The triad of placenta, fetus, and mother continues to form a composite functional equilibrium during prenatal period, and dysfunction of any one of them can jeopardize the others. The dysfunction of the placenta often could lead to preeclampsia/eclampsia [
Thus, placenta has remained the most accurate record of the infants’ prenatal experience. It is a unique and wonderful organ that arises de novo, and directly relates to the growth and development of the fetus in utero [
The histological changes in preeclamptic/eclamptic placentas include infarcts, increased syncytial knots, hypovascularity of the villi, cytotrophoblastic proliferation, thickening of the trophoblastic membrane, obliterative enlarged endothelial cells in the fetal capillaries, and atherosis of the spiral arteries in the placental bed [
Additionally, in recent years, it has been revealed that there is a clear relationship between placental pathology and intrauterine growth restriction/preeclampsia [
This study aims to determine the pathological changes of placentas from mothers with preeclampsia or eclampsia and correlate the findings with the clinical severity of the disease, placental weight, and birth weights of the newborn babies.
The study was a cross-sectional analytical study carried out from August 2011 to February 2012. It consisted of two groups of patients: the study group and the control group. Due approval was obtained from the Nnamdi Azikiwe University Teaching Hospital (NAUTH) ethics committee (Reference No. NAUTH/CS/66/vol.3/93; approval date, 27 August 2010). The study was registered at
The control group consisted of selected women presenting to the labour ward of NAUTH for their management of labour during the same period of recruitment of the study group. The control group were screened and found to be without hypertensive disorders of pregnancy but they were matched for age (±2 years), parity (±1), and gestational age (±2 weeks) with that of the study group. Placental specimens were taken from all cases and the histopathologist was blinded from the study.
The sample size of the study group was calculated based on a preeclampsia/eclampsia prevalence of 3.7% [
Preeclampsia was defined as blood pressure (BP) equal to or greater than 140/90 mmHg with proteinuria on a catheterized urine specimen of at least 1+, or a clean catch midstream urine 1+ [
We included pregnant women of gestational age ≥28 weeks, singleton pregnancies, and consenting pregnant women. Women of gestational age <28 weeks, multiple pregnancies, and parturient with diabetes mellitus were excluded from the study.
After consents were obtained, the patients in the study group were evaluated for preeclampsia and eclampsia. The patients were examined clinically for elevated blood pressure medical history, age, parity, last menstrual period, and calculating the gestational age using the first day of the last menstrual period. History of fit, headache, dizziness, blurring of vision, and upper abdominal pain and the bedside urinalysis for sugar and protein were also done. Subsequently, the patients were managed according to the labour ward and unit protocol. On delivery, the placenta was weighed after trimming the edges, and the APGAR score of the baby was also determined. Superficial fetal vessels were drained of all blood and adherent blood clots were removed from the maternal surface. The placenta was weighed on a calibrated digital device and examined for gross abnormalities. After weighing and examining the placentas, the whole placentas were placed into labeled plastic containers, containing 10% formaldehyde solution.
At the histopathology laboratory, a consultant histopathologist (blinded from the clinical outcome of each placenta) was concerned with the macroscopic and the microscopic examination of the placentas. In order to be able to reliably evaluate the villous maturation of the placenta, the pathologist was only informed about the gestational age.
The tissues were then stained using Haematoxylin and Eosin and viewed histologically. Histological variables evaluated were villous maturation, decidual arteriopathy, infarction, accelerated intervillous maturation, cytotrophoblastic proliferation, stromal oedema, stromal fibrosis, and syncytial knots. Other eventual findings were noted separately.
Descriptive analysis was done using Epi-Info 2008 version 3.5.1 (Epi-Info, Centers for Disease Control and Prevention, Atlanta, GA, USA). The results were analyzed further by using cross tabulation to identify the possible relationship between variables. Analyses were performed using trend statistics of Mantel–Haenszel test and Student’s
A total of 61 women out of 1120 labour ward admissions seen during the period of the study had preeclampsia/eclampsia. Fifty-three (4.7%) were preeclampsia while 8 (0.71%) were eclampsia. Of these women recruited in the study, 14 (23%) had mild preeclampsia and 39 (63.9%) had severe preeclampsia. The control group consisted of 122 women without preeclampsia/eclampsia.
Table
Distribution by age of patients for preeclampsia (PE)/eclampsia and control groups.
