|Year : 2019 | Volume
| Issue : 2 | Page : 106-112
Uterine and umbilical artery doppler in women with pre-eclampsia and their pregnancy outcomes
Ademola Joseph Adekanmi1, Adebola Roberts2, Janet Adetinuke Akinmoladun1, Abiodun Oludotun Adeyinka1
1 Department of Radiology, College of Medicine University of Ibadan, Ibadan, Nigeria
2 Department of Obstetrics and Gynaecology, College of Medicine University of Ibadan, Ibadan, Nigeria
|Date of Web Publication||10-Jun-2019|
Dr. Adebola Roberts
Department of Obstetrics and Gynaecology, College of Medicine, University of Ibadan, Ibadan
Source of Support: None, Conflict of Interest: None
Background: Pre-eclampsia (PE) is an important public health menace in both developed and developing countries with high maternal and perinatal morbidity and mortality globally. A major goal towards improving antenatal management of PE is to develop accurate prediction models that identify women at high risk of this disease for appropriate interventions. Methodology: In a longitudinal cohort study, high-risk singleton pregnant women enroled between April 2015 and February 2016 had uterine and umbilical artery Doppler sonography at 22–24 weeks and 32–34 weeks gestation and had their delivery outcomes documented by the obstetrician and gynaecologist. The peak systolic velocity (PSV), end-diastolic velocity (EDV), Resistivity Index (RI), Pulsatility Index (PI) and the systolic-diastolic ratio (S/D) were recorded. Results: Among the ninety-eight high-risk pregnant women, 61 (62.2%) developed PE and 32 (32.8%) did not have PE. In the PE cases, 15 (24.5%) were mild and 46 (74.5%) were severe PE. The uterine artery PI was significantly associated with PE. A unit increase in uterine PI in high-risk pregnancies, increases the odd of PE by 37.37 times (95% confidence interval; odds ratio = 6.09, 241.9; P < 0.001). The combination of the uterine and umbilical PSV predicted 80.3% of severe PE. All three spontaneous abortions were in women who developed PE, more caesarean section (48.4%) and 69.2% of 45 pre-term deliveries occurred in women with severe PE. Conclusion: The findings from this study show significantly lower uterine and umbilical arteries PSV and EDV but higher RI, PI and S/D in cases that developed PE. The uterine artery PI is the best predictor of PE, whereas the combinations of uterine and umbilical arteries PSV best predict severity of PE among high-risk pregnant Nigeria women.
Keywords: Doppler indices, Doppler ultrasonography, pre-eclampsia, umbilical, uterine
|How to cite this article:|
Adekanmi AJ, Roberts A, Akinmoladun JA, Adeyinka AO. Uterine and umbilical artery doppler in women with pre-eclampsia and their pregnancy outcomes. Niger Postgrad Med J 2019;26:106-12
|How to cite this URL:|
Adekanmi AJ, Roberts A, Akinmoladun JA, Adeyinka AO. Uterine and umbilical artery doppler in women with pre-eclampsia and their pregnancy outcomes. Niger Postgrad Med J [serial online] 2019 [cited 2019 Jul 21];26:106-12. Available from: http://www.npmj.org/text.asp?2019/26/2/106/259909
| Introduction|| |
Pre-eclampsia (PE) remains an important public health menace in both developed and developing countries contributing to maternal and perinatal morbidity and mortality. It complicates about 2%–10% of pregnancies globally,, affecting about ten million women with about 76,000 maternal deaths annually from complications of PE and related hypertensive disorders.
PE, a pregnancy-related hypertensive disorder, seen after 20 weeks of gestation in affected women, is a continuum in pregnancy-induced hypertension (PIH) clinical spectrum. Untreated PE progresses to eclampsia when convulsions occur in addition to hypertension in pregnancy and proteinuria. It is responsible for about 12%–25% of foetal growth restriction, small for gestational age (GA) infants and about 15%–20% of all pre-term births; with severe long-term prematurity-related neonatal morbidity and deaths. Studies have shown variations in the incidence and prevalence of PE.,, The World Health Organisation noted that the incidence of PE is seven times higher in developing countries, where severe PE and eclampsia are more common and seen in 4% of all deliveries in some parts but up to 18% in other parts of Africa. About 10%–25% of these cases result in maternal deaths.
