VALUE OF 3-D USS OF PLACENTAL VOLUME, UTERINE AND UMBILICAL ARTERY DOPPLER IN PREDICTION OF PRE-ECLAMPSIA

VALUE OF 3-D USS OF PLACENTAL VOLUME, UTERINE AND UMBILICAL ARTERY DOPPLER IN PREDICTION OF PRE-ECLAMPSIA

By

Soha Farid Fahim Hassan, Abd El-Moneim Zakaria and Sameh Saeed Faraj

Department of Obstetrics and Gynecology, Faculty of Medicine, Al-Azhar University

Corresponding author: Soha Farid Fahim Hassan,

E-mail: soha_fahim@yahoo.com

ABSTRACT

Background: Preeclampsia is a multisystem disorder of pregnancy defined by the combination of new-onset hypertension and proteinuria that contribute substantially to perinatal morbidity and mortality worldwide. Ultrasound can currently be used in the detection of adverse pregnancy outcome for example in Pre-eclampsia where Doppler indices and spectral wave forms are used.

Objective: To use Doppler ultrasound for evaluation on of placental volume changes using 3-D USS, as well as abnormalities in uterine and umbilical artery Doppler indices in prediction of pre-eclampsia.

Patients and Methods: This study was conducted in Department of Obstetrics and Gynecology of Al-Hussein Hospital, Al-Azhar University during the periods May 2016 till April 2017. This was a prospective observational study that carried on two hundred pregnant women enrolled into two equal groups. Group "A" consisted of 50 primipara and 50 multipara women with known risk factor to develop pre-eclampsia like previous history or medical disorder such as chronic hypertension and Group "B" consisted of 50 primipara and 50 multipara women without any risk factor to develop pre-eclampsia.

Results: There was no statistically significant difference between both groups as regard to umbilical artery pulsatility index (PI), while umbilical artery resistance index (RI) and abnormality have higher statistically significant values in group A. There was a statistically significant difference between both groups as regards uterine artery PI, RI, abnormality and persistent notch (p value= 0.025, 0.037, 0.001 and 0.001 respectively). There was statistically significant difference between PC and MG as regards to uterine artery abnormality and persistent notch. There was no statistically significant difference between both groups as regards to placental volume. ROC results revealed that umbilical artery RI, uterine RI, and placental volume cutoff values were higher than 0.67, 0.56, and 43 and the area under the ROC curve was equal to 0.672, 0.851 and 0.527. The sensitivity values of umbilical artery RI, uterine RI, and placental volume were 83.0, 86.5 and 79.2 respectively and the specificity values were 73.3, 60.0 and 62.5 respectively.

Conclusion: Three-dimensional Doppler ultrasound results, as well as resistance index from umbilical artery and uterine artery pulsatility index, resistance index, abnormality and persistent notch, could be considered as tools to determine hemodynamic repercussion caused by preeclampsia.

Keywords: Value of 3-D USS, Placental Volume, Uterine and Umbilical Artery Doppler, Pre-eclampsia.

INTRODUCTION

     Pre-eclampsia (PE) is defined as a new onset of hypertension and proteinuria during pregnancy, after 20 weeks of gestation. It occurs in about 3–5 % of pregnancies and causes substantial maternal and neonatal morbidity and mortality (Minire et al., 2013). Pre-eclampsia is thought to be caused by multiple factors, including placental ischemia, endothelial cell dysfunction, vasospasm, inflammation, improper angiogenesis and oxidative stress (Alves et al., 2018).

     Many investigators believe that the placenta is the trigger for endothelial cell injury. Placental hypoperfusion or ischemia in preeclampsia has many causes. Preexisting vascular disorders such as hypertension and connective tissue disorders can result in poor placental circulation (O’Brien et al., 2013).

     The ultrasonography is a non-invasive method that allows the study of several placental parameters since its formation. Through two-dimensional ultrasonography, the placenta can be assessed according to thickness and maturity (Nagpal et al., 2018). The three-dimensional ultrasonography (3DUS) is one of the most recent technological advances in diagnostic medicine (Pomorski et al., 2012).

     One of the applications of 3DUS is related to the vascularization assessment of organs and structures through three-dimensional power Doppler (3DPD) (Pomorski et al., 2012). The 3D power Doppler allows the assessment of the architecture of the placental tree. Such information is very important considering that problems on the normal development of the placenta (Hata et al., 2011).