Age(YRS) | Mild PE, |
Severe PE, |
Eclampsia, |
Entire study group, |
Control, |
---|---|---|---|---|---|
<20 | 0 (0.0) | 2 (50.0) | 2 (25.0) | 4 (6.60) | 8 (6.60) |
20–24 | 5 (35.7) | 17 (43.6) | 3 (37.7) | 25 (41.0) | 50 (41.0) |
25–29 | 3 (21.4) | 10 (25.6) | 2 (25.0) | 15 (24.6) | 30 (24.6) |
30–35 | 4 (28.6) | 4 (10.3) | 1 (12.5) | 9 (14.8) | 18 (14.8) |
>35 | 2 (14.3) | 6 (15.4) | 0 (0.0) | 8 (13.10) | 16 (13.10) |
Total | 14 | 39 | 8 | 61 (100%) | 122 (100%) |
Mean age | 25.5 ± 5.3 | 25.9 ± 5.7 |
About half of the patients (43%) were primigravidae while only 3 (5%) of the patients were grandmultiparous. The mean parity of both the case and control groups was 1.3 ± 1.5 and 1.4 ± 1.5, respectively. There was also no significant statistical difference between the control and study groups in relation to parity (see Table
Distribution by parity of patients for preeclampsia (PE)/eclampsia and control groups.
Parity | Mild PE, |
Severe PE, |
Eclampsia, |
Entire study group, |
Control, |
|
---|---|---|---|---|---|---|
0 | 5 (35.7) | 17 (43.6) | 4 (50.0) | 26 (42.6) | 53 (43.4) | 0.916 |
1 | 3 (21.4) | 7 (17.9) | 2 (25.0) | 12 (19.7) | 23 (18.9) | 0.895 |
2 | 3 (21.4) | 4 (10.3) | 1 (12.5) | 8 (13.1) | 16 (13.1) | 1.000 |
3 | 1 (7.10) | 5 (12.8) | 1 (12.5) | 7 (11.5) | 15 (12.3) | 0.873 |
4 | 1 (7.10) | 4 (10.3) | 0 (0.0) | 5 (8.20) | 9 (7.40) | 0.845 |
>4 | 1 (7.10) | 2 (5.10) | 0 (0.0) | 3 (4.90) | 6 (4.90) | 1.000 |
Total | 14 | 39 | 8 | 61 (100.0%) | 122 (100.0%) |
The mean gestational age (37 vs 38 weeks;
The mean birth weight for patients with mild preeclampsia, severe preeclampsia, and eclampsia were 2.66 kg ± 1.63 kg, 2.58 kg ±1.61 kg, and 2.45 kg ± 1.57 kg, respectively, while those of the controls were 2.79 kg ± 1.67 kg, 2.75 kg ± 1.66 kg, and 2.75 kg ± 1.66 kg, respectively. There was no statistical difference in the mean birth weight between mild preeclampsia, severe preeclampsia, eclampsia, and the control groups (
Distribution of gross placental changes for preeclampsia (PE)/eclampsia and non-preeclampsia groups.
Placental changes | Mild PE, |
Severe PE, |
Eclampsia, |
Study group, |
Control, |
Trend statistics of PE, SP, and eclampsia, resp. |
---|---|---|---|---|---|---|
|
|
|
|
| ||
|
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0–5 | 9 (64.3) | 13 (33.3) | 2 (25.0) | 24 (39.3) | 107 (87.7) | 0.020; <0.001; <0.001 |
6–10 | 5 (35.7) | 6 (15.4) | 1 (12.5) | 12 (19.7) | 13 (10.7) | 0.009; 0.427; 0.871 |
11–20 | 0 (0.0) | 15 (38.5) | 2 (25.0) | 17 (27.9) | 1 (0.80) | 0.735; <0.001; <0.001 |
>20 | 0 (0.0) | 5 (12.8) | 3 (37.5) | 8 (13.1) | 1 (0.80) | 0.735; 0.001; <0.001 |
|
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|
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Absent | 4 (28.6) | 0 (0.0) | 0 (0.0) | 4 (6.60) | 79 (64.8) | 0.009; <0.001; <0.001 |
+ | 7 (50.0) | 15 (38.5) | 3 (37.5) | 25 (41.0) | 31 (25.4) | 0.053; 0.117; 0.453 |
++ | 3 (21.4) | 24 (61.5) | 5 (62.5) | 32 (52.5) | 12 (9.80) | 0.191; <0.001; <0.001 |
|
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|
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Absent | 8 (57.1) | 24 (61.5) | 4 (50.0) | 36 (59) | 73 (59.8) | 0.846; 0.850; 0.585 |
+ | 2 (14.3) | 13 (33.3) | 3 (37.50) | 18 (29.5) | 45 (36.9) | 0.093; 0.688; 0.972 |
++ | 4 (28.6) | 2 (5.10) | 1 (12.50) | 7 (11.50) | 4 (3.30) | <0.001; 0.597, 0.191 |
Relationship between degree of placental infarction and birth weight (BW).
