|Year : 2020 | Volume
| Issue : 3 | Page : 966-971
First-trimester uterine artery Doppler in the prediction of later pregnancy complication
Adel M Elwakel, Sameh M Azab, Amira M Elbakry
Department of Diagnostic Radiology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia Governorate, Egypt
|Date of Submission||17-Dec-2018|
|Date of Decision||12-Feb-2019|
|Date of Acceptance||16-Feb-2019|
|Date of Web Publication||30-Sep-2020|
Amira M Elbakry
Department of Diagnostic Radiology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia Governorate
Source of Support: None, Conflict of Interest: None
The objective of this study was to highlight the role of first-trimester uterine artery Doppler in the prediction of later pregnancy complication.
Hypertensive disorders represent the second most common cause of maternal death, affecting 5–10% of pregnancies worldwide. Pre-eclampsia is believed to develop from inadequate trophoblast invasion of the maternal spiral arteries. Doppler imaging permits noninvasive evaluation of the uteroplacental circulation and is invaluable in the management of high-risk pregnancies.
Patients and methods
Convenience sampling allowed for the recruitment of 120 patients (11–14 weeks gestation) who attended the obstetric outpatient clinic and department at Menoufia University Hospital between March 2017 and April 2018. A complete record of 103 participants was available for the final analysis. Seventeen women were later excluded for the following reasons: four pregnancies miscarried, one pregnancy was complicated by intrauterine fetal death and, finally, 12 (10%) women did not give birth in our departments and were thus lost at follow-up.
The results of this study revealed that six (6%) participants developed pre-eclampsia [four (66.6%) cases of the six patients had a pulsatility index value above the 95th centile, whereas two (33.4%) cases had pulsatility index values above the 50th centile].
Uterine artery Doppler is promising. An ultrasound screening program in high-risk pregnant women would offer clinicians the opportunity to prevent the disease before it manifests clinically.
Keywords: high-risk pregnancy, pre-eclampsia, pulsatility index, uterine artery Doppler, uterine artery notching
|How to cite this article:|
Elwakel AM, Azab SM, Elbakry AM. First-trimester uterine artery Doppler in the prediction of later pregnancy complication. Menoufia Med J 2020;33:966-71
|How to cite this URL:|
Elwakel AM, Azab SM, Elbakry AM. First-trimester uterine artery Doppler in the prediction of later pregnancy complication. Menoufia Med J [serial online] 2020 [cited 2020 Nov 24];33:966-71. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/966/296687
| Introduction|| |
A key aim of antenatal care is to focus on early identification of risks, thereby allowing early commencement of management strategies to minimize the risk of adverse pregnancy outcomes . Hypertensive disorders represent the second most common cause of maternal death, affecting 5–10% of all pregnancies worldwide . Normal placentation is achieved through successful trophoblast invasion of the maternal decidua and myometrium via the dilated spiral arteries. In the process, a low-resistance vascular bed with high blood flow is created . Physiological changes during pregnancy convert the spiral arteries from small muscular arteries to dilated uteroplacental vessels, which are able to accommodate the hemodynamic forces of pregnancy . Unsuccessful trophoblast invasion, with consequent underperfusion of the placenta, leads to the release of hormones into the maternal circulation, which is believed to be the underlying mechanism for the development of pre-eclampsia . Doppler ultrasound is an invaluable tool in the management of high-risk pregnancies. Direct assessment of trophoblast invasion in human pregnancy is not possible; however, the use of Doppler imaging permits noninvasive evaluation of the uteroplacental circulation by comparing systolic and diastolic waveforms ,. In recent years, the question whether uterine artery (UA) spectral Doppler analysis could be used as a screening tool to predict pre-eclampsia before the clinical onset of the disease has thus been asked. In previous studies, the clinical value of UA Doppler has been promising  in the prediction of severe adverse outcomes in patients at high risk for pre-eclampsia . There is evidence to support the belief that trophoblast invasion is maximal in the first trimester  and that pre-eclampsia, deriving from a relative failure of this event, validates Doppler evaluation of the UA from the first trimester of pregnancy . This screening test, performed as an adjunct to routine ultrasound examinations, does not involve significant extra costs and can identify a cohort of patients who will benefit most from increased surveillance during pregnancy .
