Abstract:
Pre-eclampsia (PE) is a disorder that occurs in pregnancy and affects about 7-10% of
all pregnancies. It is characterized by hypertension and proteinuria, and there may be
involvement ofthe central nervous system and the blood or disseminated
intravascular coagulation (DIC). The aim of the study were to determine expression
of Platelet Cell Adhesion Molecule-l (PECAM-l) and E-selectin, Vascular
Endothelial Growth Factor (VEGF) and its receptor (VEGFR-l), endothelial Nitric
Oxide Synthase (eNOS) and Plasminogen Activator Inhibitor 1 (PAl-I) to determine
their role in pathogenesis of PE and eclampsia. The secondary aim was to determine
the risk factors for PE and eclampsia and relate placental histopathological lesions to
clinical findings and neonatal outcome. Other aims included determining changes in
haematological and coagulation indices in PE/eclampsia and evaluate if early
involvement of platelets could be used as a suitable marker for early detection of PE.
METHODOLOGY: Included in the study were 114 pregnant women delivering in
Muhimbili National Hospital between January and December 2001 with a diagnosis
of pre-eclampsia or eclampsia and healthy pregnant women (controls).
Placenta, cord, extraplacental membranes and serum for coagulation indices
determination were collected from these women of which 43 were pre-eclamptic, 31
eclamptic and 40 were healthy pregnant women (controls)
Standardized questionaire designed for this study was used to record maternal and
infant clinical characteristics and placental parameters.
Placenta, cord and membranes which were collected immediately after delivery, fixed
in formalin and paraffin embedded. The sections were stained by Hand E and
examined by light microscopy.Placenta and membrane sections were stained by
immunohistochemistry.
RESULTS: Pre-eclamptics/eclamptis were mostly primigravida and had significantly
lower gestational age and birth weight of infants. Multigravida women with
PE/Eclampsia were more likely to have positive family history or have changed
husbands from the previous pregnancy. Presence of extensive infarction was
significantly associated with low birth weight of the neonate (P< 0.001, OR; 24.22
(95 % Cl: 7.0-83.3).
Immunohistochemical findings: There were no statistical significant differences in
placental expression of PE CAM-l and E-selectin in placenta from PE/eclamptic
patients compared to controls. Significantly strong staining intensity ofVEGF and
VEGFR-l (Flt-l ), e-NOS3 and PAl-l expression in villous syncytiotrophoblasts was
seen in the placenta from pre-eclamptic and eclamptic patients compared to controls.
DISCUSSION: The present study has shown similar risk factors for PE as is reported
in other studies. High expression ofVEGF and VEGFR-l found in patients with
PE/eclampsia implies that blocking ofVEGFR and its receptor can be exploited to
plan for new therapeutic protocols in these conditions. Anti- VEGF are now currently
being used for the treatment of various cancers. The findings in this study can
therefore be used to extend this management to pre-eclamptic/eclamptic patients.
However, this needs pre-clinical and clinical trials to determine efficacy and safety
levels.The increase in VEGFR and its receptor in placenta from pre-eclamptic and
eclamptic patients and colocalization found in this study implies that the association
may have pathogenetic role. Since PAI-l is involved in fibrin deposition and
placental occlusive lesions, its increased expression observed in PE/eclamptic patients
in this study supports a thrombotic role.
CONCLUSIONS: Pre-eclampsia and eclampsia in Muhimbili National Hospital is
associated with multiple risk factors. Over expression ofVEGF and its receptor,
eNOS and PAI-l suggests that these molecules may play a significant role in the
pathogenesis of PE and eclampsia in our patients. These findings may be important in
the formulation of new therapeutic approaches to treatment of PE and eclampsia.
Health education to all women to avoid change of husbands may help in the
prevention of pre-eclampsia. Strategies which target VEGF/ VEGFR-l pathway may
halt progression of PE/eclampsia.
RECOMMENDATIONS: Administration of anti-thrombotic agents such as low
molecular weight heparin or low dose aspirin to at risk patients for PE/eclampsia may
improve pregnancy outcome in these patients. The use of vasodilators to improve the
vascular tone in patients with PE/eclampsia should be explored. Further pre-clinical
and clinical studies are needed to further elucidate the pathogenesis of preeclampsia
and eclampsia and the usefulness of targeting VEGFNEGFR-l pathway in the
management.