     The shallow placentation noted in preeclampsia is a result of the inability of trophoblasts to invade the decidual vessels this invasion of the decidual arterioles is incomplete. The invasive cytotrophoblasts fail to replace tunica media, resulting in mostly intact arterioles that are capable of vasoconstriction. An abnormally elevated impedance to blood flow in the umbilical artery is an indirect reflection of placental pathology (Linask et al., 2014).

     Currently, it is possible to assess women's risk to develop pre-eclampsia by performing uterine artery Doppler both in 1st and 2nd trimesters to investigate impaired trophoblastic invasion within spiral artery and hence impaired uterine flow (Scandiuzzi et al., 2016).

     Determination of placental size is a part of overall assessment of intra-uterine environment. 3-D USS measurement of placental volume is a reliable index in cases of pre-eclampsia (Soongsatitanon and Phupong, 2019). In isolation, this form of screening is felt to be the most accurate as it can predict 81% of women with early onset pre-eclampsia (Thangaratinam et al., 2011).

     This study was conducted to evaluate the placental volume changes using 3-D USS as well as abnormalities in uterine and umbilical artery Doppler indices in prediction of pre-eclampsia.

PATIENTS AND METHODS

     This study was conducted in Department of Obstetrics and Gynecology of Al- Hussein Hospital Al-Azhar University during the periods May 2016 till April 2017. This a prospective observational study carried on two hundred pregnant women enrolled into two equal groups.

Group "A" consisted of 50 primipara and 50 multipara women with known risk factor to develop pre-eclampsia like previous history or medical disorder such as chronic hypertension.

Group "B" consisted of 50 primipara and 50 multipara women without any risk factor to develop pre-eclampsia.

Exclusion Criteria: Congenital fetal anomalies, presence of any other medical disorder with pregnancy and congenital placental or umbilical artery abnormalities.

     Cases were subjected to 3-D USS to measure placental volume from 18-20 weeks in addition to uterine artery and umbilical artery Doppler.

     These parameters repeated on a four-week basis until 34 weeks. The abnormality in Doppler and 3-D USS results were analyzed to detect its sensitivity in predicting occurrence of pre-eclampsia.

     Pre-eclampsia was diagnosed if B.P equals or more than 140/90 detected in pregnant women after 20 weeks' gestation with appropriate cuff and supine position in at least two occasions 6 hours apart and random proteinuria equals or more than +1.

     All participating women underwent: History in details, physical examination, measuring of albumin level in urine and 3DPD ultrasound examination.

     Ultrasounds were done for all cases including fetal biometry, placental morphology assessment and 3D Doppler ultrasound for uterine and umbilical artery. Each patient had a 3D power Doppler ultrasound exam. Automatic volume acquisition of the most vascular area of the placenta was obtained. The Virtual Organ Computer-aided Analysis (VOCAL) imaging was activated and histogram program was used to calculate vascularization index (VI), flow index (FI) and vascularization flow index (VFI) for all cases. Six steps measurements by the manual scanning around the area of interest and fastest scan quality. The same steps were done for all controls.

     Upon participation or admission women were reminded of the study and written consents were obtained.

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. Quantitative data were described using mean and standard deviation Comparisons between groups for categorical variables were assessed using Chi-square test. Student t-test was used to compare two groups. Friedman test was used to compare between more than two periods. Significance of the obtained results was judged at the 5% level. Receiver operating curve (ROC) was used to determine the cutoff values of Umbilical Artery RI, Uterine RI, and Middle cerebral RI as predictors of PE.

RESULTS

     There was no statistically significant difference between both groups as regards maternal age, BMI and gestational age at birth. Group A showed that 36% of PG and 26% of MG developed PIH, while group B showed that 4% of PG and 2% of MG with statistically significant difference between both groups (Table 1).

Table (1):   Comparison between both group as regard to demographic data and PIH

Qualitative data were described using number and percent and was compared using Chi square test while quantitative data was expressed in mean ± SD

p: p value for Student t-test for comparing between PG and MG in each group

p1: p value for Student t-test for comparing between group A (PG + MG) and group B (PG + MG)

     Group A showed that 45% of patients have history of PE, 21% chronic HTN, 8% D.M, 4% kidney diseases, 16% obesity and 6% have other risk factors for PE (Table 2).

Table (2):   Comparison between both groups as regard to risk factors of PE

     There was no statistically significant difference between both groups as regard to umbilical artery PI, while Umbilical Artery RI and abnormality have higher statistically significant values in group A. No significant difference was found between different periods in each group (Table 3).

