Three Dimensional Power Doppler Ultrasound in Assessment of Placental Volume and Blood Flow and its Correlation with Severity of Pre-Eclampsia

Background: Pre-eclampsia [PE] is a main reason for maternal and perinatal morbidities and mortalities. Three-dimensional power Doppler ultrasound [3DPD-US] methods nowadays give a noninvasive way of evaluating placental vascularization, flowing and vascularization-flowing indices. The specially designed VOCAL software, used in this technique, can calculate special indices and virtually reconstruct vascular tree within the given tissue volume. Aim of the work: To evaluate the use of three-dimensional power Doppler [3DPD] ultrasound [US] in assessment of placental size and blood flow and its correlation with severity of pre-eclampsia. Patients and Methods: This is a cross-sectional study which included 100 pregnant females with pre-eclampsia who had admitted to the Obstetrics and Gynecology Department of Bab-Alsheiria University Hospitals at the last antenatal care visit before delivery. The sample size was further allocated into 2 groups, each containing 50 cases, according to the severity of preeclampsia: the severe group and the mild group. Results: There was a significant decrease in the placental volumes and blood flows among the studied groups. All three indices measuring vascularization index [VI], flow index [FI] and vascularization flow index [VFI] were revealed to be significantly higher in the mild group in comparison with the severe group. Conclusion: 3DPD-US can give novel insights into valuation of placental volumes and blood flow and its correlation with severity of preeclampsia.


INTRODUCTION
Preeclampsia is the main cause of maternal and perinatal morbidities and mortalities described as the incidence of high blood pressure and substantial proteinuria in formerly healthy women on or after the 20th-wk of pregnancy. It happens in around 2-8% of all pregnant women [1] .
Preeclampsia is defined according to ACOG guidelines as permanent BP 140-mmHg systolic and/or diastolic 90-mmHg happening after the 20th-wk of pregnancy and proteinuria > 0.3-g/day or entire protein/creatinine ratio > 0. 3 [or 1+ proteinuria on urine dip stick examination on at least 2 occasions] [2] .
Three-dimensional power Doppler ultrasound [3DPD-US] methods nowadays give a noninvasive way of evaluating placental vascularization and flow indices; vascularization, flowing and vascularization-flowing indices. 3DPD-US may describe interior placental vessel features like densities of vessels, branching, caliber variations, and tortuousness [3] .
3D-US can give upgraded visualizations of embryonic anatomy in comparison to conventional two-dimensional [2D] US scanning. Subsequently, the introduction of 3DUS could simplify the new evaluation of the placenta, like surfacerendering scanning and size measurements. With the new developments in 3DPD-US, in addition to quantitative 3DPD histogram analysis, qualitative and quantitative evaluations of the vascularization and blood flow of the placenta have been possible [3] .
The combinations of power and color Doppler sonography measures blood movements in very small vessels and allows calculations of their impact on the total perfusion of a given placenta size. These indices are computed via built-in algorithms in the VOCAL [Virtual Organ Computer-aided Analysis] package [3] .

AIM OF THE WORK
To detect differences in placental condition regarding volume, vasculature, and blood flow between Mild and Severe Preeclampsia using 3DPD-US.

PATIENTS AND METHODS
This is a cross-sectional research which included 100 pregnant females who had presented and admitted to the Obstetrics and Gynecology Department of Bab Alseheiria University Hospitals at the last antenatal care visit before delivery. The study was done over a period of 6 months starting from Jan 2021 to June 2021. The sample size was further allocated into 2 groups, every one containing 50 cases, according to the severity of preeclampsia: severe group and mild group.
Diagnostic criteria for mild preeclampsia: Preeclampsia was identified as high BP [140/90 or more] on at least 2 occasions, 6 hours apart, first recognized in this pregnancy, and detected after 20 weeks of gestation, together with proteinuria [> 300 mg in 24 hr urinary proteins, or albumin+1 or higher in complete urine analysis] [4] .
Criteria of severity of preeclampsia: Severe preeclampsia was defined if any of the following severe features are present: systolic BP >160 mmHg or diastolic BP >110 mmHg, while the patient at bed rest, on two occasions, at least 4 hours apart [unless anti-hypertensive therapy is initiated before this time]. Other features of severity include: thrombocytopenia [platelet count < 100,000], abnormal liver function [elevated blood levels of liver transaminases to twice the normal concentration, severe persistent right upper quadrant or epigastric pain unresponsive to medication and not explained by alternative diagnoses, or both], new growth of renal insufficiency [elevated serum creatinine greater than 1.1 mg/dl, or doubling of serum creatinine in the nonexistence of other reversible causes], new-onset cerebral or visual abnormalities, or pulmonary edema [4] .
Inclusion criteria: Pregnant women in the 3rd trimester [> 26wks], singleton pregnancy with normal fetal morphology and diagnosed with pre-eclampsia were included. The study groups were evaluated for full history of obstetric and gynecological history. Physical examination included vital signs and abdominal examination for determination of fetal lie, position and size. Laboratory investigations included complete blood picture with platelet count, liver enzymes, serum creatinine levels and 24-hour urine proteins.

Ethical considerations
Verbal and written informed consents were taken before the start of the study. The presented study was approved by the Research and Ethical committee, Faculty of Medicine-Al-Azhar University.