The aim of this research was to document our experience in demonstrating the sensitivity of UA spectral Doppler screening in the prediction of pre-eclampsia.
| Patients and Methods|| |
This study was approved by the ethical committee of the Faculty of Medicine, Menoufia University. All patients gave written informed consent before inclusion into the study after full explanation of the benefits of the procedure. This study is an observational cross-sectional study conducted in Menoufia University Hospital between March 2017 and April 2018. A total of 103 pregnant women were included who fulfilled the following inclusion criteria: primigravida, single viable intrauterine pregnancy (confirmed by ultrasound), and gestational age at time of inclusion between 11 and 14 weeks (assessed by sure date of the last menstrual period and confirmed by ultrasound). In all, 17 women were later excluded for the following reasons: multiple pregnancies, pre-existing maternal diseases such as renal diseases and diabetes, intrauterine fetal death, fetal anomalies, and pelvic pathology, for example, uterine fibroid. Their ages ranged from 22 to 34 years, with a mean age of 24.78 ± 2.51 years, and they were primigravida. All examinations were carried out between 11 and 14 weeks' of gestation. All cases had undergone preliminary transabdominal/transvaginal pelvic ultrasound on ultrasound machine Philips 11-XD (Philips, Amsterdam, Netherlands) using 3.5–5-MHz abdominal convex probe and 4.6–8 MHz for the transvaginal one. The transabdominal approach is the preferred method, as it is less invasive with good interobserver reproducibility.
Transabdominal ultrasound technique
A 3.5–5-MHz curvilinear transabdominal transducer is used. A midsagittal section of the uterus and cervical canal is obtained, and the transducer is moved laterally until the paracervical vessels are visualized. Color-flow Doppler is applied. The uterine arteries are seen as aliasing vessels along the side of the cervix. Using pulsed wave Doppler, flow velocity waveforms (FVW) from the ascending branch of the UA at the point closest to the internal orifice are obtained, with the Doppler sampling gate set at 2 mm. Care is taken to use the smallest angle of insonation (<30°) to achieve the highest systolic and end-diastolic velocities. When three similar consecutive waveforms are obtained, the pulsatility index (PI) can be measured. The mean PI is calculated as the average reading from each side combined [Figure 1]. Another site for Doppler insonation of the UA is at the level of its apparent cross over with the external iliac artery. Using this method, the probe is positioned ∼2–3 cm inside the iliac crests and then directed toward the pelvis and the lateral side of the uterus. Color-flow Doppler is used to identify each UA. Pulsed wave Doppler is applied ∼1 cm above the point at which the UA crosses over the external iliac artery. This ensures that Doppler velocities are obtained from the main UA trunk .
|Figure 1: Transabdominal Doppler interrogation of the uterine artery at the level of the internal cervical orifice. Abnormal uterine artery waveform demonstrating raised pulsatility index (2.5) with an early diastolic notch.|
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Transvaginal ultrasound technique
A 4.6–8-MHz transvaginal transducer is used. The transducer is placed in the anterior vaginal fornix, and a sagittal section of the cervix is obtained. The vaginal probe is then moved laterally until the paracervical vascular plexus is seen. Color-flow Doppler is applied, and the UA is identified at the level of the cervicocorporeal junction. Measurements are taken at this point before the UA branches into the arcuate arteries. [Figure 2] provides an example of the transvaginal UA FVW.
