Key-words:
Clinical correlates - gross lesions - microscopic lesions - placental lesions - preeclampsia
Introduction
Hypertensive disorders of pregnancy are a leading global cause of maternal, fetal, and neonatal morbidity and mortality with a prevalence of 2%–17% in Nigeria.[[1]],[[2]],[[3]] Preeclampsia/eclampsia is a multiorgan spectrum of diseases characterized by onset of hypertension (systolic ≥140 mmHg and/or diastolic ≥90 mmHg) after 20-week gestation and significant proteinuria (>0.3 g per 24 h or ≥2+ proteinuria, detected by urine dipstick).[[1]] Eclampsia is a complication of severe preeclampsia characterized by convulsions with its attendant increased complications.[[2]] Theories of pathogenesis of preeclampsia include abnormal placentation and reduced placental perfusion leading to widespread dysfunction of the maternal vascular endothelium and accompanying hypertension.[[4]],[[5]],[[6]] This includes defective invasion of the spiral arteries by the cytotrophoblast and defective spiral artery remodeling.[[7]],[[8]] Preeclampsia can range from mild to severe and the clinical presentation may range from asymptomatic mild cases to multiorgan failure.
Researchers have reported both gross as well as microscopic pathological findings in the placentae of babies born to women with preeclampsia/eclampsia.[[9]],[[10]] However, such reports are limited in low-income countries especially sub-Saharan Africa partly due to the social, cultural, and religious beliefs associated with the placenta in these areas such that most families do not readily release the placenta for research purposes. This study aimed to evaluate placental changes and the perinatal outcomes among women with preeclampsia/eclampsia and compare to normotensive pregnant women in a low-income country.
Materials and Methods
Study setting
The study was conducted at the University of Ilorin Teaching hospital which is a tertiary health facility in North central Nigeria with an average number of 43 deliveries/week.
Study period
The study period spanned from January 1, 2018 to November 30, 2018.
Study design
The study design was a comparative study.
Study participants
Participants were pregnant women aged 18–40 years at 28–41 weeks of gestation who were admitted for delivery categorized into study group (women with preeclampsia/eclampsia) and control group (normotensive women) after matching for maternal age and gestational age.
Inclusion criteria
Pregnant women at 28–41 weeks who were admitted for delivery and delivered at the study center during the study period who consented to participate in the study.
Exclusion criteria
Women whose pregnancy ended before the 28th week or beyond the 41st week of gestation were excluded from the study.
Sample size determination
The sample size was calculated using the formula[[11]]
Where: N = sample size
z = standard normal deviation (a constant which is 1.96 at 95% confidence interval)
P = prevalence of preeclampsia at the study site i.e., 0.05 (5%)[[12]]
d = observed difference at 0.05 (5%) level of significance.
q = 1 − P = 1–0.05 = 0.95
Thus, a minimum sample size of 73 was recruited into each arm of the study to give a total number of 146 participants.
Sampling method
Purposive nonprobability sampling was employed.
Study procedure
Participants were screened and educated about the study at the delivery, antenatal, and emergency wards of the Obstetrics and Gynaecology Department; eligible and consenting women were recruited into the study, and a written informed consent was obtained from all participants. All participants were monitored, and labor was managed with partograph with routine intrapartum management; at delivery, the birth weight, and APGAR scores were noted, blood clots were removed from the placenta, they were weighed within 1 h after delivery after examination for completeness, gross abnormalities in the umbilical cord, fetal membranes, and the placenta disc. Full thickness sections were taken from the central areas of each placenta and a section of the membranes (membrane roll) and additional sections were taken from grossly abnormal areas when present. The sections from the fresh placentae were fixed and processed for paraffin sections; staining of the sections was with H and E. Special (histochemical) stains used included Masson's Trichrome to demonstrate the presence of fibrosis, and Periodic Acid Schiff to demonstrate the basement membranes of placental/villous vessels. The mothers and their newborn received routine postpartum care as indicated for each mother–baby pair.
Primary outcome measure
The primary outcome measure was placental characteristics, i.e., placental weight, gross, and microscopic abnormalities.
Secondary outcome measure
The secondary outcome measure was the perinatal outcome.
Data management
The study data were collected using a data collection sheet designed for the study and entered into the computer. Descriptive statistics were presented as frequency, percentages, and mean. Chi-square was used to compare categorical variables. T-test was used to compare continuous variables and Yates corrected Chi-square (y) was used where applicable. Analysis was performed using SPPSS version 23.0 (IBM, Armonk, NY, USA) and P < 0.05 was termed significant at 95% confidence interval.
Ethics
Ethical approval was obtained from the ethical review committee of the University of Ilorin Teaching Hospital (Approval number: NHREC/02/05/2010. Date: January 11, 2017), and written informed consent was obtained from all participants.
Results
There were 1575 deliveries during the period of the study, 81 women had preeclampsia/eclampsia giving a prevalence of 5.14%; 25 (34%) had mild preeclampsia, 32 (44%) severe preeclampsia, and 16 (22%) eclampsia. [[Table 1]] shows that the study group had significantly higher preterm delivery (36 vs. 20; P = 0.029), lower mean gestational age at delivery (37.04 ± 2.32 vs. 38.48 ± 1.28; P ≤ 0.001), higher caesarean delivery (30 vs. 2; P ≤ 0.001), smaller mean placenta weight (556.82 ± 16 vs. 649.93 ± 116.38; P ≤ 0.001), higher gross placenta infarction (12 vs. 0), low first (36 vs. 6; P ≤ 0.001), and fifth (15 vs. 0; P ≤ 0.001) min APGAR scores as well as neonatal mortality (8 vs. 0; P = 0.004) compared to control group.
