The Hidden Side of the Story between the Placenta and Preeclampsia: Preliminary Results of a Prospective Cohort of Pregnant Women in Cameroon ()
1. Introduction
Pre-eclampsia is the leading cause of maternal mortality worldwide. It is a placental vascular pathology whose frequency and complications are highest in Africa and developing countries [1] , yet prevention of this pathology is possible. To prevent it, we need to know how to predict it. In recent years, several studies have been carried out to determine the factors that predict the disease. Doppler studies of the uterine and umbilical arteries, as well as placental volume, have been shown to be factors whose elevated resistance indexes are associated with the onset of pre-eclampsia [2] [3] [4] . Given the limited number of studies in our context, this study was conducted with a view to obtaining data specific to our population for the prediction of the occurrence of the pathology.
2. Methodology
2.1. Type of Study
We conducted a prospective multicentre cohort study from November 2022 to August 2023 at the Yaoundé Gynaecological Obstetrics and Paediatrics Hospital and the Nkolndongo Health and Social Animation Centre. Our target population consisted of all pregnant women receiving consultations in these hospitals.
2.2. Study Population
All pregnant women attending antenatal clinics who had undergone an ultrasound scan between 12 and 18 months’ gestation.
We formed two study groups:
v First group, the exposed: These were all pregnant women with an abnormal Doppler ultrasound result between 12 and 18 BSA.
v Second group, the controls: These were all pregnant women with a normal Doppler ultrasound result between 12 and 18 BSA.
2.3. Inclusion Criteria
Pregnant women attending antenatal clinics who had undergone obstetric ultrasound between 12 and 18 weeks’ gestation and who had given informed consent were included.
2.4. Non-Inclusion Criteria
We did not include patients with known diabetes, patients with chronic hypertension, patients on Aspirin, patients with chronic kidney disease, patients with multiple pregnancies.
2.5. Exclusion Criteria
Women with spontaneous or induced abortion before 20 weeks’ gestation, and gestational diabetes.
2.6. Data Collection
From the outpatient department, we approached pregnant women between 12 and 18SA. After obtaining the patient’s consent, sociodemographic and clinical data were collected, and they were then taken to the medical imaging department where ultrasound scans were performed using a Mindray ultrasound scanner. All data were collected and recorded on a data sheet. After 20SA, the patients’ BACs were taken at each cpn and BU was performed for high BACs. At the end of the study, this enabled us to create 2 groups: EP and pregnancies without EP.
2.7. Statistical Study
The data collected were analysed using SPSS software version 23.0 (Statistical Package for Social Sciences). Quantitative variables, expressed as means ± standard deviation. Qualitative variables were expressed in terms of numbers and percentages. Chi 2 test used to assess homogeneity between groups, Student’s t test used to assess homogeneity of quantitative variables. A significance threshold of less than 5% was set. The Relative Risk with its 95% confidence interval used to assess the association between variables.
3. Results
75 Patients was approached, we had 03 missed abortions, 05 patients excluded, 67 pregnant women were registered for the study. Of these, 35 had pathological Dopplers and formed the exposed group and 32 had normal Dopplers and formed the unexposed group. The mean age in the two groups was 28.4 ± 4.9 and 25.3 ± 4.9 years respectively, and the mean parity (Figure 1).
3.1. Ultrasound Characteristics of Patients
The mean IRAUD in the exposed group was higher, 0.73, than in the unexposed group, 0.49. Similarly, the mean IRAUG in the exposed group was higher than in the unexposed group, at 0.71 and 0.52 respectively. The mean IRAO in the case group was 0.83 and in the control group 0.78. Placental volume was evenly distributed with an overall mean of 115.54 mm3 (Table 1).
3.2. Evolutionary Characteristics of Patients
The occurrence of pre-eclampsia was the only variable with a heterogeneous distribution. In fact, 15 patients in the pathological Doppler group developed PE and only one in the control group, for a prevalence of 23.9% (16 patients). Most deliveries were vaginal (95.5%) and at term (91.5%) in both groups. Male newborns were more numerous in both groups and represented 61.1% of the general population. Most were eutrophic and 98.5% had an Apgar score greater than 7 at 5e minutes. All these variables were homogeneously distributed (Table 2).
