Background: Hypertensive disorder in pregnancy are one of the major cause of maternal mortality and morbidity especially in developing countries. It complicates 5-10 % of all pregnancies. Maternal mortality due to hypertensive disorders is reported to be around 10%, more over half of these are preventable. Hypertensive disorder of pregnancy is a sign of underlying pathology which may appear for the first time during pregnancy. Numerous etiology alone or in combination have been suggested to be responsible, they are vascular remodeling of feto-maternal interface, excessive immune response to paternal antigen, systemic inflammatory response and dysfunctional placental or endothelial response; all of these processing being modulated by genetic and environmental parameters Methods: A prospective observational study in which 240 normotensive, pregnant women selected between the gestational age of 14 to 20 weeks attending the ANC clinics, irrespective of parity. Pregnant women with essential hypertension, multiple pregnancy, gestational trophoblastic diseases and associated systemic disease like heart disease, diabetes mellitus and renal disease were excluded from the study. Arterial Doppler of both uterine artery was done. All patients were kept in the regular ANC follow up till the delivery at regular interval for the development of sign and symptoms of hypertension. The patient develop new onset hypertension in pregnancy was noted. Result: Using uterine artery Doppler study is significantly useful in early prediction of hypertensive disorder having sensitivity and specificity of parameters- PI 77.4%and 81.5%, RI as 67.7% and 67.4% and SD ratio as 69.4% and 81.5% respectively. Conclusion: Abnormal uterine artery Doppler studies at 14-20 weeks may be associated with subsequent adverse outcomes. Among the Doppler parameters (PI, RI, S/D) PI is the most sensitive indicator. It can be a useful screening tool for early prediction of hypertensive disorders and the associated perinatal morbidity such as small for gestational age, preterm delivery and IUD.
Hypertensive disorder in pregnancy are one of the major cause of maternal mortality and morbidity especially in developing countries. It complicates 5-10 % of all pregnancies1. Maternal mortality due to hypertensive disorders is reported to be around 10%2, more over half of these are preventable3.Hypertensive disorder of pregnancy is a sign of underlying pathology which may appear for the first time during pregnancy. Numerous etiology alone or in combination have been suggested to be responsible, they are vascular remodeling of feto-maternal interface, excessive immune response to paternal antigen, systemic inflammatory response and dysfunctional placental or endothelial response; all of these processing being modulated by genetic and environmental parameters.
Normally during the first 12 weeks of pregnancy cytotrophoblast invade the spiral arterial walls in the deciduas and replace the endothelium and muscular media
With matrix of cytotrophoblasts and fibrinoid and fibrous tissue4,5. The fibrinoid material is a complex of maternal fibrin and other plasma constituents plus proteinaceous material derived from the trophoblastic cells. Beginning at about 12 weeks of gestation and continue throughout the remainder of the 2ndtrimester, the endovascular trophoblast move in to the myometrial segments of spiral arteries. Once again the trophoblast replaces the endothelium and establishes themselves in the muscular media. The elastic and muscular tissue of myometrium segments of the spiral arteries is gradually lost and replaced by fibrinoid material. This condition, along with increase in blood flow and the associated hemodynamic forces convert the entire length of spiral arteries from small muscular arteries to dilated, tortuous uteroplacental vessels.6
Classically it is held that second wave of endovascular trophoblastic invasion that proceeds in myometrial segments of the spiral arteries from about 15 weeks, if it does not occurs in patients who will develop fetal growth restriction or pre-eclampsia.Lack of physiological conversion is not only apparent in the myometrial segments of spiral arteries, but also in the decidual parts of some of the vessels, so that a proportion of spiral arteries completely fail to undergo trophoblastic invasion and physiological changes. Since unconverted vessels retain high resistance/low capacitance properties, the effect on maternal blood supply to the placenta may be dramatically low. These may manifest as impaired growth of baby or high blood pressure with proteinuria and its complication.
These changes lead us that Uterine artery doppler flow velocity waveform can be used as a predictor test. It is a non invassive test can be used indirectly to assess trophoblast development and uteroplacental flow. Uterine artery Doppler waveform analysis has the potential to predict pregnancy complications associated with uteroplacental insufficiency before the onset of clinical features. Resistance to blood flow within the uteroplacental circulation is transmitted upstream to the uterine arteries. Faulty trophoblastic invasion of the spiral arteries results in diminished placental perfusion and upstream increased uterine artery resistance, this results in an increased pulsatility index (PI) or resistance index (RI) and an early diastolic notch7.
The early identification of clinical problem and effective management plays a significant role in the prevention of the adverse effecton mother and fetus.