Table 1: Obstetric and neonatal parameters
[[Table 2]] shows that 11 microscopic placental changes were identified in the placentae of the control group compared to 4 in the study group, while all the microscopic placenta changes except acute chorioamnionitis were significantly higher in the study group. Among babies born to mothers in the study group, microscopic changes such as decidual vasculopathy (P = 0.049), incomplete vascular remodeling (P = 0.019), accelerated villi maturity (P = 0.049), acute chorioamnionitis (P = 0.048), and microcalcifications were significantly associated with abnormalities in the APGAR scores at birth.
Table 2: Presence of microscopic placental changes among study participants and the effect on 5th min APGAR scores of study group
[[Figure 1]] shows that the microscopic placental abnormalities increased with the severity of preeclampsia being higher for severe compared to mild preeclampsia.
Figure 1: Microscopic placental parameters and disease severity
[[Figure 2]] shows that the highest number of perinatal mortality (6) was reported among babies whose placentas showed stromal fibrosis (6/50); incomplete vascular remodeling was associated with four deaths (4/9), while all babies (3) with features of acute chorioamnionitis on their placentas died (3/3).
Figure 2: Relationship between microscopic placenta parameters and perinatal mortality
Discussion
The incidence of preeclampsia/eclampsia in this study was comparable to a report of 5% in a previous study at the study center;[[12]] it was however higher than 1.2% from Calabar[[13]] and lower 8.8% from Jos[[3]] all in Nigeria. This further confirms the variations in the incidence of preeclampsia across different regions in the same country.
The overall mean placental weight in women with preeclampsia/eclampsia was significantly lower than those of the normotensive women. This is similar to reports from Southeast Nigeria,[[14]] Croatia[[15]] and India;[[10]],[[16]] this may be attributed to the occurrence of placental abnormalities and reduced function and eventual effect on placental growth and function.
Gross placenta infarcts were reported in the placentae of women with preeclampsia/eclampsia unlike normotensive women in this study. A previous study in Nigeria reported 59% incidence of gross infarcts in the placentae of preeclamptic mothers,[[14]] while 66% was reported among women with preeclampsia compared to 8% among normotensive controls in a study from India.[[18]] The lower incidence of gross infarcts observed in this study may be attributable to the study design which allows examination of fresh placentae unlike studies which examined formalin preserved samples because fixation in formalin makes it easier to quantify the extent of infarction.[[19]],[[20]] Other reports showed that gross placental infarcts are common and are not necessarily pathologic except in cases of multiple or extensive infarcts occupying more than 5% of the placental surface.[[14]],[[17]]
The report of many microscopic placental lesions among women with preeclampsia/eclampsia in this study included stromal fibrosis (68.5%), increased syncytial knotting (65.8%), infarction (30.1%), decidual vasculopathy (15.1%), accelerated villi maturity (15.1%), and incomplete vascular remodeling (12.3%). This compares to the observation of Moldenhauer et al. who reported that decidual arteriolopathy, villi hypermaturity, intervillous thrombi, and central infarction were significantly higher in the placentae of women with preeclampsia compared to normotensive women.[[21]] Similarly, a systematic review of histopathological changes in preeclampsia done in the UK reported villous lesions in 48.2% of pregnancies with preeclampsia and 11.6% of normotensive pregnancies, while vascular lesions were recorded in 37.3% of preeclampsia relative to 8.1% of normal pregnancies.[[22]]
There were observed relationship between disease severity and microscopic findings of incomplete vascular remodeling, villi immaturity, and calcifications in the placentae, especially among women with severe preeclampsia/eclampsia in this study. The absence of incomplete vascular remodeling in the placentas of normotensive women and those with mild diseases affirms its association with the severe spectrum of preeclampsia. Decidual vascular changes have been reported as the most specific lesions and the possible underlying causes of other pathologies such as infarction and abruption in women with maternal hypertensive disorders.[[23]] Although only three women had microscopic features of acute chorioamnionitis in this study, all were in women with preeclampsia/eclampsia and all resulted in perinatal mortality This may be due to the attendant fetal inflammatory response syndrome associated with the condition.[[22]],[[23]]
Eight (11%) perinatal mortality was recorded in this study and all were in women with preeclampsia/eclampsia; this corroborates a similar report from Madagascar which reported a perinatal mortality rate of 11.34% attributable to placental insufficiency.[[24]]
It is worthy of note that many newborns with microscopic placental abnormalities had good APGAR scores at birth and survived. While this may be related to the promptness of delivery and available neonatal resuscitation of the affected women,[[25]],[[26]] it further suggests that the presence of placental microscopic abnormalities is not an absolute factor for adverse perinatal outcomes. Therefore, future research should explore the role of the number, types, and grade of the microscopic pathologic abnormalities, maternal disease severity, and individual fetal and neonatal factors on the perinatal outcomes.
Conclusion
This study concludes that both gross and microscopic placental changes are associated with pregnancies complicated by preeclampsia/eclampsia with attendant increased risk for adverse perinatal outcomes. Therefore, antepartum fetal surveillance should be escalated to prioritize the characterization of placenta features using Doppler ultrasonography in the fetuses of such women in order to appropriately plan the delivery.
