Uterine artery Doppler at 11-14 weeks of gestation in the prediction of preeclampsia: An observational study

Abstract

BACKGROUND

Pre-eclampsia is a significant challenge in obstetric care and adversely affects the feto-maternal outcomes, causing significant perinatal morbidity and mortality. Early detection of women at higher risk of developing pre-eclampsia in the first trimester provides a vital opportunity to initiate timely prophylactic therapies. First-trimester uterine artery Doppler is gaining prominence as a promising tool in early risk stratification.

AIM

To assess the role of uterine artery Doppler in screening for pre-eclampsia at 11-14 weeks of gestation.

METHODS

Pregnant women attending routine antenatal care between 11 weeks and 14 weeks of gestation and undergoing first-trimester nuchal translucency screening were offered enrolment in the study. After calculating gestational age from the last menstrual period or fetal biometry (crown-rump length), Doppler ultrasound of bilateral uterine arteries was performed, and relevant Doppler parameters were recorded. Patients were followed until delivery for development of preeclampsia.

RESULTS

Out of a total of 342 participants, 42 women (12.28%) developed preeclampsia, while the remaining 300 women (87.71%) had a normal pregnancy without preeclampsia. The mean uterine artery pulsatility index was significantly elevated in the pre-eclampsia group (1.9455 ± 0.36) compared to the normal group (1.474 ± 0.52) (P < 0.001). Using a pulsatility index threshold of 1.622, the receiver operating characteristic curve analysis demonstrated a sensitivity of 75% (95% confidence internal: 0.66-0.82), specificity of 86% (95% confidence internal: 0.78-0.91), positive predictive value of 84.27%, and negative predictive value of 77.48% with a diagnostic accuracy of 80.5%. The area under the curve was 0.896, indicating good diagnostic performance. Uterine artery notching was observed in 88% of the pre-eclampsia group compared to 16% in the control group, a difference that was statistically significant (P < 0.001).

CONCLUSION

Uterine artery Doppler in the first trimester at 11-14 weeks of gestation showed a good diagnostic value for forecasting the development of pre-eclampsia and holds promise as a valuable tool for early risk stratification.

Key Words: Pre-eclampsia; Uterine artery Doppler; First trimester; Pulsatility index; Resistive index; Diastolic notch

Core Tip: In this observational study, we examined the role of uterine artery Doppler assessment in the first trimester between 11 weeks and 14 weeks of gestation in predicting the development of preeclampsia. Our findings suggest that abnormal uterine artery Doppler parameters at 11-14 weeks of gestation are significantly associated with an elevated risk of developing preeclampsia later in pregnancy. Using receiver operating characteristic curve analysis, we demonstrate that, at specific cut-off values for the pulsatility index and resistive index, uterine artery Doppler shows good discriminatory power in predicting the future risk of preeclampsia.

INTRODUCTION

Pre-eclampsia poses a significant challenge in obstetric care and contributes substantially to adverse maternal and fetal outcomes. It is a multisystem disorder characterized by the new onset of hypertension and proteinuria, or other signs of end-organ dysfunction, occurring after 20 weeks of gestation[1-3]. Pre-eclampsia complicates an estimated 2%-8% of pregnancies with a bearing on both maternal and fetal outcomes. According to estimates, preeclampsia claims the lives of approximately 76000 pregnant women and 500000 children annually worldwide[4]. Pre-eclampsia leads to both immediate (impaired coagulation and hepatorenal functions) and long-term (cardiovascular, respiratory and neurological) adverse effects on pregnant women. The pathogenesis of pre-eclampsia is considered a two-stage process[1]. In stage I, an intricate interaction between genetic factors (like FMS-related receptor tyrosine kinase 1 single-nucleotide polymorphism), immunological factors (like T-cell imbalance) and maternal factors (like antiphospholipid antibodies) results in impaired trophoblast invasion (shallow placentation). Due to shallow placentation there is impaired placental perfusion, which results in oxidative stress, which in turn leads to the production of cytokines, angiogenic factors, and angiotensin 1 autoantibodies that cause vascular endothelial dysfunction, which leads to the onset of clinical symptoms[5]. The pathogenesis of pre-eclampsia begins in the first trimester of pregnancy, which provides a window of opportunity for early detection of high-risk individuals and prevention of the development of pre-eclampsia[4].

