Preeclampsia and eclampsia are serious hypertensive complications of pregnancy and remain significant contributors to maternal and perinatal morbidity and mortality, particularly in developing countries (1). Preeclampsia is clinically defined by new-onset hypertension after 20 weeks of gestation accompanied by proteinuria or other systemic disturbances, whereas eclampsia is characterized by the onset of seizures in a preeclamptic patient in the absence of other neurologic conditions (2). Despite extensive research, the exact pathogenesis of these conditions remains incompletely understood, though placental dysfunction plays a pivotal role in their development (3).

The placenta in hypertensive disorders of pregnancy frequently exhibits pathological changes indicative of abnormal placentation and compromised uteroplacental perfusion. Histological findings such as increased syncytial knots, villous infarctions, fibrinoid necrosis, and accelerated villous maturation are commonly reported (4,5). These features are considered a reflection of chronic placental ischemia, which is thought to result from deficient trophoblastic invasion and inadequate remodeling of the spiral arteries (6).

Moreover, several angiogenic and anti-angiogenic biomarkers have been implicated in the pathophysiology of preeclampsia and eclampsia. Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are pro-angiogenic factors essential for placental vascular development, while soluble fms-like tyrosine kinase-1 (sFlt-1) acts as an anti-angiogenic factor by binding and neutralizing VEGF and PlGF (7). An imbalance between these factors, particularly elevated levels of sFlt-1 and decreased levels of VEGF and PlGF, has been observed in women with preeclampsia and is even more pronounced in those with eclampsia (8,9).

Given the clinical importance of early detection and differentiation of these conditions, studying the histomorphological alterations alongside biomarker expression patterns may offer insights into disease severity and pathogenesis. This study aims to compare the placental histopathological features and biomarker profiles in women diagnosed with preeclampsia and eclampsia to better understand the underlying pathology and guide potential diagnostic advancements.

A total of 60 placental samples were included, collected from women diagnosed with hypertensive disorders of pregnancy post-delivery. The participants were divided into two groups: Group A (n=30) with clinically confirmed preeclampsia and Group B (n=30) with eclampsia. Inclusion criteria included singleton pregnancies beyond 28 weeks of gestation, with confirmed diagnosis based on blood pressure records and relevant clinical features. Cases with coexisting gestational diabetes, intrauterine infections, or congenital fetal anomalies were excluded.

Sample Collection and Gross Examination:

Immediately after delivery, placentas were washed with normal saline and examined grossly for weight, shape, infarcts, hematomas, and cord insertion. Sections were obtained from standardized sites including the central and peripheral regions, maternal surface, and any visible lesions.

Histopathological Analysis:

Tissue samples were fixed in 10% buffered formalin, processed routinely, embedded in paraffin, sectioned at 4–5 µm thickness, and stained with hematoxylin and eosin. Microscopic evaluation focused on syncytial knots, villous infarction, fibrinoid necrosis, stromal fibrosis, and villous maturation. All slides were examined independently by two experienced pathologists blinded to the clinical diagnosis.

Immunohistochemical (IHC) Evaluation:

Selected paraffin blocks were subjected to immunohistochemistry for VEGF, PlGF, and sFlt-1 using commercially available monoclonal antibodies (Manufacturer: [Insert Company]). The antigen retrieval was carried out in citrate buffer (pH 6.0) using a microwave technique. Diaminobenzidine was used as chromogen, and slides were counterstained with hematoxylin. Staining intensity and percentage of positive villous cytotrophoblast and syncytiotrophoblast cells were evaluated using a semi-quantitative H-score method.

Statistical Analysis:

Data were compiled and analyzed using SPSS version 26.0 (IBM Corp., USA). Categorical variables were expressed as percentages and compared using the Chi-square test. Quantitative data were presented as mean ± standard deviation (SD) and compared using the independent samples t-test. A p-value of <0.05 was considered statistically significant.

A total of 60 placental samples were analyzed, comprising 30 cases of preeclampsia and 30 cases of eclampsia. The mean maternal age was 27.3 ± 3.8 years in the preeclampsia group and 26.8 ± 4.2 years in the eclampsia group, with no statistically significant difference (p = 0.56).

Gross Placental Findings

On gross examination, placental weight was significantly reduced in eclampsia cases (mean: 410.2 ± 52.7 g) compared to preeclampsia cases (mean: 458.6 ± 49.3 g) (p = 0.003). Placental infarctions were more commonly observed in eclampsia (83.3%) than in preeclampsia (60.0%) (Table 1). Marginal cord insertion was more frequent in eclampsia (26.7%) than in preeclampsia (13.3%).