Infarction (%) | Cases mean BW (kg) | Control mean BW (kg) |
|
---|---|---|---|
0–5 | 2.85 | 3.01 | 0.820 |
6–10 | 2.61 | 2.72 | 0.120 |
11–20 | 2.53 | 2.65 | 0.030 |
>20 | 2.26 | 2.44 | 0.010 |
The mean placental weights in the study group were 0.41 kg ± 0.64, 0.37 kg ± 0.61 kg, and 0.33 kg ± 0.57 kg for mild preeclampsia, severe preeclampsia, and eclampsia, respectively, while those of control were 0.50 kg ± 0.71 kg, 0.51 kg ± 0.71 kg, and 0.51 kg ± 0.71 kg, respectively. There was a marginal difference in the mean placental weight between the mild preeclamptic, severe preeclamptic, eclamptic, and the control groups, but not statistically different (
The fetal/placental weight ratio showed a marginal increase from mild preeclampsia to eclampsia but a similar ratio among the study groups. The mean ratio is 6.50 : 1, 6.97 : 1, and 7.42 : 1, respectively, for the study group and 5.58 : 1, 5.39 : 1, and 5.37 : 1, respectively, for controls.
The difference in the mean ratio between the severe preeclampsia, eclampsia, and the control groups was statistically significant (
The macroscopic (gross) features of the placentas were as shown in Table
All the placentas in the severe preeclampsia and eclampsia groups had some degrees of placental haematoma. The difference in the presence (two pluses) or absence of haematoma between mild preeclampsia, severe preeclampsia, eclampsia, and control groups was significant (
The incidence of calcification in the normal placentas in the present study was 40.2% (
Table
The relationship between the clinical severity of the disease and the histological findings was as presented in Table
Distribution of histological findings in relation to clinical severity of preeclampsia (PE) and non-preeclampsia groups.
Histological findings | Mild PE, |
Severe PE, |
Eclampsia, |
Control, |
|
---|---|---|---|---|---|
Stromal oedema | 5 (35.7) | 24 (61.5) | 2 (25.0) | 55 (45.1) | 0.500; 0.070; 0.460 |
Stromal fibrosis | 7 (50.0) | 19 (48.7) | 3 (37.5) | 38 (31.1) | 0.260; 0.070; 0.990 |
Syncytial knots | 7 (50.0) | 17 (43.6) | 5 (62.5) | 35 (28.7) | 0.120; 0.070; 0.070 |
Cytotrophoblastic proliferation | 6 (42.9) | 28 (71.8) | 6 (75.0) | 31 (25.4) | 0.280; 0.001; 0.010 |
Accelerated villous maturation | 8 (57.1) | 27 (69.2) | 6 (75.0) | 38 (31.1) | 0.100; 0.001; 0.001 |
Decidual arteriopathy | 9 (64.3) | 30 (76.9) | 7 (87.5) | 43 (35.2) | 0.670; 0.001; 0.001 |
The placenta has been described as the mirror of the perinatal mortality. A glance at the literature reveals that the preeclampsia-eclampsia syndrome exerts its deleterious effects on the placenta. It was found in this study that low placental weight was related to the severity of the preeclampsia/eclampsia than in the control group. However, there was no statistical difference. The average mean placental weight in the preeclampsia/eclampsia group was 0.37 kg, while the average mean weight in the control group was 0.51 kg. This compares favourably with Pandit et al.’s [
There is a linear relationship between placental weight and birth weight of baby that can be expressed by feto-placental ratio. The fetal/placental weight ratio showed a marginal increase in the diseased group, which is statistically significant between severe preeclampsia, eclampsia, and control groups (
About 25% of the normal-term placenta contained infarcts involving <5% of the placental parenchyma, but their frequency of occurrence is increased in preeclampsia and extensive infarcts being in 60-70% of patients with severe disease [
In preeclampsia/eclampsia, 50% of placentas of patients have infarcts [
Minimal infarcts are not unusual findings in placentas delivered at term and are considered to be due to placental “aging.” In preeclampsia/eclampsia, however, there is accelerated “aging,” and widespread infarcts are common findings. There are, however, no histological or ultrastructural changes in the villi that can be considered as indicative of an aging process according to Fox [
Haematoma was a consistent finding in this study as all the placentas (100%) of severe preeclampsia and eclampsia had some degrees of haematoma. The difference in the presence of haematoma between the diseased and control groups was significant (
Calcification is regarded as evidence of placental senescence or degeneration. The incidence of calcification in the normal placentas in the present study was 40.2% while the overall incidence in the diseased group was 41%. There was no significant statistical relationship between the presence of calcification in the diseased and control groups (
In the present study, the birth weight of baby was found to be decreased with increasing degree of placental infarction. Placental infarction >20% was associated with lower birth weight. There was a statistical difference between the involvement of >10% of placental surface and the birth weight (
Microscopic features observable under the light microscope include stromal oedema, stromal fibrosis, syncytial knots, cytotrophoblastic proliferation, accelerated villous maturation, and acute atherosis among others [