Primary prevention remains the most effective approach to managing pre-eclampsia, as treatment choices are scarce once clinical symptoms manifest, delivery often being the only definitive solution[5,6]. Therefore, early identification of women at high risk is essential for mitigating the impact of this condition[7-9]. There is level A scientific evidence supporting the use of low-dose aspirin, initiated in the first trimester before 16 weeks (optimally at 12 weeks), to prevent the onset or reduce the severity of pre-eclampsia[10,11]. These findings have led to the development of recommendations by the international Federation of Gynecology and Obstetrics and the American College of Obstetricians and Gynecologists, advocating for first-trimester screening for preeclampsia and the use of aspirin in high-risk patients[12,13]. Thus, it is crucial to develop and employ reliable predictive tools in the first trimester to identify high-risk patients and institute timely and targeted prophylactic intervention. First-trimester uterine artery Doppler has shown promise in forecasting the emergence of pre-eclampsia[14]. The abnormalities in the placental vascular bed that lead to the development of pre-eclampsia start very early in the first trimester, well before the manifestation of clinical symptoms[15]. Uterine artery Doppler imaging by detecting high-resistance blood flow can provide indirect indication about the underlying defective placentation, which is the key pathological mechanism in the genesis of pre-eclampsia[14].

Prior research has established the role of uterine artery Doppler in the second trimester in predicting the likelihood of developing pre-eclampsia. A high resistance blood flow in uterine arteries at 22-24 weeks’ gestation is estimated to increase the risk of developing pre-eclampsia by six times[15,16]. A growing body of evidence is accumulating favoring the potential utility of first-trimester uterine artery Doppler performed between 11 weeks and 14 weeks of gestation for early risk assessment and prediction of developing pre-eclampsia[17]. The predictive value of first-trimester uterine artery Doppler is enhanced when it is combined with maternal clinical and biochemical indicators such as mean arterial pressure and biochemical markers like placental growth factor and pregnancy-associated plasma protein A[17,18]. The 11-14 weeks gestational period provides an ideal opportunity for uterine artery Doppler assessment, as it coincides with the timing of the nuchal translucency scan that is routinely performed for screening of chromosomal anomalies. This study aims to assess the role of uterine artery Doppler in screening for pre-eclampsia between 11 weeks and 14 weeks of gestation.

MATERIALS AND METHODS

Study design and setting

This observational study was undertaken in the Department of Radiodiagnosis and Imaging at Government Medical College, in collaboration with Lalla Ded Hospital (Srinagar, India), over a period of two and a half years from October 2022 to May 2025. The study protocol was approved by the Institutional Ethical Review Committee (Approval No. IRBGMC/RADIO 195).

Study participants

Pregnant women attending for routine antenatal care between 11 weeks and 14 weeks of gestation and undergoing first-trimester nuchal translucency screening were offered enrolment. A total of 360 women with confirmed single intrauterine live pregnancies were registered subsequent to acquisition of written informed consent. Among these, 4 patients were subsequently excluded from the study (two patients had a history of chronic hypertension, one patient developed systemic lupus erythematosus and one patient had a neural tube defect in the fetus), and 14 patients were lost to follow-up, resulting in a final study population of 342 women.

Women with multi-fetal pregnancy or pre-existing medical disorders like hypertension, renal disease, diabetes mellitus, or connective tissue disease were excluded. Additional exclusion criteria included pregnancies resulting in termination before 20 weeks of gestation, known major fetal anomalies at the time of enrolment or subsequent detection of major fetal anomalies, major maternal structural anomalies like uterine malformations, large fibroids interfering with uterine artery assessment and use of medications known to affect vascular resistance (corticosteroids, aspirin).

Doppler ultrasound examination

Gestational age was calculated on the basis of either the last menstrual period or fetal crown-rump length measurement. Doppler ultrasound scans were performed using a 3.5 MHz convex transducer on LOGIQ P9 ultrasound equipment via a transabdominal window. The Doppler examinations were carried out in compliance with recommendations of the Fetal Medicine Foundation[4]. A single experienced radiologist with more than 10 years of experience in fetal radiology performed all the scans, excluding any potential inter-observer variability. Intra-observer variability was assessed by repeating uterine artery Doppler measurements in a randomly selected subset of 25 participants. The repeat scans were performed by the same sonographer, blinded to the initial results, under identical scanning conditions. The intra-class correlation coefficient for pulsatility index (PI) and resistive index (RI) was calculated, demonstrating excellent intra-observer agreement (intra-class correlation coefficient of 0.92). A midsagittal view of the uterus was first obtained to visualize the cervical canal. The probe was then tilted laterally to identify the paracervical vascular plexus. Color Doppler imaging was activated to locate the uterine artery as it ascended toward the uterine body. Pulsed Doppler was then used to acquire the uterine artery spectral waveform before the vessel branched into arcuate arteries. The spectral waveform was obtained at the level of the internal outer segment using small sampling volumes of 2 mm. Measurements were repeated until at least three concordant waveforms were obtained. The procedure was then subsequently performed on the contralateral side. The angle of insonation was below 60 degrees. PI and RI values were recorded bilaterally. Early diastolic notch, if present, was also recorded.