Association between parameters of uterine artery doppler and hypertensive disorder of pregnancy has been investigated in several study. However the result are mixed and period of gestation are different. Thus this study was designed to evaluate the role of uterine artery doppler parameter changes as a predictor of hypertensive disorder in pregnancy for early diagnosis and treatment to improve maternal and fetal outcome.
This a Prospective observational study was conducted in the Department of Obstetrics and Gynaecology, Deen Dayal Upadhyay hospital, New Delhi, India for duration of one and half year from August 2017 to January 2019. Ethical clearance was taken from institutional ethical committee.
Study was conducted in 240 Pregnant women of 14 to 20 weeks of gestation who were attending the ANC clinic, from August 2017 in DDU hospital New Delhi were included in the study.
Inclusion criteria
Exclusion criteria
Doppler procedure: Trans-abdominal uterine artery Doppler was done using curvilinear probe (3.5MHz) by locating the uterine artery at utero-cervical junction where it appears to cross the exernal iliac artery. Doppler parameters RI,PI and S/D ratio was analysed.
Methodology
Gestational age was calculated from reliable menstrual history or early ultrasonographical measurements of fetal crown-rump length.
In Doppler study following parameter was assessed;
Statistical analysis
The results are presented in frequencies, percentages and mean±SD. The Chi-square test was used to compare categorical variables. The Unpaired t-test was used to compare continuous variables. The receiving operating curve (ROC) analysis was carried out to find the cutoff value of PI, RI and S/D ratio in predicting hypertension. The area under the curve (AUC) with its 95% confidence interval (CI) was calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy with its 95% CI was calculated. The p-value<0.05 was considered significant. All the analysis was carried out on SPSS 16.0 version (Chicago, Inc., USA).
Table-1: Comparison between abnormal and normal Doppler with development of hypertensive
Hypertensive Disorder |
Abnormal Doppler |
Normal doppler |
p-value1 |
||
No. |
% |
No. |
% |
||
Present |
44 |
35.8 |
18 |
15.4 |
0.001* |
Absent |
79 |
64.2 |
99 |
80.5 |
|
Total |
123 |
100.0 |
117 |
100.0 |
|
1Chi-square test, *Significant
Table 1 shows the comparison between abnormal and normal Doppler findings with development of hypertension among the women enrolled in study. 35.8 % of women with abnormal Doppler finding further developed hypertensive disorder. 64.2% of women did not develop hypertensive disorder even after abnormal Doppler finding. 15.4% of women with normal Doppler finding developed hypertensive disorder. The association of Doppler changes with the development of hypertension was significant (p-value-0.001)
Table-2: Distribution of type of hypertensive disorder developed in women enrolled in study
Type of Hypertensive disorder |
No.(n=62) |
% |
Pre-eclampsia |
23 |
37.1 |
Eclampsia |
9 |
14.5 |
Severe preeclampsia |
7 |
11.3 |
GHTN |
23 |
37.1 |
Table-2 shows the distribution of type of hypertensive disorder developed in women enrolled in study. Pre-eclampsia and GHTN was in 37.1% and 37.1% of women respectively. Eclampsia and Severe preeclampsia was in 14.5% and 11.3% of women respectively.
Table-3: Comparison of predictive values of PI in predicting hypertensive disorder among the women enrolled in study
PI cutoff |
Hypertension developed |
Hypertension not developed |
Total |
|||
No. |
% |
No. |
% |
No. |
% |
|
>0.85 |
48 |
20.0 |
33 |
13.8 |
81 |
33.8 |
≤0.85 |
14 |
5.8 |
145 |
60.4 |
159 |
66.2 |
Total |
62 |
25.8 |
178 |
74.2 |
240 |
100.0 |
Predictive values, % (95%CI) |
|
|
|
|
|
|
Sensitivity |
77.4 (67.0-87.8) |
|||||
Specificity |
81.5 (75.8-87.2) |
|||||
PPV |
59.3 (48.6-70.0) |
|||||
NPV |
91.2 (96.8-95.6) |
|||||
AUC |
0.80 (0.73-0.87) |
1Chi-square test
Table-3 shows the comparison of predictive values of PI in predicting hypertensive disorder among the women enrolled in study. The cutoff value of PI>0.85 had correctly predicted HTN in 20% of women with Sensitivity and Specificity of 77.4% and 81.5% respectively.