Table (3):   Comparison between both groups as regards umbilical artery Doppler

Qualitative data were described using number and percent and was compared using Chi square test while quantitative data was expressed in mean ± SD

p: p value for Student t-test for comparing between PG and MG in each group

p1: p value for Student t-test for comparing between group A (PG + MG) and group B (PG + MG)

p2: p value for Friedman test for comparing between different periods in each group

     There was statistically significant difference between groups as regard to uterine artery PI, RI, abnormality and persistent notch (p value= 0.025, 0.037, 0.001 and 0.001 respectively). Also, there is no statistically significant difference between PC and MG as regard to uterine artery abnormality and persistent notch.

   No significant difference was found between different periods in each group (Table 4).

Table (4):   Comparison between both groups as regard to uterine artery Doppler

Qualitative data were described using number and percent and was compared using Chi square test while quantitative data was expressed in mean ± SD

p: p value for Student t-test for comparing between PG and MG in each group

p1: p value for Student t-test for comparing between group A (PG + MG) and group B (PG + MG)

p2: p value for Friedman test for comparing between different periods in each group

     There was no statistically significant difference between both groups as regards placental volume (Table 5). No significant difference was found between different periods in each group.

Table (5):   Comparison between both groups as regard to placental volume (Mean+SD)

Data was expressed in mean ± SD

p: p value for Student t-test for comparing between PG and MG in each group

p1: p value for Student t-test for comparing between group A (PG + MG) and group B (PG + MG)

p2: p value for Friedman test for comparing between different periods in each group

     Our ROC results revealed that Umbilical Artery RI, Uterine RI, and Placental volume cutoff values are higher than 0.67, 0.56, and 43 and the area under the ROC curve is equal to 0.672, 0.851 and 0.527. The sensitivity values of Umbilical Artery RI, Uterine RI, and Placental volume were 83.0, 86.5 and 79.2 respectively and the specificity values were 73.3, 60.0 and 62.5 respectively (Table 6 and Fig. 1).

Table (6):   Umbilical Artery RI, Uterine RI and Placental volume as predictors of PE

AUC: Area Under a Curve p value: Probability value CI: Confidence Intervals

Figure (1):  ROC curve of Umbilical Artery RI, Uterine RI and placental volume

DISCUSSION

     In the present study, mean maternal age in primipara and multipara women with known risk factor to develop pre-eclampsia was 25.41±4.28 and 29.17±4.15 years respectively. While mean maternal age in primipara and multipara women without any risk factor to develop pre-eclampsia which was 23.25±2.38 and 30.11±5.19 years respectively, but with no noted statistically significant differences between both groups as regard maternal age. Furthermore, there was no statistically significant difference both groups as regard to BMI and gestational age at birth.

     Hashish et al. (2015) conducted a prospective case control study including women with singleton pregnancies. Mean of age in Normal group was 26.8 ± 6.4 and High-risk group was 28.7 ± 5.8 with no statistically significant difference between both groups. Also, they did not find any statistically difference between groups as regard BMIs.

     Adil et al. (2018) carried out a prospective observational study to evaluate the role of three dimensional power Doppler ultrasonography (3D PDUS) of the uteroplacental circulation in early pregnancy as a screening tool for prediction of preeclampsia. They reported that there is no statistically significant difference between pregnant females who developed preeclampsia and others who did not regarding age, BMI and gestational age.

     Group A in our study showed that 45% of patients have history of PE, 21% chronic HTN, 8% D.M, 4% kidney diseases, 16% obesity and 6% have other risk factors for PE. Our study revealed 36% of PG and 26% of MG in Group A developed PIH, while group B showed that 4% of PG and 2% of MG with highly statistically significant difference between both groups.

     Magee et al. (2014) reported that the incidence is higher in women with a history of preeclampsia, multiple gestations, chronic hypertension, and underlying renal disease. In addition, obesity, diabetes, thrombophilia, and age older than 40 years are risk factors that put a woman at an increased risk of developing preeclampsia.

     Our study demonstrated there was no statistically significant difference between both groups as regards umbilical artery PI, while umbilical Artery RI and abnormality have highly statistically significant values in group A. The mean umbilical PI of pregnant women without PE was lower than the mean umbilical PI of women that developed PE. Furthermore, pregnant women who did not develop PE had lower mean umbilical RI than in women who developed PE RI. There was a statistically significant difference between groups as regard to uterine artery PI, RI, abnormality and persistent notch. In addition, there was a statistically significant difference between PC and MG as regard to uterine artery abnormality and persistent notch.