Follow-up

Participants were followed until delivery. All patients received routine antenatal care according to institutional guidelines. At enrolment, all women underwent a clinical evaluation, nuchal translucency scan and uterine artery Doppler assessment. Standard first-trimester investigations included haemoglobin, blood sugar and thyroid function testing. Routine supplements included daily oral iron (60 mg), folic acid (500 μg) right from the first trimester and calcium supplementation (1000 mg) from the second trimester onwards. Follow-up assessment included a visit at 20 weeks of gestation, followed by biweekly evaluations. Each follow-up included a comprehensive clinical examination with special attention to blood pressure measurement.

Definitions

The diagnosis of pre-eclampsia was based on American College of Obstetricians and Gynecologists criteria: New-onset hypertension [systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg on two occasions at least 4 hours apart after 20 weeks of gestation] along with proteinuria (≥ 1+ on urine dipstick or ≥ 300 mg/24 hours). Severe pre-eclampsia was defined by the presence of one or more of the following. Systolic BP ≥ 160 mmHg or diastolic BP ≥ 110 mmHg, proteinuria ≥ 3+ on dipstick or ≥ 5 g/24 hours, symptoms of end-organ involvement (severe headache, visual disturbances and epigastric pain), lab abnormalities (thrombocytopenia < 100000/mm³, elevated liver enzymes, serum creatinine > 1.1 mg/dL) and fetal growth restriction. Early-onset pre-eclampsia was defined as onset before 34 weeks of gestation, and late-onset pre-eclampsia as the onset of signs and symptoms after 34 weeks. As this was an observational study aimed at finding the role of uterine artery Doppler for predicting pre-eclampsia, no prophylactic medications were given to any patient either at the time of enrolment or based on Doppler findings. Women who developed pre-eclampsia and those who did not were recorded. Those who developed preeclampsia were managed according to standard institutional guidelines. The protocol included close maternal and fetal surveillance with blood pressure monitoring and lab investigations, including urine dipstick for proteinuria, liver and kidney function tests, and platelet counts. Antihypertensives such as labetalol and methyldopa were initiated when indicated.

Statistical analysis

Data were analyzed using SPSS version 24.0. Descriptive statistics, including percentages, means and standard deviations, were computed. Categorical variables were analyzed using the χ² test, whereas continuous variables were analyzed using Welch’s t-tests due to heterogeneous variances between groups, with results reported as mean differences and 95% confidence internal (CI). Receiver operating characteristic (ROC) curves were constructed to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of the Doppler indices.

Logistic regression analysis was done to identify independent risk factors for pre-eclampsia. Since we had a limited number of cases (n = 42), parsimonious multivariate logistic regression analysis was done to avoid over-adjustment. The predictors included mean PI, mean RI and the most relevant clinical confounders [body mass index (BMI) and mean arterial pressure (MAP)] based on previous literature and baseline comparisons. Adjusted odds ratio (OR) with 95%CI and P-value was calculated. A P-value < 0.05 was considered statistically significant. Post-hoc power analysis was done to calculate the statistical power of uterine artery PI.

RESULTS

This observational study was conducted over a span of two and a half years at a tertiary care hospital. A total of 342 pregnant women with a single intrauterine pregnancy were enrolled. The baseline demographic and clinical features of participants in both the pre-eclampsia and control groups are summarized in Table 1. There was no significant difference in the mean age between the pre-eclampsia group and the control group (P > 0.05). Similarly, no statistically significant difference was found in BMI or gestational age between the two groups at the time of enrolment (P > 0.05). The MAP at baseline was significantly elevated in the pre-eclampsia group (94.1 ± 14.3 mmHg) in comparison to the control group (87.9 ± 6.5 mmHg), suggesting an early hemodynamic variation between the groups (P = 0.008). The distribution of gravidity and parity between the pre-eclampsia and control groups is given in Table 2. A significantly larger proportion of women in the pre-eclampsia group were multigravida (gravida 3: 52.4%) in contrast to the control group (26.7%), with a P-value of 0.026, indicating a statistically significant association. This observation implies that increased gravidity may be associated with a higher risk of developing pre-eclampsia. Of the 42 women who developed pre-eclampsia, 18 (42.9%) had early-onset disease and 24 (57.1%) had late-onset disease. Among early-onset cases, 11 were severe and 7 were mild. In the late-onset group, 13 had severe and 11 had mild pre-eclampsia. The highest mean uterine artery PI was observed in early-onset severe cases (2.03 ± 0.01), while the lowest was in late-onset mild cases (1.91 ± 0.02). Bilateral notching was most frequent in early-onset severe cases (81.8%). Early-onset and severe cases were associated with earlier gestational age at diagnosis. The distribution of timing and severity of pre-eclampsia and the respective PI values is illustrated in Table 3. However, there was no significant difference in parity distribution between the two groups (P = 0.0748), as the proportions of nulliparous, primiparous, and multiparous women were relatively similar. These results imply that in our study cohort, gravidity rather than parity was associated with a higher risk of pre-eclampsia.