Table-4: Comparison of predictive values of RI in predicting hypertensive disorder among the women enrolled in study
RI cutoff |
Hypertension developed |
Hypertension not developed |
Total |
|||
No. |
% |
No. |
% |
No. |
% |
|
>0.50 |
42 |
17.5 |
58 |
24.2 |
100 |
41.7 |
≤0.50 |
20 |
8.3 |
120 |
50.0 |
140 |
58.3 |
Total |
62 |
25.8 |
178 |
74.2 |
240 |
100.0 |
Predictive values, % (95%CI) |
|
|
|
|
|
|
Sensitivity |
67.7 (56.1-79.4) |
|||||
Specificity |
67.4 (60.5-74.3) |
|||||
PPV |
42.0 (32.3-51.7) |
|||||
NPV |
85.7 (79.9-91.5) |
|||||
AUC |
0.71 (0.62-0.79) |
Percentages is from total no. of cases
Table-4 shows the comparison of predictive values of RI in predicting hypertensive disorder among the women enrolled in study. The cutoff value of PI>0.50 had correctly predicted HTN in 17.5% of women with Sensitivity and Specificity of 67.7% and 67.4% respectively.
Table-5: Comparison of predictive values of S/D ratio in predicting hypertensive disorder among the women enrolled in study
SD ratio cutoff |
Hypertension developed |
Hypertension not developed |
Total |
|||
No. |
% |
No. |
% |
No. |
% |
|
>1.50 |
43 |
17.9 |
33 |
13.8 |
76 |
31.7 |
≤1.50 |
19 |
7.9 |
145 |
60.4 |
164 |
68.3 |
Total |
62 |
25.8 |
178 |
74.2 |
240 |
100.0 |
Predictive values, % (95%CI) |
|
|
|
|
|
|
Sensitivity |
69.4 (57.9-80.8) |
|||||
Specificity |
81.5 (75.8-87.2) |
|||||
PPV |
56.6 (45.4-67.7) |
|||||
NPV |
88.4 (83.5-93.3) |
|||||
AUC |
0.83 (0.76-0.89) |
Percentages is from total no. of cases
Table-5 shows the comparison of predictive values of S/D ratio in predicting hypertensive disorder among the women enrolled in study. The cutoff value of S/D ratio>1.50 had correctly predicted HTN in 17.9% of women with Sensitivity and Specificity of 69.4% and 81.5% respectively.
Table 6: Relation of Doppler changes with development of hypertension and mode of delivery
|
No. of patients |
No. of women with hypertensive disorder |
No. with PTVD |
%age of PTVD |
PI>0.85 |
81 |
23 |
12 |
52.17% |
RI>0.50 |
100 |
10 |
8 |
80% |
S/D ratio>1.50 |
76 |
11 |
8 |
72.72% |
Fetomaternalmedicine work with a sole purpose of delivering healthy new born without any compromise on maternal and fetal health. Before the ultrasound era the prediction of hypertensive disorder was done by various maternal assessment and biochemical tests but advent of ultrasound has further improved the challenges faced.
The period 14-20 weeks was chosen to perform the uterine Doppler evaluation because the routine scan for nuchal translucency and early second trimester anatomical assessment was already scheduled at this time of gestation in our population and placental implantation is completed by 14-18 weeks8.
The study of Polatet al9(2015)showed significant hemodynamic changes in uterine artery Doppler assessment during the 14 to 20 weeks of gestation; these hemodynamic changes were evident during the second trimester likely reflecting a time correlation between the intervillous circulation and marked changes in the umbilical and fetal circulations at this time of pregnancy. At this stage they supposed that transabdominal uterine examination may have technical problems because the uterus is not large enough and the full bladder technique is necessary to perform the Doppler examination. Consequently, the distended bladder may cause an alteration in blood flow in small arteries. By using the transvaginal route, the probe is located closer to the uterine artery, the angle of insonation is usually closer to zero degree and the wave forms obtained have better definition10.
In present study out of 240, 62 women (25.8%) developed hypertensive disorder among them 37.1% developed pre-eclampsia and GHTN and 14.5% and 11.3% developed eclampsia and severe pre-eclampsia respectively. This finding is almost in agreement with the study of Chyadet al11(2018) they enrolled 33 primigravida women in the study. 30.3% among them developed pre-eclampsia. In the study conducted by Sahoo K et al12 that enrolled 220 women at 14- 20 week of gestation who underwent uterine artery Doppler .He observed that 54 women (24.54%) developed hypertensive disorder during follow up.