In Nigeria, the incidence of eclampsia, the end of the spectrum of PIH ranges from 0.3 to 9/100 deliveries,, with a rising trend in the incidence over the years. Eclampsia may have a dramatic, abrupt onset and in many women without any warning signs/symptoms.,
A major goal towards improving antenatal management of PE is to develop accurate prediction models that identify women at high risk of disease for early diagnosis and prompt management. However, diagnosing PE remains a challenge due to its highly variable clinical presentation, and the disease often progresses over the course of weeks before diagnosis is confirmed. Recent data suggest that in some women, PE and even eclampsia may develop in the absence of hypertension or proteinuria. Therefore, rather than relying only on the presence of hypertension or proteinuria, the patient history, physical examination, laboratory and imaging studies have been shown to be useful in the diagnosis of PE.
Doppler analysis has emerged as a useful method for prediction of PE and adverse pregnancy outcome,, as the clinical manifestations of PE have been shown to be preceded by evidence of impaired placental perfusion on the Doppler ultrasonography. The Uterine artery blood flow represents the maternal haemodynamic status, and increased uterine artery PI and RI documented to be associated with increased risk of PE., Increased Uterine Pulsatility Index (PI) and Resistance Index (RI) have been associated with an increased risk for PE., Furthermore, the presence of an early diastolic notch in the waveform has been shown in several studies to be associated with adverse outcomes.,, Several studies have also included the umbilical artery as a relevant vessel in the evaluation of PE.,,,, However, there is no complete data about the most frequently altered Doppler parameters in their individual or combined form for each artery. In this study, we, therefore, evaluated the uterine and umbilical arteries changes and pregnancy outcomes in cases that developed PE and those that did not among a cohort of high-risk pregnancy (HRP) women. We also evaluated the Doppler parameters that best predict PE in high-risk native pregnant women in Ibadan, Southwest Nigeria.
| Methodology|| |
In this longitudinal cohort study, we evaluated the uterine and umbilical arteries and pregnancy outcomes in PE cases in HRPs, and using several Doppler ultrasound parameters and their combinations determined Doppler parameters that best predict PE.
Singleton pregnancies registered or referred to the antenatal clinic of the University College Hospital, Ibadan, between April 2015 and February 2016 were recruited by the obstetrician and gynaecologist and trained nursing staff. This study had the approval of the Oyo State, Research Ethical Review Committee, Department of Planning, Research and Statistics, Ministry of Health Oyo State (Approval number AD 13/479/701, November 2014). Participation in this study was completely voluntary and based on written informed consent after explanation of the intents and purpose of the study.
Data from our hospital indicated that indicated 1650 pregnancies are registered in a year and have four wards for the obstetric cases in addition to the labour ward and two wards for the care of newborns and infants. A pilot study showed 4–5 HRP cases present per week, giving a total of 84–130 patients over the 6 months of recruitment of patients. Using the sample size calculation; n = N* X/(X + N– 1) where X = Zα/22° *p*(1-p)/e2 and Zα/2° is 1.96 at confidence level of 95%, α is 0.05, e = significance level (0.05), P is sample proportion and N, the population size. The minimum sample size was therefore 82–98 cases. However, in view of possible non-responders, a total sampling method was adapted for the study to include all consenting high-risk participants recruited during the study period. HRP inclusion criteria include singleton pregnant women with pre-existing hypertension, diabetes mellitus, kidney disease, heart disease, previous intra-uterine growth restriction, elderly primigravidas, previous PE, haemoglobinopathies and human immunodeficiency syndrome. All cases of multiple pregnancies, foetal malformations and unknown last menstrual period without early dating scans were excluded.
A structured data form was used to document the sociodemographic, anthropometric, obstetric parameters and high-risk factors among the studied population.
The ultrasound examination was performed using a GENERAL ELECTRIC LOGIQ P5 ultrasound scanner machine. An initial obstetric ultrasound scan was carried out to document obstetric parameters, number of foetuses to exclude multiple gestation and foetus with malformations. Maternal uterine and foetal umbilical arteries of the participants were evaluated with Doppler ultrasound at second trimester (22–24 weeks) and third trimester (32–34 weeks) periods.
For this study, PE is defined as elevated blood pressure, in pregnancy after 20 weeks GA, ≥140/90 mmHg on two measurement 6 h apart and proteinuria > 30 mg in a 24 h urine sample or at least 1+ in a dipstick random urine sample. Women with PE were further subdivided into mild and severe PE based on systolic blood pressure of 130–160 mmHg, diastolic blood pressure (DBP) >90 mmHg and proteinuria of +1 and >160 mmHg systolic blood pressure with DBP of ≥110 mmHg and/or +3 proteinuria.
