.4) p=0.002 while the level 24 hours after delivery was 7521.7pg/ml (IQR: 1321.8-41049.5) and 2477.4pg/ml (IQR: 1038.0-7438.2) p= 0.021 in the case and control respectively. The median serum level of PLGF in women diagnosed with pre-eclampsia was significantly lower than controls,78.7pg/ml (IQR: 46.9-188.7) versus 1016.7pg/ml (IQR:280.7-2177.2), p<0.001. Likewise, the median level of PLGF during delivery was 65.1pg/ml(IQR:41.7-105.3) in cases and 202.6pg/ml(IQR:84.8-418.6) in controls, p<0.001. The median level of PLGF 24 hours after delivery was marginally lower in the case 52.9pg/ml (IQR:20.0-114.3) as compared to the control 58.7pg/ml(IQR:30.75-127.1) p= 0.386. The increased serum levels of the anti-angiogenic sFLT-1 and low serum level of angiogenic factor, PLGF was associated with NICU admissions, neonatal death and low birth weight. However, mothers who had still birth had a low sFLT-1 (p=0.403) and PLGF levels (p=0.736). Conclusion- A high serum sFLT-1 and low PLGF levels in women diagnosed with pre-eclampsia is associated with greater NICU admissions, low birth weight and neonatal death. Furthermore, low sFLT-1 levels after high levels in utero regardless of the PLGF level is associated with still birth in women diagnosed with pre-eclampsia. Therefore, neonatal outcomes may improve if there is regular clinical monitoring of sFLT-1 and PLGF levels for women with pre-eclampsia.