|Figure 2: Transvaginal Doppler interrogation of the uterine artery at the cervicocorporeal junction. Normal uterine artery waveforms.|
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In our ultrasound Doppler interpretation, in the nonpregnant state and in early pregnancy, Doppler interrogation of the UA typically demonstrates low end-diastolic velocities and an early diastolic notch. Resistance to blood flow within the uteroplacental circulation is transmitted upstream to the uterine arteries and can be measured as an increased PI or resistance index (RI). UA PI values are affected by ethnicity and are lower in women with a high BMI. Our research has determined reference ranges for UA Doppler parameters from 11 to 14 weeks' gestation to 41 weeks' gestation in various populations. UA PI and RI values decrease with increasing gestational age, a change that is thought to be secondary to a fall in impedance in uterine vessels following trophoblastic invasion . In our study, the normal value of UA PI range ranged from 0.9 to 1.75, and UA RI value did not exceed 0.7. 'Notching' appears to be a common feature of the UA Doppler waveform in pregnancy, as it is present in 46–64% of normal gestations in the first trimester. In pregnancies after 20 weeks, a diastolic notch has been defined as a fall of at least 50 cm/s from the maximum diastolic velocity . Similar to UA PI, the prevalence of notching decreases with increasing gestational age until 25 weeks' gestation and thereafter remains stable. Early diastolic notching in the UA represents reduced diastolic velocities compared with those in later diastole and reflects vessel elasticity ,. Persistent early diastolic notching is thought to reflect abnormal maternal vascular tone, whereas defective placentation results in persistently raised UA impedance . Overall, notching demonstrates a low positive predictive value for pre-eclampsia and FGR, in contrast to its 97% negative predictive value for these conditions in a high-risk study population. The poor reproducibility of UA notching has led to its omission from recent research in this field, with a trend instead toward inclusion of more objective measures of vascular impedance, favoring PI. As the formula for the calculation of the PI includes the area below the waveform [(peak systolic − end-diastolic velocity)/mean velocity], the PI indirectly includes the presence or absence of an early diastolic notch.
| Results|| |
The study involved 120 apparently normal pregnant women. They were examined during the first trimester with 2D ultrasonography and then followed up until delivery. A total of 17 women were later excluded for the following reasons: four pregnancies miscarried, one pregnancy was complicated by intrauterine fetal death and, finally, 12 (10%) women did not give birth in our departments and were thus lost at follow-up. Complete outcome data were obtained in 103 consecutive singleton pregnancies. Six cases developed pre-eclampsia, and the prevalence was 6% [Figure 1]. For the purpose of this study, the predictor variable was defined as the Doppler ultrasound examination, the dependent variables as the UA PI and notching, whereas the development of PET was defined as the outcome variable. These are influenced by maternal age, BMI, parity, previous history of PET and gestational weeks at the time of delivery and are the independent variables. (i) Predisposing factors: of the six (6%) patients who developed pre-eclampsia: the majority (57%) were in their teens or 20s, whereas two (29%) were between the ages of 30 and 34, and one (14%) was of advanced maternal age (>35). A single participant had a previous pregnancy complicated by hypertension (16%), three (50%) had no previous complications, whereas two (33%) were primigravidas. (ii) PI values: in our study, first-trimester PI values ranged between 0.9 and 1.75 [Figure 2] and therefore one case was above the 95th centile (PI = 2.5) [Figure 1], as suggested by Gomez et al. . Two had a PI value of 1.5 or above. In the second trimester, only one of the six patients had a PI value above the 95th centile, measuring 2.25, whereas, in an additional two cases, a PI value above the 50th centile was measured. In the third trimester, four (66.6%) of the six patients had a PI value above the 95th centile, whereas two (33.4%) cases had PI values above the 50th centile [Table 1]. The cases that developed pre-eclampsia show that a cutoff value of UA mean PI of more than 1.95 for predicting pre-eclampsia gives a sensitivity value of 66.7% and specificity value of 98.9% [Figure 3], [Table 2] and [Table 3]. (iii) UA notching: three of the six patients who developed pre-eclampsia had UA notching in the first and second trimesters [Figure 1], and two of the six in the third trimester. The outcome for one patient was not available due to the fact that she delivered at 29 weeks gestation.