Doppler study was carried out with a transabdominal pulsed, curved array 3.5–5.0 MHZ transducer. For the uterine artery investigation, the participants were scanned in a semi-recumbent position with a slight lateral tilt. The transducer was placed longitudinally in the lower lateral quadrant of the abdomen with slight medial angulation. Colour Doppler imaging was applied afterwards to identify the uterine artery as it crosses the external iliac artery. The wall filter was set at 50–60 Hz and the angle of insonation was below 20°. Pulsed wave Doppler with a gate size of 2 mm was placed over it at about 1 cm below the crossover point of the uterine artery and the external iliac artery to generate the spectral wave pattern.
The umbilical artery Doppler was carried out at a free loop of the cord and the velocimetry recorded in the absence of foetal movement or uterine contraction. Both the uterine and umbilical arteries interrogation were carried out in accordance with the technique of Bramham et al., the International Society of Ultrasound in Obstetrics and Gynaecology and Adekanmi et al. reported on normal second and third trimester Doppler parameters. For both the uterine and umbilical arteries spectral waveform analysis, automatic tracing/manual tracing of the waveforms was done to generate the Doppler parameters. The values of three consecutive waveforms were averaged and the mean recorded. The following parameters were recorded: peak systolic velocity (PSV), end-diastolic velocity (EDV), RI, PI and the systolic-diastolic ratio (S/D). Abnormal uterine artery waveform indicators were high RI > 0.58 and early diastolic notch, while abnormal umbilical artery waveform indicators were taken as any of the following: raised PI above two standard deviations (SDs) above the mean for GA, end-diastolic volume reduction, absence of diastolic flow or reversal of end-diastolic wave pattern. The participants were monitored until delivery for assessment of pregnancy outcomes.
Demographic variables were summarised and tabulated. All data were analysed using the IBM SPSS Statistical Package for the social sciences) statistics for windows, version 23.0 (IBM Corp., Armonk, NY: USA) and frequency distributions were generated with appropriate graphs and tables. Qualitative variables were compared using Chi-square test and reported by proportions. Quantitative variables between the two groups were compared using Student's t-test, with level significance set at 0.05. While one-way analysis of variance was used to compare between more than two groups.
| Results|| |
This prospective study was done among 98 pregnant women with HRP, five were lost to follow-up, whereas 93 delivered at our institution. The pregnant women were grouped into two groups: 61 (62.2%) women who developed PE with or without other pregnancy complications and 32 (32.8%) pregnant women who did not develop PE. Among the pregnant women that developed PE, 15 (24.5%) had mild PE and 46 (74.5%) had severe PE. The mean age of pregnant women who developed PE was 32.03 ± 4.11 years with a range of 22–39 years, while the mean age of pregnant women who did not develop PE was 31.65 ± 6.42 years with a range of 15–48. There was no significant difference in the age between the two groups (P = 0.936), other patients' characteristics are as shown in [Table 1].
There was a statistically significant difference in the mean uterine EDV of pregnant women who did not develop PE (M = 34.96 cm/s, SD = 13.44) and that of women who developed PE (M = 25.97 cm/s, SD = 14.01) (P = 0.003). The uterine PSV, however, showed no significant differences. Pregnant women who did not develop PE also had lower mean uterine RI (M = 0.50, SD = 0.14) compared with women who developed PE RI (M = 0.59, SD = 0.13) (P = 0.002). Likewise, the mean uterine PI of pregnant women without PE (M = 0.75, SD = 0.28) was significantly lower than the mean uterine PI of women that developed PE (M = 1.38, SD = 0.67) (P < 0.001). Furthermore, the mean uterine S/D ratio of pregnant women who did not develop PE (M = 1.92, SD = 0.50) was statistically significantly lower than mean uterine S/D ratio of pregnant women who developed PE (M = 2.79, SD = 1.03) (P < 0.001).
The mean umbilical PSV of pregnant women who did not develop PE (M = 45.59 cm/s, SD = 12.03) was significantly higher than that of women who developed PE (M = 38.48 cm/s, SD = 14.16) (P = 0.019). Similarly, there was a statistical significant difference in the mean umbilical EDV between women without PE (M = 20.23 cm/s, SD = 7.67) and pregnant women who developed PE (M = 15.58 cm/s, SD = 8.43) (P = 0.016). The mean umbilical PI of pregnant women without PE (M = 0.88, SD = 0.20) was significantly lower than the mean umbilical PI of women that developed PE (M = 1.14, SD = 0.48) (P = 0.001). Furthermore, pregnant women who did not develop PE had lower mean umbilical RI (M = 0.57, SD = 0.12) than in women who developed PE RI (M = 0.64, SD = 0.14) (P = 0.018). Furthermore, the mean umbilical S/D ratio was significantly lower in women who did not develop PE (M = 2.41, SD = 0.57) than in women who developed PE (M = 2.95, SD = 1.13) (P = 0.020) as shown in [Table 2].
|Table 2: Doppler parameters among non-pre-eclampsia and pre-eclampsia high-risk pregnancy cohort|
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After adjusting for other variables, the uterine artery PI was the only Doppler parameter that was significantly associated with PE. For a unit increase in uterine PI, the odds of PE among women with HRP was 38.37 times more (95% confidence interval [CI]; odds ratio [OR] = 6.09, 241.9; P < 0.001).