In present study out of 240 women 123 had abnormal Doppler (51.2%) in which 44 women developed hypertensive disorder (35.8 %). 64.2% of women did not develop hypertensive disorder even after abnormal Doppler finding. 15.4% of women with normal Doppler finding developed hypertensive disorder. The association of Doppler changes with the development of hypertension was significant(p-value-0.001). In contrast of study conducted by K sahoo et al12the uterine artery Doppler done in 220 pregnant women at 14-20 weeks. Abnormal Doppler results were found in 45.9% of women at which 65% women developed hypertensive disorder. This discrepancy may be due to different Doppler parameter and their cutoff .as they have not included S/D in study. only PI and RI was included. Morever study group included only primigravida women and primigravida itself had increased risk of hypertensive disorders.
In the present study, the cutoff value of PI>0.85 had correctly predicted HTN in 20% of women with Sensitivity and Specificity of 77.4% and 81.5% respectively. In this study, the cutoff value of RI>0.50 had correctly predicted HTN in 17.5% of women with Sensitivity and Specificity of 67.7% and 67.4% respectively. The finding of this study in detecting the HTN by PI and RI is similar to other studies. Chakraborty and Saharan13 (2017) reported that using uterine artery Doppler Study in combination is significantly useful in early prediction of PIH having specificity and sensitivity of Uterine artery Doppler study – PI Index as 91.67% and 85.71 %, RI Index as 87.5% and 71.43% and diastolic notch as 94.44% and 92.85 % respectively. K Sahooet al12conducted a study among 220 primigravida women, uterine artery PI and RI included. In this study sensitivity and specifity of PI and RI was 44.44%, 89.75% and 77.8%, 85.5% respectively. Abidoyeet al14 (2017) also found that for the hypertensive disorders of pregnancy group, resistivity index > 0.66 had a sensitivity of 50.0%, specificity of 69.1%.
Table 7: - Comparison of sensitivity and specificity of PI in various study
PI |
Sensitivity |
Specificity |
Chakraborty et al13 |
91.67% |
85.71% |
K. sahoo et al12 |
44.44% |
89.75% |
Chyad et al11 |
60% |
87% |
Narang et al15 |
75.9% |
69.4% |
Present study |
77.4% |
81.5% |
Narang et al15(2016) showed that uterine artery Doppler pulsatility index (PI) at 11-14 weeks of pregnancy was found to be a good screening method (sensitivity-75.9%, specificity-79.6%) for prediction of preeclampsia.
Chyad et al11 recently conducted a study to find out the role of uterine artery Doppler at 14-20 week of gestation as a predictor of PIH among 33 women. 10 women(30.3%) developed hypertensive disorder. For the prediction Doppler indices PI and RI were included and when RI was used sensitivity and specificity were 90%, 87% and when PI was used sensitivity and specificity were 60%, 87% and concluded that RI was better indicator.
Table 8:- Comparison of sensitivity and specificity of RI in various study
RI |
Sensitivity |
Specificity |
Chakraborty et al13 |
87.5% |
71.43% |
K Sahoo et al12 |
77.8% |
85.5% |
Kaytri S16 |
40.74% |
96.29% |
Abidoye at el14 |
50% |
69.1% |
Chyad et al11 |
90% |
87% |
Present study |
67.7% |
67.4% |
In the present study, the cutoff value of S/D ratio>1.50 had correctly predicted HTN in 17.9% of women with Sensitivity and Specificity of 69.4% and 81.5% respectively. Sensitivity of uterine artery S/D ratio was only 12.5% for predicting hypertensive disorder in study done by Nagar T et al17 which is lower than the present study. This may be contributed to a relative small sample size(240 vs 500) and narrow inclusion criteria of present study as compared to the study done by Nagar T et al17.
Table 9:- Comparison of sensitivity and specificity of S/D in various study
S/D Ratio |
Sensitivity |
Specificity |
PPV |
NPV |
Nagar T et al17 |
12.5% |
91.3% |
11.11% |
92.31% |
Present study |
69.4% |
81.5% |
56.6% |
88.4% |
In the present study out of 240 women 13(5.4%) women underwent preterm vaginal delivery among these 12 women had abnormal doppler finding. There was significant association between abnormal Doppler parameter and PTVD. Similer result found in study conducted by OlufemiAdebariOloyedeet al18 among 430 women and uterine artery Doppler was done. Out of 430 patient 24 women (5.5%) underwent to PTVD.
Abnormal uterine artery Doppler studies at 14-20 weeks may be associated with subsequent adverse outcomes. Among the Doppler parameters (PI, RI, S/D) PI is the most sensitive indicator. It can be a useful screening tool for hypertensive disorders and the associated perinatal morbidity such as small for gestational age, preterm delivery and IUD. Nevertheless, to do interventions in order to prevent adverse outcomes based on abnormal Doppler results .So, uterine artery Doppler to be done routinely with the second trimester scan to improve maternal and perinatal outcome.