Pre-eclampsia refers to the development of hypertension and proteinuria or hypertension and significant end organ dysfunction, with or without proteinuria after 20 weeks of gestation, or in the postpartum period in a previously normotensive woman [1]. The global prevalence of pre-eclampsia is 4.6%. In Africa, it is 44.0‰ while Mboudou et al. reported a prevalence of 4.97% in Cameroon [2] [3] [4]. It is the most morbid of the hypertensive conditions in pregnancy and is the second leading cause of maternal mortality in the world, after postpartum haemorrhage [5].

Epidemiological and experimental data demonstrate that placental tissue underlies the pathophysiology and development of the disease and indicate that pre-eclampsia is reversible within days to weeks of placental delivery [6] [7]. In pre-eclampsia, cytotrophoblast cells infiltrate the decidual portion of the spiral arteries but fail to penetrate their myometrial segment, resulting in the abnormal development of large, tortuous vascular channels which are created as the elastic muscularis is replaced by fibrinoid material [8]. Thus, the vessels remain narrow leading to hypoperfusion, hypoxia, placental ischaemia, and the eventual release of anti-angiogenic factors into the maternal circulation. This release is in turn responsible for a generalised endothelial disease which explains the symptomatic variety in pre-eclampsia [9] [10].

Classically, placental hypotrophy is the main macroscopic lesion identified in pre-eclampsia. This however remains controversial as hyperplacentotic states are usually associated with PE. Microscopically, the main parenchymal finding in pre-eclampsia is acute arteriosis. This is marked by fibrinoid necrosis of the vascular wall with an accumulation of lipid-laden “foamy” macrophages and a mononuclear perivascular infiltrate [11]. Vascular ectasia and thrombi may also be present. Pathologically, the diagnosis is made by examining the vessels of the decidua parietalis, a procedure which is usually difficult to perform in routine practice as it requires curettage. This difficulty justifies the interest in the other placental manifestations of pre-eclampsia such as villous hypoplasia, and placental infarcts, which indicate maternal vascular hypo-perfusion, and which constitute associated or progressive forms of placental pathology [12].

The absence of data describing the histopathological aspects of placental lesions in pre-eclampsia in a typically African population (Cameroon), motivated our desire to carry out this cross-sectional analytical study.

In total, we recruited 101 patients, 40 with MPE (group 1) and 61 with SPE (group 2).

In our study, we investigated placental lesions in pre-eclamptic women and sought to determine whether these lesions correlated disease severity. The pre-eclamptic patients had a mean age in the environs of 30 (29.93 ± 7.36 vs 28.28 ± 7.18) and a low socioeconomic level, with no statistically significant difference between the two groups. Several authors in the literature have reported similar results [22] [23]. In their studies, Silva et al. and Lamminpää et al. reported that a low socioeconomic status increased the risk of developing PE by a factor of 5 (OR: 4.91; 95% CI: 1.93, 12.52), while advanced maternal age (reproductive age) increased the risk of PE by a factor of 1.5 in a population of nearly 18000 women [24] [25]. This is thought to be due to decidualisation abnormalities linked to advancing maternal age, while the low socioeconomic status is associated with poor pregnancy follow-up, as well as other risk factors for PE [26] [27].

Most of the patients in our study had a parity of less than or equal to 1 (n = 0.55; 54.5%) in line with the median parity of the study which is 1.00 (IQ: 1.00 - 3.00) with no significant difference between the two groups (p > 0.05). This is consistent with the literature on pre-eclampsia which states that nulliparity and primiparity are established risk factors for pre-eclampsia. This is thought to be related to the lack of immune adaptation to pregnancy, the higher insulin resistance in primiparous women, as well as angiogenic and genetic factors [28].

Lack of pregnancy follow-up was the main factor significantly associated with severe pre-eclampsia in our study. Indeed, regular prenatal follow-up would prevent pregnant women from developing severe forms of pre-eclampsia through primary prevention (low dose aspirin, calcium) and early identification, management and monitoring of mild forms of PE [29] [30] [31] [32]

Patients with SPE had a significantly smaller mean placental weight than patients with MPE (454.37 ± 121.96 vs 511.67 ± 125.01; p = 0.024). Similar results were found by Rehman et al., Kishawa et al., and Dahlstrϕm et al., although the latter compared patients with PE to those without PE [33] [34]. In our study, the gestational ages at placental delivery were comparatively similar in both groups (36.46 ± 3.68 vs 37.55 ± 3.08; p = 0.126), a finding which points to the effect PE severity on placental weight. Indeed, in pre-eclampsia, the failure of trophoblastic invasion and the resulting poor villous development are thought to be responsible for low placental weight.