Receiver operative curve analysis shows that the uterine PI significantly predicted about 86% of PE correctly (area under the curve [AUC] = 0.862, 95% CI = 0.784, 0.941; P < 0.001) [Figure 1].
|Figure 1: Receiver operative curve of uterine artery Pulsatility Index specificity and sensitivity in predicting pre-eclampsia|
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Severity of pre-eclampsia and Doppler parameters
There was a statistically significant difference in the mean uterine artery PSV of pregnant women who had mild PE (M = 49.58 cm/s, SD = 14.75) and that of women who developed severe PE (M = 62.22 cm/s, SD = 18.89) (P = 0.024). The mean uterine S/D ratio of pregnant women with mild PE (M = 2.30, SD = 0.59) was statistically significantly lower than mean uterine S/D ratio of pregnant women who had severe PE (M = 2.94, SD = 1.03) (P = 0.010).
In the umbilical arteries, the mean umbilical PSV of pregnant women who had mild PE (M = 44.68 cm/s, SD = 14.58) was significantly higher than that of women who developed severe PE (M = 35.77 cm/s, SD = 11.95) (P = 0.046) [Table 3]. Other Doppler parameters; uterine PSV, RI and PI though slightly higher in those with severe PE; slightly higher umbilical RI, PI and S/D, but decreased EDV in severe PE were not statistically significant as shown in [Table 3].
After adjusting for other variables, the combination of the mean uterine PSV and mean umbilical PSV were significantly associated with severity of PE. The odds of severe PE was 1.11 more times for a unit increase in the mean uterine PSV (95% CI OR = 1.02, 1.21; P = 0.018). However, there was a reduced risk of about 8% for a unit increase in umbilical PSV (95% CI OR = 0.856, 0.992; P = 0.030).
The combination of the mean uterine PSV and mean umbilical PSV significantly predicted about 80.3% of severe PE correctly (AUC = 0.803, 95% CI AUC 0.673, 0.934; P =0.002), as shown in [Figure 2].
|Figure 2: Receiver operative curve of uterine and umbilical artery peak systolic volume specificity and sensitivity in predicting pre-eclampsia|
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Concerning deliveries at term, that is 37 completed weeks of gestation, 29 (60.4%) of those without PE had term deliveries when compared to 19 (39.6%) women who developed PE had term deliveries with a P < 0.001. More women with severe PE (45.6%) had operative delivery through caesarean section. All the women who had abortion (3), before GA of 28 weeks, were women with PE.
There were 45 pre-term deliveries recorded in this study, overall 27 (64.3) women with severe PE and 12 (28.6%) in those with mild PE. This was statistically significant with P < 0.001. There was also a statistically significant association between PE and neonatal complications, 27 (62.8%) of low birthweight deliveries were from women with severe PE, mild PE and participant without PE recorded 27.9% and 9.3% (P < 0.001), respectively [Table 4].
|Table 4: Delivery outcomes among the no pre-eclampsia and the pre-eclampsia group|
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| Discussion|| |
Several studies have reported the various proportion of occurrence of PE among high-risk pregnant women. In this study, about 62.2% of women with HRP had PE with or without other complications. Severe PE (72.5%) was more common among women with PE, in agreement with Liu et al.'s findings among 412 Taiwanese with gestational hypertensive disorders; severe PE was seen in 88.3% of the PE cases. In contrast, Lopez-Mendez et al. among 102 hP Mexican women studied, reported severe PE in 41.5% among the PE cases. Likewise, Myatt et al. reported 40.0% of severe PE cases among PE cases studied. However, both studies had a younger PE population compared to the present study. Studies have shown that older age patients may be more at risk of severe PE,, and this, in addition to the fact that PE is more common in developing countries, might account for the high proportion in this study and differences observed. In this study, the systolic blood pressure (P < 0.001) and DBP (P < 0.001) were significantly different in women who had PE with or without other pregnancy complication and those who do not have PE. There was no significant difference in age and between women who had PE and women without PE, at variance with Liu et al. report in which age in addition to systolic and DBP showed significant difference among eclampsia cases and controls. Again this difference may be due to the patient selection criteria of eclampsia cases employed in their study compared with PE cases in this study.