Table 1 Baseline characteristics of patients, mean ± SD/n (%).

Baseline characteristic	Pre-eclampsia group (n = 42)	Normal group (n = 300)	P value
Age (years)	31.0 ± 5	30.0 ± 5	0.23
Range	28-38	20-40
BMI (kg/m2)	24.29 ± 1.59	23.09 ± 1.87	0.15
GA at enrollment (weeks)	11.43 ± 0.65	11.66 ± 0.67	0.08
Parity
Nulliparous	18 (42.9)	180 (60.0)	0.0751
Primiparous	16 (38.1)	70 (23.3)
Multiparous	8 (19.0)	50 (16.7)
MAP (mmHg)	94.1 ± 14.3	87.9 ± 6.5	0.008a
Range	78-125	77-118

^aP < 0.05.

BMI: Body mass index; GA: Gestational age; MAP: Mean arterial pressure.

Table 2 Distribution of study participants according to gravida and parity status, n (%).

Parameters		Groups		P value
		Pre-eclampsia (n = 42)	Normal (n = 300)
Gravida	1	10 (23.8)	126 (42.0)	0.026
	2	10 (23.8)	94 (31.3)
	3	22 (52.4)	80 (26.7)
Parity	0	18 (42.9)	180 (60.0)	0.0748
	1	16 (38.1)	70 (23.3)
	2	8 (19.0)	50 (16.7)

Table 3 Timing and severity of preeclampsia in relation to uterine artery Doppler findings (n = 42), mean ± SD/n (%).

Parameter	Early-onset severe PE (n = 11)	Early-onset mild PE (n = 7)	Late-onset severe PE (n = 13)	Late-onset mild PE (n = 11)
Total PE cases (%)	26.2	16.7	31.0	26.2
Uterine artery PI	2.03 ± 0.01	1.97 ± 0.01	1.94 ± 0.02	1.91 ± 0.04
Bilateral notching	9 (81.8)	5 (71.4)	8 (61.5)	4 (36.4)
GA at diagnosis (weeks)	29.3 ± 1.4	30.9 ± 1.0	35.8 ± 0.9	36.4 ± 1.1
P value	< 0.001

PE: Pre-eclampsia; PI: Pulsatility index; GA: Gestational age.

The pregnancy outcome of the two groups is summarized in Table 4. Compared to the control group, the pre-eclampsia group had a lower mean gestational age at delivery and a higher incidence of low birth weight. The rate of neonatal intensive care unit admission was significantly higher in the pre-eclampsia group compared to the control group. Uterine artery notching was observed more frequently in the pre-eclampsia group in comparison to the control group (P < 0.001) (Table 5). The PI measured in the right uterine artery was significantly greater in the pre-eclampsia group (1.955 ± 0.35) than in the control group (1.481 ± 0.53), with a P < 0.001. Similarly, the left uterine artery PI was elevated in the pre-eclampsia group (1.936 ± 0.39) compared to the control group (1.467 ± 0.58) (P < 0.001). The mean PI was also significantly greater in the pre-eclampsia group (1.9455 ± 0.36) in contrast to the control group (1.4740 ± 0.52; P < 0.001; Table 6).

Table 4 Pregnancy outcome of the study participants, mean ± SD/n (%).

		Pre-eclampsia group (n = 42)	Normal group (n = 300)	P value
Gestational age at birth (weeks)		34.4 ± 2.0	37.9 ± 1.6	< 0.001a
Mode of delivery	Vaginal	14 (33.3)	198 (66)	< 0.001a
	LSCS	28 (66.7)	102 (34)
Fetal complications	LBW	26 (61.9)	28 (9.3)	< 0.001a
	NICU admission	32 (76.1)	27(9)	< 0.001a
	Meconium-stained liquor	1 (2.3)	4 (1.3)	0.611

^aP < 0.001.

