Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana

Abstract

Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study. This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal umbilical artery Doppler impedance indices; resistance index (RI) and systolic diastolic (SD) ratio were determined to confirm utero-placental hypoperfusion. Significantly higher proportions of foeto-maternal complications; eclampsia, low birth weight (LBW), neonatal intensive care unit admissions (NICU), intrauterine growth restriction (IUGR), caesarian deliveries and early gestational age at delivery were associated with PE. Women with PE had lower concentrations of platelet (p = 0.02) whereas red cell distribution width (RDW) was markedly elevated (p = 0.01). NTPro-BNP concentration was markedly elevated (p = 0.01) in women with PE whereas neuropilin-1 concentration was lower (p = 0.03) compared to the non-PE group. Maternal heart rate was elevated in women with PE and Doppler resistance indices (RI and SD) were significantly elevated in foetuses of PE women than foetuses of the controls. Placental mal-perfusion lesions were higher in women with PE compared to the non-PE group. Women with PE had increased risk of adverse foeto-maternal complications, significantly associated with placental mal-perfusion lesions, had reduced platelet concentration and elevated RDW-CV levels. NTPro-BNP, RI and SD are elevated in women with PE whereas neuropilin-1 concentration is reduced. Significant changes in these pathological variables in PE women is indicative of significant derangement in endothelial function culminating in adverse maternal and perinatal outcomes of pregnancy.

Keywords: Eclampsia; NTpro-BNP; Neuropilin-1; Preeclampsia; RI; SD; Serpin E1/PAI-1.

Fig. 1

District map of Ghana showing the three hospitals [10].

Fig. 2

Exclusion variables and sample size justification used in participant selection.

Fig. 3A

Levels of soluble markers of endothelial dysfunction between PE and Non-PE groups. (A) Levels of NT-proBNP between PE and Non-PE. (B) Levels of neuropilin-1 between PE and Non-PE. (C) Levels of serpin E1/PAI-1 between PE and Non-PE. NT-proBNP: N-terminal pro-brain natriuretic peptide, PE: preeclampsia, Non-PE: non-preeclamptic. P-value <0.05 is considered statistically significant different. Fig. 3BLevels of radiological imaging parameters stratified according to PE status. (A) Levels of RI between PE and Non-PE. (B) Levels of SD ratio between PE and Non-PE. (C) Levels of maternal heart rate between PE and Non-PE. RI: resistance index, SD: systolic diastolic, PE: preeclampsia, Non-PE: non-preeclamptic, BPM: beats per minute. P-value <0.05 is considered statistically significant different.

Fig. 3A

Levels of soluble markers of endothelial dysfunction between PE and Non-PE groups. (A) Levels of NT-proBNP between PE and Non-PE. (B) Levels of neuropilin-1 between PE and Non-PE. (C) Levels of serpin E1/PAI-1 between PE and Non-PE. NT-proBNP: N-terminal pro-brain natriuretic peptide, PE: preeclampsia, Non-PE: non-preeclamptic. P-value <0.05 is considered statistically significant different. Fig. 3BLevels of radiological imaging parameters stratified according to PE status. (A) Levels of RI between PE and Non-PE. (B) Levels of SD ratio between PE and Non-PE. (C) Levels of maternal heart rate between PE and Non-PE. RI: resistance index, SD: systolic diastolic, PE: preeclampsia, Non-PE: non-preeclamptic, BPM: beats per minute. P-value <0.05 is considered statistically significant different.

Fig. 4A

Diagnostic performance of soluble markers of endothelial dysfunction in predicting PE beyond the 20th week of gestation. (A) N-terminal pro-brain natriuretic peptide (B) Neuropilin-1.

Fig. 4B

Diagnostic performance of RI and SD ratio in predicting PE beyond the 20th week of gestation. (C) SD ratio: systolic diastolic ratio, (D) RI: resistance index.

Fig. 4C

Diagnostic performance of maternal heart rate in predicting PE beyond the 20th week of gestation. (E) Maternal heart rate.

Fig. 5

Shows umbilical artery Doppler velocity waveform patterns of 4 pregnant women at term. A and B show normal umbilical artery Doppler (normal vessel) pattern, C and D show reduced end-diastolic flow.

Fig. 6A

Shows placental histological lesions (A) Placenta showing normal villi viewed under ×10. (B) 1 and 2 show placental sickling and 3–5 show cytotrophoblastic proliferation viewed under ×10. (C) Infarction viewed under ×10 objective (D) Small sclerotic villi is represented by blue arrows and black arrows represent sickled RBCs viewed under ×40. Fig. 6B: Shows placental histopathological lesions. (E) Villous fibrosis observed under ×10 objective (F) Blue arrows represents syncytial knots whereas the black arrow represents intervillous space hemorrhage made up of normal RBCs and sickled RBCs viewed under ×10 magnification (G) Hypermatured villi viewed under ×40 objective (H) Shows perivillous hyalination represented by blue arrow and intervillous space hemorrhage represented by black arrow viewed under ×40 objective.