|Table 1: The relation between the uterine arteries' Doppler and the occurrence of pre-eclampsia among the study population (n=103)|
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|Figure 3: Uterine artery mean pulsatility index receiver operating characteristic (ROC) curve in predicting pre-eclampsia (predicting pre-eclampsia gives sensitivity value of 66.7% and specificity value of 98.9%).|
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|Table 2: Screening characteristics of uterine artery mean pulsatility index for predicting pre-eclampsia|
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|Table 3: Reference intervals for mean uterine artery pulsatility index |
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| Discussion|| |
UA Doppler ultrasound examination has become a valuable method for indirectly assessing uteroplacental circulation from early gestation and has been considered as a potential screening tool for the development of pre-eclampsia, fetal growth restriction (FGR), placental abruption and stillbirth . This study has been conducted to assess the efficacy of UA Doppler at 11–14 weeks of gestation in predicting pre-eclampsia, enabling further earlier prevention and therapeutic interventions to improve maternal and neonatal health. All pregnancies were followed up to termination of pregnancy, and investigated for the development of pre-eclampsia. The PI was used as the study Doppler parameter for the UA. There was no significant difference (P > 0.05) between both groups of normal and abnormal Doppler uterine arteries as regards their age, BMI and the anemic status [Table 4].
|Table 4: The relation between the age, the BMI, anemic status and the Doppler parameter (pulsatility index) of the uterine arteries among the study population (n=103)|
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In pregnancies complicated by pre-eclampsia and/or intrauterine growth restriction, the transformation of these vessels is incomplete. As regards the mean PI of uterine arteries, the results in this study revealed that women who subsequently developed pre-eclampsia demonstrated a significant elevated PI compared with those who did not develop pre-eclampsia (P < 0.001) [Table 2]. This finding was parallel to van-den Elzen et al.  who found that UA PI values were in the highest quartile in women who developed pre-eclampsia, whereas in women who did not develop pre-eclampsia, the PI values were in the lowest quartile.
Two studies done by Harrington et al.  and Gomez et al.  on women at 12–16 weeks & at 11–14 weeks respectively using uterine Doppler and both found that 2.2% developed PE and Pilalis et al.  studied pregnant women under routine prenatal ultrasound examination at 11–14 weeks, and they reported increased impedance to flow in the waveforms obtained by Doppler ultrasound examination of the uterine arteries and significant elevated PI in pregnancies that developed pre-eclampsia. This may be explained as pre-eclampsia and intrauterine growth restriction that are associated with failure of trophoblastic invasion of spiral arteries, and Doppler studies, in these conditions, have shown that impedance to flow in the uterine arteries is increased.
This study revealed a significant difference (P < 0.001) between both groups of normal and abnormal Doppler of uterine arteries as regards the occurrence of pre-eclampsia [Table 1]. Abnormal UA Doppler index was defined as a PI of 95th centile or higher for gestation. As regards the screening characteristics of the UA mean PI for predicting pre-eclampsia, the results in this study revealed that the sensitivity for predicting pre-eclampsia of the UA mean PI more than 1.95 was 66.7% and the specificity was 98.9% [Table 2], values higher than those reported in the previous study of UA Doppler performed at 11–14 weeks of gestation by Gomez et al.  who reported a sensitivity of 25% for the prediction of pre-eclampsia. A possible explanation for the discrepancy between the results is the inclusion criteria in this study that was limited to nulliparous pregnancies in which the prevalence of pre-eclampsia is higher. However, their study was a preliminary study in a low-risk population. Moreover, in this study, the value of UA PI sensitivity is still lower than late second-trimester screening performed by Albaiges et al. . In their study, women with singleton pregnancies who attended routine ultrasonography at 23 weeks had color-Doppler UA imaging. Bilateral UA notches were noted, and left and right UA PIs were measured. A mean PI of more than 1.45 was considered increased.