This study demonstrated high frequencies of decidual arteriopathy, accelerated villous maturation, syncytial knots, cytotrophoblastic proliferation, stromal fibrosis, and stromal oedema in the preeclamptic/eclamptic group compared with the control group. Only decidual arteriopathy, accelerated villous maturation, and cytotrophoblastic proliferation showed statistical significant on analysis between the severe preeclampsia, eclampsia, and the control groups (
Decidual arteriopathy was the most consistent histological finding in this study; hence, Vijay et al. [
Although hypertension is a requisite to diagnosing preeclampsia, absolute blood pressure alone is not always a dependable indicator of its severity. The histological findings in mild preeclampsia, severe preeclampsia, and eclampsia were similar; therefore, differentiation between mild and severe preeclampsia can be misleading because in clinical practice, a mild disease may progress rapidly to severe disease [
Fetal compromise is therefore generally the rule and perinatal mortality is high as reflected in a maternal mortality and a perinatal mortality recorded among eclamptics. If the mortality is expressed per number of eclamptic women, it will be one death for every eight eclamptics. It is obvious, therefore, that preeclampsia and eclampsia are major contributors to maternal and perinatal mortality in developed and developing countries [
The placenta plays a central role in the origin and pathophysiology of preeclampsia. Here, it was demonstrated that a cardinal sign of placental hypoxia, that is, infarction, correlates to the clinical severity of the disease and fetal outcome, regardless of gestational age. The occurrence of infarction was more common and the amount of infarction was greater in severe preeclampsia and eclampsia in comparison to the control group. The correlation between the amount and extent of infarction and the clinical degree of symptoms indicates that mild preeclampsia, severe preeclampsia, and eclampsia are manifestations of different maternal response, rather than just preeclampsia forms depending on different gestational ages.
Preeclampsia/eclampsia adversely influences the weight of the placenta and fetal outcome. Thus, placenta acts as an effective index by examination of which we can predict the status of fetus in neonatal life as it can act as an indicator to the overall development of the fetus in preeclamptic/eclamptic cases.
Should all placentas be sent for detailed examination of placenta if there is adverse perinatal outcome; it is still not clear whether the pregnancy and neonatal outcomes are any different in abnormal placental histology group as compared with that of normal histology.
Guidelines suggest that all placentas should be examined by the trained perinatal pathologists. Placental pathology should be a routine component of obstetric-neonatal care, as it would provide detailed information, helpful in the postnatal management of adverse pregnancy outcome. However, the histological examination and perinatal outcome in most pregnancies is normal; for example, in the current study, the frequency of histologically normal examination was observed in over 50% of cases, even in the study group only few histological lesions were seen in the majority of the placentas. Therefore, the data from this study do not support the recommendations for the routine examination of placenta by the pathologist [
Hemolysis, elevated liver enzymes, and low platelet count.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The teaching hospital ethics committee approval was obtained before the start of the work. The study protocol was approved by the Institutional Review Board of the Nnamdi Azikiwe University Teaching Hospital (NAUTH) ethics committee (Reference No. NAUTH/CS/66/vol.3/93; approval date, 27 August 2010).
Formal written consent had been taken from each woman recruited for the work for both sharing the work and publishing the work.
The authors declare that they have no conflicts of interest.
Dr Chijioke Ogomegbulam Ezeigwe is the owner of the hypothesis and collected the specimen from the women. Dr. George Eleje, Dr. Chijioke Ogomegbulam Ezeigwe, Prof. Charles Ikechukwu Okafor, Prof. Gerald Okanandu Udigwe, and Prof. Daniel Chukwuemeka Anyiam wrote the first draft and advised on the analysis. Dr. George Eleje, Dr. Chijioke Ogomegbulam Ezeigwe, and Prof. Charles Ikechukwu Okafor were responsible for data processing and final editing. All authors contributed to the discussion and conclusion.
The current work had taken great efforts from all colleagues who work in the Nnamdi Azikiwe University Teaching Hospital, who kindly participated in the case management and specimen collection. Great thanks are due to all who shared and helped to put this work in its final form.
Plate 1: photomicrograph showing the placenta from the eclampsia group. Plate 2: photomicrograph showing the placenta from the severe preeclampsia group.