The phenomena referred to above, result from the lack of molecular oxygen sensing, signalling, or the presence of extremely low oxygen levels in the intervillous spaces before the antioxidant responses become optimal. Thus, poor oxygen sensing would contribute to problems in the development of the fetoplacental vasculature and failure of maternal spiral artery invasion and remodelling. The change in oxygen content would be induced not only by the decrease in blood flow to the placenta, but also by the narrowing of the lumens of the spiral arteries, resulting in an increase in blood flow velocity (velocity flow). These alterations damage the fragile villi tree leading to excessive excretion of aponecrotic trophoblast fragments, inflammation, oxidative stress and ischaemia by hypoxia-reoxygenation phenomenon [35]

Placental lesions of pre-eclampsia (accelerated villous maturation, infarction, large syncytial nodes) were significantly present in patients with SPE compared to the MPE group (p < 0.001). In addition, confounding lesions such as calcifications were significantly higher in patients with SPE. Several authors have reported similar findings in the literature [36] [37] [38]. Weiner et al., found a greater number of placentas with a weight below the 10^th percentile and a mix of lesions due to defective maternal vascular perfusion (accelerated villous maturation, infarction, large syncytial nodes) in the SPE group compared with the MPE group (p < 0.001). Furthermore, following multivariate analysis, these composite placental lesions were independently associated with SPE (aOR = 1.75; 95% CI 1.4 - 4.9; p < 0.001).

Chronic malperfusion eventually leads to placental infarctions (Figure 3). These consist of collapsed maternal intervillous spaces and necrotic villi usually involving the maternal floor. These findings are not specific to PE and can occur with other conditions such as uterine anomalies, maternal cardiovascular disease and inherited or acquired maternal thrombophilias. Peripheral infarcts on the maternal face of the placenta are common at term and are usually not clinically significant if small. Perinatal morbidity is associated with infarcts representing more than 5% of the placental mass or having a diameter greater than 3 cm. The infarcts are considered clinically severe (e.g., associated with foetal growth restriction or in utero foetal death) if 20% or more of the placenta is affected [11].

Specific histopathological findings that correlate poor maternal vascular perfusion include increased syncytial nodes (>1 in 3 - 5 terminal villi and/or >10 nuclei per node) (Figure 4), large syncytial nodes, villous agglutination (microinfarcts with villi collapsing on top of each other, especially in the centre of the parenchyma not involving the maternal surface), distal villous hypoplasia or accelerated villous maturation (reduced number of intermediate villi resulting in increased inter-villous space) (Figure 1), increased inter-villous fibrin (filling the lamina), and sclerotic narrowing of the arteries, arterioles, and intermediate trophoblast sheets along the basal plate [11]. However, the significance of these findings and their relationship to clinical disease is unclear.

Regarding calcifications (Figure 2), calcium deposits in the fibrin floor and septa are a normal finding associated with feeding and placental maturity at term and post-term. Villous calcification, however, is seen in villous necrosis with excessive peri-villous fibrin deposits, which may be associated with pathological conditions such as infarction, CMV infection, thrombosis and foetal death. When observed in preterm placentas, calcification of the floor and septa is attributed to senescence and therefore considered a feature of placental insufficiency [11].

Our study had some limitations. First the absence of sufficient funding prevented us from having a larger sample size necessary for more conclusive results. None the less, our findings were still valid. Also, other chronic placental conditions might have been linked to the placental lesions we described in our study.

PE remains a frequent pathology with dire consequences for the mother and the foetus in our context. Also, in line with our interests in identifying placental histopathological lesions, it appears that there are a set of composite lesions linked to underlying inadequate maternal vascular perfusion, especially in the severe form of the disease.

All authors agree to the submission of this article

Essiben Felix and Ayissi Gregory designed the study and undertook data collection. Essiben Félix, Belinga Etienne and Foumane Pascal participated in the study design, performed data edits and statistical analyses, wrote the draft, and reviewed and finalized the manuscript. Ndolo Kondo Astrid, Ngo Dingom Madye and Ebong Cliford participated in statistical analyses, and edited and reviewed the final manuscript. Ojong Samuel Atomveng revised the document. All authors read and approved the final manuscript.

The authors declare no conflicts of interest regarding the publication of this paper.

Essiben, F., Gregory, A., Etienne, B., Astrid, N.K., Ange, N.D.M., Ebontane, E.C., Atomveng, O.S. and Pascal, F. (2022) Histopathological Aspects of Placental Lesions in Mild and Severe Pre-Eclampsia in a Population of Cameroonian Women. Open Journal of Obstetrics and Gynecology, 12, 154-168. https://doi.org/10.4236/ojog.2022.122016