     In corroborate to our results, de Almeida et al. (2014) published a prospective case-control study, Placental volumes and vascularity were evaluated by 3-dimensional sonographic, 3-dimensional power Doppler histographic, and 2-dimensional color Doppler studies. Pregnant women were classified as normotensive or hypertensive and stratified by the nature of their hypertensive disorders. There was no statistical difference between these groups with regard to the PI in the umbilical arteries. However, a higher PI in both right and left uterine arteries was observed in hypertensive patients.

     Also, Adekanmi et al. (2019) conducted a longitudinal cohort study, high-risk singleton pregnant women enroled between had uterine and umbilical artery Doppler sonography at 22–24 weeks and 32–34 weeks gestation.

     The mean umbilical PI of pregnant women without PE was significantly lower than the mean umbilical PI of women that developed PE. Furthermore, pregnant women who did not develop PE had lower mean umbilical RI than in women who developed PE RI (Adekanmi et al., 2019).

     Hashish et al. (2015) they stated that uterine artery RI and PI are significantly higher in the study group. Uterine artery PI is negatively correlated with placental volume and vascularization indices.

     Mallikarjunappa et al. (2013) reported a significant association of preeclampsia and abnormalities of Doppler velocity waveforms in the umbilical, the uterine, and the middle cerebral arteries. This was also corroborated by Adekanmi et al. (2019).

     The most frequently studied vessel to predict PE through Doppler US was the uterine artery, being representative of the condition of maternal vascular obstetric circulation. Some authors only focused on the uterine arteries to predict pregnancy complications. Harrington et al. reported results from a cross-sectional study of 191 pregnant women followed up at 24 weeks of gestation through analysis of Doppler US of uterine arteries waveforms (notching). The authors found abnormal uterine Doppler findings (including uni‑ or bilateral notching) in 110 (57.6%) patients. They concluded that there is a clear link between high-resistance uterine waveforms (RI) and an increase in adverse outcomes of pregnancy, including preeclampsia. Papageorghiou and Leslie (2010) confirmed that those with increased mean PI have a six‑fold rise likelihood of serious pregnancy complications.

     Regarding to placental volume; we found that there was no statistically significant difference between both groups as regard to placental volume. They found that PE was seen in 7.7%, GH in 9.0% and SGA in 8.0%. Placental volume was not significantly different between the pregnancies with adverse outcomes and those without.

     Similarly, de Almeida et al. (2014) reported that placental volumes were not statistically different among the different groups. However, patients with superimposed preeclampsia had a significantly lower placental volume-to-estimated fetal weight ratio than normotensive pregnant women.

     The performance of these tests was also compared using areas under receiver operator curves (AUC); Receiver operating curve (ROC) was used to determine the cutoff values of Umbilical Artery RI, Uterine RI, and Placental volume as predictors of PE. Our ROC results revealed that umbilical artery RI, uterine RI, and placental volume cutoff values were higher than 0.67, 0.56, and 43 and the area under the ROC curve was equal to 0.672, 0.851 and 0.527. The sensitivity values of Umbilical Artery RI, Uterine RI, and Placental volume were 83.0, 86.5 and 79.2 respectively and the specificity values were 73.3, 60.0 and 62.5 respectively.

     Lopez-Mendez et al. (2013) reported that the general Doppler result had the most representative values with specificity and PPV of 75.7% and 78.6%, respectively. The sensitivity and the NPV for the general US examination were calculated in 50.8% and 46.7%, respectively.

     The results of current study were also similar to those obtained by Odibo et al. (2011) who stated that the ROC curve for the prediction of PE was 0.71, 0.69 and 0.70 for VI, FI and VFI, respectively.

     Dhakar and Naz (2017) reported that in umbilical artery Doppler sensitivity for all indices i.e. S/D ratio, RI and combined parameters were same. In umbilical artery Doppler RI had specificity of 93.68% and PPV of 25% and combination of parameters had specificity of 91.58% and PPV of 20%. NPV of all the indices was found to be in range of 96-97%. Thus, out of parameters of umbilical artery Doppler S/D ratio is considered to be best indicator.

CONCLUSION

     Three-dimensional Doppler US result, as well as RI from umbilical artery, and uterine artery PI, RI, abnormality and persistent notch, may be considered as tools to determine hemodynamic repercussion caused by PE. Early recognition of women of preeclampsia can help in identifying high risk women who may benefit from early prophylaxis and enhanced surveillance.

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