Our observation of decreased blood flow velocities, particularly the EDV but increased impedance indices (RI, PI and S/D) in both the uterine and umbilical arteries in women that developed PE compared with those that did not in agreement with Barati et al.'s documentation of increased diastolic flow velocities in normal pregnancies. While decreased flow velocities and high resistance/impedance indices are seen in PE.
In line with our study, the significantly higher mean uterine artery S/D ratio, RI and PI among PE cases compared to women without PE, support the report by Mallikarjunappa et al. that the uterine and umbilical artery Doppler study showed elevation of these three parameters among pregnant women with PE in the second and third trimester. This was also corroborated by Li et al.'s report. In contrast, Lopez-Mendez et al. observed no significant difference in the uterine arteries' PI and RI, but reported a significant difference in the umbilical artery PI and RI between HRP women with PE and those without PE, which is similar to our findings in the umbilical arteries in the present study. The difference between result in this current study and the study above could be because of differences in population dynamics and the abnormality limits of obstetric Doppler parameters which may differ between populations.
Previous researchers have reported different findings on the Doppler parameter that best predict PE among high-risk patients. These include: second trimester unilateral early diastolic notch, increased PI and the presence of early diastolic notch, and abnormal uterine artery PI values of >1.45 and/or the presence of bilateral diastolic notch. However, Li et al. noted that the diastolic notch is not commonly seen and present only in about 25% of cases in the second trimester. According to Nagar et al., the combination of uterine and umbilical arteries Doppler parameters better predicts PE than uterine artery findings alone. In our evaluation of the various combinations of the uterine and umbilical arteries Doppler parameters that best predict PE in this study, we observed that the uterine artery PI alone best predict PE. The difference in this current study and the systematic review and bivariable meta-analysis of the use of uterine artery Doppler ultrasonography to predict PE and intra-uterine growth restriction by Cnossen et al. could be because of difference in study methodology. The fact that none of the studies considered by Cnoseen et al. was from a native African population, could be a major factor, bearing in mind the fact that the population dynamics and Doppler abnormality limits differ from one population to another. Furthermore, Doppler ultrasound was performed in about 61% of the population in the third trimester in this study compared to 18 and 24 weeks' gestation in most of the studies reviewed by Cnossen et al.
We also observed that the uterine artery PI significantly predict about 86% of PE cases correctly in this study (AUC = 0.862, 95% CI 0.784). This is slightly higher than the figures reported by Spencer et al. and Plasencia et al., in which the uterine artery mean PI in the second trimester correctly predicts about 79% and 67% of all cases of PE, respectively. Furthermore, Doppler assessment is reported to be more useful in severe PE than the mild form and the impedance indices are said to show greater changes in severe PE., Myatt et al. also reported a significant relationship between severity of PE and the uterine notch and PI. Although the PSV and E$DV were not included in the Doppler parameters tested as predictors of severe PE by afore mentioned authors. When we considered all the Doppler parameters, there was a significant increase in the mean uterine PSV and S/D ratio (impedance index) with severity of PE, this suggests that the elevated uterine artery PSV results from the high resistance in the uteroplacental circulation in severe PE, whereas the umbilical arteries showed significantly reduced PSV among pregnant women with severe PE in comparison with those with mild PE. This may suggest that these Doppler parameters are of more diagnostic value in the evaluation of severity of PE among native pregnant Nigerian women. The combination of the mean uterine artery PSV and the mean umbilical artery PSV best predict severity of PE among pregnant women with PE in this study. Although the mean uterine artery PI was increased among patients with severe PE, it was not statistically significant (P = 0.061).
In addition, the observation that pre-term delivery and low birth weight babies among high-risk pregnant women in this study were significantly associated with PE and severity of PE is consistent with reports from other parts of the world. Further studies with larger sample size of mild and severe PE cases to determine the effect of Doppler indices on the severity of PE are suggested in the future.
| Conclusion|| |
The findings from this study show that the PSV and EDV were significantly lower, whereas the RI, PI and S/D were significantly higher in cases that developed PE. The uterine artery PI is the best predictor of PE. A combination of the uterine artery PSV and the umbilical artery PSV best predict severity of PE among pregnant women with PE among native Nigeria women; these parameters shoul, therefore, be evaluated in high-risk patient for PE.
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Conflicts of interest
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]