3.3. Evolution of Pregnancies According to the Occurrence of Pre-Eclampsia
The vaginal delivery route was the most frequent in both groups at 95.5%. 04.5% of all babies were premature and 94% of them had a birth weight greater than
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Table 1. Ultrasound characteristics of women.
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Table 2. Pregnancy outcome according to Doppler.
2500 g. The mean GA was 38SA + 5 days with a mean birth weight of 3123.1 g and height of 50.2 cm. 97% had an Apgar greater than 7 at 5e min. The complications of EP recorded were 02 premature deliveries at 24 and 31 AU associated with severe EP and the death of one of the newborns (Table 3).
3.4. Doppler Profile of Uterine and Umbilical Arteries in the Study Population
This study enabled us to verify the existence of a link between uterine Doppler measurements and the occurrence of EP, as summarised in Table 4.
IRAUD: index of resistance of the right uterine artery IRAUG: index of resistance of the left uterine artery IRAO: index of resistance of the umbilical artery PE: pre-eclampsia GSP: pregnancies without pre-eclampsia
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Table 3. Pregnancy outcomes by stage.
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Table 4. Comparison of resistance index averages.
IRAUD: index of resistance of the right uterine artery IRAUG: index of resistance of the left uterine artery IRAO: index of resistance of the umbilical artery PE: pre-eclampsia GSP: pregnancies without pre-eclampsia.
In our study population, the mean uterine artery resistance indexes in pre-eclampsia patients (0.74 ± 0.07 and 0.68 ± 0.13) were significantly higher than those in patients with pregnancy outcomes without EP (0.58 ± 0.14 and 0.60 ± 0.14), p value < 0.001.
Increased uterine artery resistance was significantly associated with the occurrence of EP, with an RR of 8.6 (p < 0.001) for AUD and 2.8 (p = 0.01) for AUG. Patients with abnormal Doppler were therefore 13.7 (p < 0.001) times more likely to develop EP during their pregnancies than those with normal Doppler (Table 5).
3.5. Uterine and Umbilical Artery Resistance Index Values Predictive of Pre-Eclampsia
The ROC curve here presents the occurrence of pre-eclampsia as the reference category and considers pathological Dopplers as the test. We note that the area on the curve is 0.773, so our area is significant (Figure 2).
The ROC curve here presents the occurrence of pre-eclampsia as the reference category and takes placental volume as the test. We note that the area on the curve is 0.496, so our area is not significant (Table 6 and Figure 3).
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Table 5. Relationship between resistance indexes and the onset of pre-eclampsia.
RR: relative risk IRAUD: index of resistance of the right uterine artery IRAUG: index of resistance of the left uterine artery IRAO: index of resistance of the umbilical artery.
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Table 6. Predictive values of increased uterine artery resistance indexes.
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Figure 2. ROC curve of uterine arteries. Diagonal segments are generated by ties. Zone: 0.773.
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Figure 3. ROC curve for placental volumes. Diagonal segments are generated by ties. Zone: 0.496.
4. Discussion.
4.1. Sample Size
The mean age of patients with normal Doppler was 25.34 ± 4.95 years; that of patients with pathological Doppler was 28.45 ± 4.95 years. The age range most represented in the case group was 26 - 30 years, while that most represented in the control group was 21 - 25 years. These results are superimposed on those of Naguet et al. who found an average age of patients with abnormal Doppler of 28.1 ±5.4 years [5] . In the general population, 64.2% of these women were between 21 and 30 years of age. These results are similar to those of D. Boiro et al. in 2018 and Mariem Sidi Mohamed et al. in 2017, who respectively found an average age of 27.5 years and 29.16 years, with extremes ranging from 16 to 47 years and 15 to 47 years [6] [7] . This could be explained by the fact that this is a period of intense reproductive activity for women.
4.2. Ultrasound Characteristics of Patients
In the abnormal Doppler group, the mean values for IRAUD and IRAUG were significantly higher than those for the normal Doppler group, at 0.73 (±0.078) and 0.71 (±0.13) respectively (p < 0.01). Similarly, the means of the RAOIs were significantly higher in the case group than in the control group. The difference in placental volumes, on the other hand, was not significant in the two groups, p = 0.62. M. Para-Cordero et al. in Chile in 2016 found similar results to ours. The difference in means in the two groups was significant, higher in the case group than in the control group [8] .