Statistical analysis
Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. [Armonk, NY: IBM Corp]. Qualitative data were described using number and percent. The Kolmogorov-Smirnov test was used to verify the normality of distribution. Quantitative data were described using range [minimum and maximum], mean and standard deviation. Chi-square test was used for categorical variables, to compare between different groups, Student ttest was used for normally quantitative variables, to compare between two studied groups, and Mann Whitney test was used for abnormally quantitative variables, to compare between two studied groups. Significance of the obtained results was judged at the 5% level. There was significant elevation of ALT, creatinine and 24h urinary proteins among patients with severe preeclampsia [ Table 2].

Patients
On Comparison between two groups as regard to patients' vascularization index, In the Flow index, vascularization flow index; there was statically significant difference among the studied groups [ Table 3].

DISCUSSION
Quantitative 3DPD analysis was utilized to evaluate placental perfusions and vascularization indices that mirror both utero-placental and feto-placental blood perfusions. Direct investigations of the perfusion of in vivo placentae have been feasible. Even every small blood motion within the studied size may be recorded by a mixture of power and color Doppler sonography reflected by these indices [3] .
The three indices or parameters assessing placental perfusion and vascularization are the vascularization index [VI], which is the determination of the percentage of vascularized tissues. The Vascularization flow index [VFI] measures the relative amount of moving blood in the sampled tissues. FI [Flow index] measures the amplitude of the blood movements in the sampled placental site [3] .
De Paula et al. [6] demonstrated that all placental vascular indices assessed via 3DPD presented a persistent distribution during pregnancy in spite of the rise in placenta volume in accordance to pregnancy age. In the present study, we revealed a significant association [P-value 0.05] between gestational age and severity of preeclampsia and placental volume. In another study, by Moran et al. [7] , there was no correlation between size and gestational age among pre-eclampsia patients. In the same study, VI and VFI aren't impacted by pregnancy, but FI was detected to rise with pregnancy age. All 3 indices were less than standard values in-between 24-and 30-wks. This is in accordance with the present work as the three indices were found to be significantly lower than the reference limit, although pregnancy was in the third trimester in both non-severe and severe groups. This placenta volume could only be a prognosticator of the severity of preeclampsia.
In contrast to our studies, Rizzo et al. [8] performed prospective observational research on 32-pregnancies at the 1st trimester of gestation to evaluate placental volume. They found a non-significant change in the placenta volume when compared to the reference limit. A change in the number of preeclampsia patients in the studied groups could play a role in the different results.
The present work was performed to determine the placenta vascularization in the third trimester of gestation and its connection with pre-eclampsia severity. All three indices measures VI, FI and VFI were revealed to be high significantly in the non-severe group in comparison with the severe group.
As in the present study, Yuan et al. [9] stated that all 3DPD indices had a significant relationship with gestation age, and FI, VI, and VFI of the placenta were significantly lower in the severe preeclampsia group in comparison with the ordinary group. Furthermore, in accordance with our results, they stated that there was a significant decrease in VI and VFI vascular indices comparing the non-severe and severe groups of preeclampsia. In comparison with normotensive cases, cases with severe pre-eclampsia had a significant decrease in placenta VI & VFI. There is marked similarity with the results of the present work as comparison of VI in the non-severe group to normal reference value showed a non-significant decrease in our work.
Thus, according to Yuan et al. [9] , intra-placental vascularization was worse in females with severe preeclampsia, while damage to placenta vessels may be relatively mild in non-severe preeclampsia.
The findings of the present work were in agreement with Chen et al. [3] , who stated that all three indices were significantly lower in severe pre-eclamptic placenta in comparison with control and that the severity of preeclampsia couldn't be expected by vascular indices.
Mercé et al. [10] found an increase in VI, FI and VFI with a positive correlation with gestational age, but this author identified only a portion of the placenta with the maximum density of vessels, a technique called vascular placental biopsy.
These results are in contrast to Guiot et al. [11] , who found a decrease in VI, FI and VFI. This could be due to the fact that they calculated vascular indices in five constant regions of the placenta.
In contrast to the present study, the results of Suranyi et al. [12] , reported lower VI in gestations complicated by preeclampsia in comparison with controls, though the change was non-significant.
Our objective was to examine volume and placental vascularization in both non-severe and severe groups of preeclampsia in the third trimester. A decrease in measured parameters in both groups was seen, which can help in detection of preeclampsia. Therefore, we may decide about managing and monitoring strategies.
3DPD sonography can give new visions into placenta pathophysiology. Additional research is desired to determine its accuracy when utilized in clinical practices as a supernumerary or an assistant to umbilical artery Doppler. Also, possible correlation with clinical biomarkers during preeclampsia such as soluble fms-like tyrosine kinase 1 [sFI/t-1] or placenta growing factor [PIGF] could help in management. In spite of multiple publications and journal submissions using 3DPD, the consistency and reproducibility of parameters are still suspected. Fixed reference values for prognosis and management are still lacking.

CONCLUSION
3DPD-US can give novel insights into evaluation of placental volumes and blood flow and its correlation with severity of preeclampsia. Additional research is desired to confirm its accuracy when utilized in clinical practices. In this study, a comparison between mild and severe pre-eclamptic patients as regards placental volume showed that there was a significant decrease in the placenta size among the studied groups. We revealed a non-significant association [P-value > 0.05] between gestational age and the volume of the placenta regarding the severity of preeclampsia. All three indices measuring VI, FI and VFI were revealed to be significantly higher in the mild group in comparison with the severe group.

Financial and Non-financial Relationships and Activities of Interest
None