Screening characteristics for predicting pre-eclampsia and delivery of small-for-gestational-age infants were calculated. Of 1757 pregnancies, increased PI was present in 89 (5.1%), and bilateral notches were noted in 77 (4.4%). Twenty-three (35.3%) of 65 women [95% confidence interval (CI): 23.9–48.2) had increased PI and later developed pre-eclampsia, and eight (80%) of 10 (95% CI: 44.4–97.5) with pre-eclampsia required delivery before 34 weeks. The respective values for women with bilateral notches were 21 (32.3%) of 65 (95% CI: 21.2–45.1) and eight (80%) of 10 (95% CI: 44.4–97.5). The sensitivity of increased PI was 30 (21%) of 143 (95% CI: 14.6–28.6) for delivery of an infant with birth weight below the 10th percentile and seven (70%) of 10 (95% CI: 34.8–93.3) for birth weight below the 10th percentile delivered before 34 weeks. The respective values for bilateral notches were 19 (13.3%) of 143 (95% CI: 8.2–20) and five (50%) of 10 (95% CI: 18.7–81.3). In the study performed by Papageorghiou et al. , Doppler examination of the uterine arteries was attempted in 8335 consecutive singleton pregnancies, satisfactory waveforms were obtained from both vessels in 8202 (98.4%) cases and complete outcome data were available in 7851 (95.7%) of these. The mean gestational age was 23 (range: 22–24) weeks. The mean UA PI did not change significantly with gestation. The median value was 1.04, and the 95th centile was1.63. In 9.3% of cases, early diastolic notches in the waveform from both uterine arteries were present, and, in an additional 11.1% of cases, there were notches unilaterally. Pre-eclampsia with FGR occurred in 42 (0.5%) cases, pre-eclampsia without FGR occurred in 71 (0.9%) and FGR without pre-eclampsia occurred in 698 (8.9%). The sensitivity of increased PI above the 95th centile (1.63) for pre-eclampsia with FGR was 69%. The lower value of UA PI sensitivity in this study may be attributed to what is explained by Plasencia et al.  who stated that, in the majority of normal pregnancies presenting with high UA PI in the first trimester, there is normalization in impedance to flow with advancing gestation, presumably owing to progressive physiological trophoblastic invasion. In contrast, in those pregnancies destined to develop pre-eclampsia owing to impaired trophoblastic invasion, the PI remains high. Consequently, assessment of the rate of change in PI improves the performance of screening and can be used in the follow-up of cases presenting with a high PI at the 11–14 weeks' scan.
A recent meta-analysis by Velauthar et al.  reviewed the accuracy of UA Doppler analysis in the first trimester in the prediction of FGR and pre-eclampsia. Eighteen studies involving 55 974 women were evaluated, with 15 of these studies enrolling women with low-risk pregnancies. UA RI or PI of at least 90th centile and the presence of notching (unilateral/bilateral) were used to define abnormal FVW. There were only two studies evaluating the role of UA notching, and therefore pooling estimates for prediction of pre-eclampsia were not feasible for this variable. An abnormal UA PI in the first trimester was predictive of pre-eclampsia and early-onset pre-eclampsia with sensitivities of 26.4 and 47.8%, respectively. FGR was predicted at 15.4%, whereas early-onset FGR was associated with a higher sensitivity of 39.2%. The sensitivity achieved for placental abruption was 44.4%. First-trimester Doppler indices showed a low predictive accuracy for stillbirth, with a sensitivity of 14.5%. This meta-analysis demonstrated that screening for adverse pregnancy outcome with first-trimester UA Doppler analysis was comparable to screening based on maternal risk factors alone. Although the studies that evaluated early-onset disease were performed in women who were deemed as having low-risk pregnancy, the authors did not find any significant change in the estimates for secondary outcomes with notching or for any adverse composite outcome with waveform abnormalities after inclusion of studies in high-risk women.
| Conclusion|| |
The results of this study concluded that Doppler ultrasound is a reliable, noninvasive method of examining uteroplacental perfusion. Abnormal UA Doppler ultrasonography (elevated PI) in 11–14 weeks' gestation can predict pre-eclampsia. It is recommended to follow-up cases presenting with a high PI at the 11–14 weeks' scan. An ultrasound screening program in pregnant women who are at high risk of developing PET would offer clinicians the opportunity to pre-empt the disease before it manifests clinically by initiating treatment from the first trimester. For further confirmation of the above results, we need to study a larger number of pregnant women and their grouping into high-risk and low-risk ones.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]