4.3. Pregnancy Outcome
Regarding the uterine and umbilical artery Doppler results, 52.20% were pathological and 48.80% were normal. 15 women in the case group developed EP and 1 in the control group developed EP. This gives a prevalence of EP of 23.9%. This result is higher than that of H Essome et al. at Hôpital Laquintinie and Benjelloun et al. in Greater Cassablanca, who found a prevalence of 6.12% and 07% respectively. This could be explained by the small size of our sample compared to theirs [9] .
4.4. Doppler Profile of Uterine and Umbilical Arteries in the Study Population
In the EP group, the mean values for IRAUD and IRAUG were significantly higher than those for the group of pregnancies without pre-eclampsia, at 0.74 (±0.078) and 0.68 (±0.13) respectively (p < 0.01). These results are similar to those of K Harrington et al. who found mean resistance indices of 0.80 [2] . An increase in RI was significantly associated with the occurrence of EP, with a relative risk of 13.7 and a p-value < 0.01. M. Para-Cordero et al. in 2016 in Chile found similar results. An increase in the vascular characteristics of the uterine arteries used was significantly associated with the occurrence of EP. [8] . Similarly, K. Harrington et al. and G. Okwudire et al. found similar results [3] . These results are in line with the literature. During a normal pregnancy, CTEV cells from the placenta invade the uterus (decidua and myometrium) and also the uterine arteries, mainly the spiral arteries. Following this invasion, the smooth muscle and endothelial cells of the arteries disappear, leaving the VTEC in their place. The arteries become atonic, insensitive to vasoactive molecules, which enlarges their diameter and improves perfusion of the intervillous chamber [10] . However, during a pre-eclampsia pregnancy, the endo- and perivascular invasion of the spiral arteries is defective. Vascular remodelling by the CTEV does not occur. Trophoblastic cells do not replace smooth muscle and endothelial cells. The diameter of the uterine spiral arteries remains unchanged and they retain their vasoconstrictor capacity. This lack of trophoblastic invasion and uterine remodelling leads to an increase in resistance in the uterine arteries, reduced vascularisation of the uteroplacental unit and placental hypoxia.
The mean IRAO was 0.83 (±0.08) and the difference with the opposite group was not significant (p = 0.155). This result is in total contradiction with the literature; it should be noted that the umbilical artery transports blood from the foetal heart to the placenta. EP is responsible for an increase in resistance in the placenta and in the network downstream of the umbilical artery, which by retrograde effect will also increase resistance in this artery.
Finally, we found that the mean placental volumes in the case group were reduced compared with the controls, but the difference was not significant p = 0.42. Patients in the case group had an average of 104 mm3 and those in the control group 119.15 mm3. Estelle Perdriolle Galet et al. in 2011 found similar results to ours, placental volumes were not different between the two groups. On the other hand, Cécile Fanget et al. in 2016 in France and Andréa Suranyi et al. in 2017 in Hungary found that placental volume was significantly smaller in patients who had developed EP [11] . These differences could be explained by the small size of our sample.
4.5. Correlation between Uterine and Umbilical Artery RI Values Predictive of Pre-Eclampsia
The increase in uterine artery resistance indexes had sensitivity values of 93.7%. Specificity was 60.7% and positive and negative predictive values 42.9% and 96.9% respectively. These results are similar to those of Nadia Shahid et al. in 2021, who found good sensitivity and a good negative predictive value of 71.4% and 74.1% respectively for the increase in resistance indexes [12] . Another study by Espinoza J et al. found a lower sensitivity and positive predictive value of 36% and 11% respectively. The negative predictive value was just as high, at 98%, and the specificity higher, at 90%. Their sample size was much larger than ours, which could explain the discrepancy between some of our results [13] .
5. Conclusion
Pre-eclampsia is a preventable and predictable complication of pregnancy. This study showed that an increase in the uterine artery resistance index was the only ultrasound parameter significantly associated with the onset of PE, with good positive and negative predictive values. Uterine Doppler pathology thus increased the risk of developing pre-eclampsia during pregnancy fourteen-fold. The difference in mean placental volumes and umbilical artery resistance indexes in the two groups was not significant, so no link was found with the onset of pre-eclampsia.