Table 1: Comparison of Gross Placental Features Between Preeclampsia and Eclampsia Groups

Infarcts were significantly more prevalent in the eclampsia group (Table 1).

Histopathological Findings

Microscopic examination showed a higher frequency of pathological changes in the eclampsia group. Increased syncytial knots were seen in 70.0% of eclampsia samples versus 46.7% in preeclampsia. Villous infarction and fibrinoid necrosis were more frequent in eclampsia (Table 2). Accelerated villous maturation was observed in 80.0% of eclampsia samples compared to 53.3% of preeclampsia cases (p = 0.02).

Table 2: Histopathological Changes in Placental Samples

Histological abnormalities were significantly more pronounced in the eclampsia group (Table 2).

Immunohistochemical Analysis

The expression levels of VEGF and PlGF were significantly reduced in the eclampsia group, while sFlt-1 levels were elevated. The mean H-score for VEGF was 65.2 ± 10.5 in preeclampsia and 48.7 ± 8.9 in eclampsia. For sFlt-1, the H-scores were 128.4 ± 12.3 (preeclampsia) and 143.6 ± 11.7 (eclampsia), indicating a statistically significant increase (p < 0.001) (Table 3).

Table 3: Biomarker Expression Scores in Placental Tissue

Immunohistochemistry revealed a significant angiogenic imbalance, particularly in the eclampsia group (Table 3).

This study evaluated and compared the placental histomorphological changes and angiogenic biomarker expression in cases of preeclampsia and eclampsia. The findings support the hypothesis that placental dysfunction is more profound in eclampsia and is reflected both microscopically and biochemically.

The reduced placental weight observed in eclampsia is consistent with previous reports indicating impaired trophoblastic invasion and decreased uteroplacental perfusion in hypertensive pregnancies (1,2). A smaller placenta often reflects chronic hypoxia, which can result in intrauterine growth restriction and adverse neonatal outcomes (3).

Placental infarctions were significantly more frequent in the eclampsia group in this study. These infarcts result from occlusion of maternal spiral arteries and represent areas of necrotic villi due to ischemia (4). Similar findings have been reported in other histological studies comparing normotensive and hypertensive placentas (5,6). Fibrinoid necrosis, another hallmark of vascular pathology in hypertensive placentas, was more pronounced in eclampsia cases, aligning with evidence of endothelial dysfunction and hypercoagulability (7,8).

Syncytial knots, indicative of accelerated villous maturation and hypoxia-induced cellular turnover, were also observed in significantly higher frequency in eclampsia (9). This agrees with the study by Roberts et al., who demonstrated excessive syncytial knotting as a marker of placental stress in severe preeclampsia (10).

One of the strengths of this study lies in its integration of immunohistochemical analysis. VEGF and PlGF, essential for placental angiogenesis, were significantly reduced in eclampsia samples. VEGF promotes vasculogenesis and capillary permeability, and its downregulation leads to poor placental vascular remodeling (11). PlGF, produced by syncytiotrophoblasts, is similarly involved in placental development, and its depletion has been linked with increased disease severity (12). Our results confirm that lower VEGF and PlGF levels are associated with the progression from preeclampsia to eclampsia.

Conversely, sFlt-1 was markedly elevated in eclampsia, supporting the antiangiogenic theory of pathogenesis. sFlt-1 binds circulating VEGF and PlGF, reducing their bioavailability and impairing endothelial function (13). A rising sFlt-1/PlGF ratio is now widely regarded as a predictive marker for severe preeclampsia and imminent eclampsia (14,15). These molecular findings correlate well with the histological severity noted in the current analysis.

The findings highlight the utility of combining traditional histopathological markers with immunohistochemical profiles for a more accurate assessment of disease severity. This dual approach could aid in early diagnosis and risk stratification of hypertensive pregnancies, especially in resource-limited settings where clinical indicators alone may be insufficient.

However, the study has limitations, including a relatively small sample size and absence of a normotensive control group. Further large-scale studies are warranted to validate the biomarker thresholds and their clinical applicability.

In conclusion, this study reinforces the central role of the placenta in the pathogenesis of preeclampsia and eclampsia. The greater frequency of structural abnormalities and the dysregulation of key angiogenic biomarkers in eclampsia underline the progressive nature of placental damage. Early histological and molecular evaluation of the placenta can offer valuable insight into disease prediction and management.

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