LSCS: Lower segment cesarean section; LBW: Low birth weight; NICU: Neonatal intensive care unit.

Table 5 Uterine artery notching among the study participants, n (%).

Uterine artery notching	Groups		P value
	Pre-eclampsia (n = 42)	Normal (n = 300)
Present	37 (88)	48 (16)	< 0.001a
Unilateral notching	11 (29.7)	32 (66.6)
Bilateral notching	26 (70.3)	16 (33.4)
Absent	5 (12)	252 (84)

^aP < 0.001.

Table 6 Comparison of uterine artery Doppler indices.

Parameter	Preeclampsia (n = 42)	Normal (n = 300)	P value
Right UA-PI	1.955 ± 0.35	1.481 ± 0.53	< 0.001a
Left UA-PI	1.936 ± 0.39	1.467 ± 0.58
Mean PI	1.9455 ± 0.36	1.4740 ± 0.52
Right UA-RI	0.750 ± 0.12	0.551 ± 0.21
Left UA-RI	0.746 ± 0.14	0.516 ± 0.23
Mean RI	0.748 ± 0.13	0.5335 ± 0.22

^aP < 0.001.

UA: Umbilical artery; PI: Pulsatility index; RI: Resistive index.

In addition, RI value measurement for bilateral uterine arteries was significantly elevated in the pre-eclampsia group. The right uterine artery RI measured 0.750 ± 0.12 in the pre-eclampsia group vs 0.551 ± 0.21 in the control group, and the left uterine artery RI was 0.746 ± 0.14 in the pre-eclampsia group compared to 0.516 ± 0.23 in the control group, with both differences reaching statistical significance. The mean RI was also significantly greater in the pre-eclampsia group compared to the control group (all P < 0.001). A multivariate regression model incorporating mean uterine artery PI, RI, BMI and MAP showed RI as an independent risk factor for pre-eclampsia (adjusted OR of 1.47 per 0.1-unit increase; 95%CI: 1.07-2.01; P = 0.016), whereas PI did not remain statistically significant (adjusted OR of 1.07 per unit increase; 95%CI: 0.96-1.20; P = 0.297). In order to explain this discrepancy, a sensitivity analysis was done excluding RI. In this model, PI emerged as a significant predicting factor for pre-eclampsia (adjusted OR of 1.21 per 0.1-unit increase; 95%CI: 1.13-1.29; P < 0.001). This suggests that PI and RI may attenuate each other’s effect when run in the same model (Table 7). This attenuation of PI’s effect is likely attributable to the high degree of correlation between RI and PI, which may have introduced multicollinearity into the model.

Table 7 Sensitivity analysis-model excluding resistive index.

Predictor	Adjusted OR	95%CI	P value
PI (per 0.1 unit)	1.21	1.13-1.29	< 0.001
BMI (per 1 kg/m2)	1.42	1.15-1.74	0.001
MAP (per 1 mmHg)	1.06	1.01-1.10	0.009

PI: Pulsatility index; BMI: Body mass index; MAP: Mean arterial pressure; OR: Odds ratio; CI: Confidence internal.

Both BMI (adjusted OR of 1.43 per kg/m²; 95%CI: 1.16-1.76; P = 0.001) and MAP (adjusted OR of 1.05 per mmHg; 95%CI: 1.01-1.10; P = 0.014) were independently associated with pre-eclampsia (Table 8). The ROC analysis for PI as a predictor of pre-eclampsia is presented in Table 9. The area under the curve is 0.896, indicating high discriminatory power. At a cut-off value of 1.622, the PI achieved a high sensitivity of 75% (95%CI: 0.66-0.82) and specificity of 86% (95%CI: 0.78-0.91). The PPV was 84.27%, and the NPV was 77.48%. The overall diagnostic accuracy was 80.5% (Figure1A). Table 10 shows the ROC analysis for RI as a predictor of pre-eclampsia. The area under the curve is 0.920, indicating excellent diagnostic ability. At a cut-off value of 0.66, the RI demonstrated a sensitivity of 64% and a high specificity of 93%. The PPV was 90.14%, and the NPV was 72.09%. The overall diagnostic accuracy was 78.50% (Figure 1B). Normal and abnormal uterine artery Doppler at 13 weeks of gestation is given in Figure 2. Post-hoc power analysis was done to calculate statistical power and demonstrated robust statistical power (> 90%) for detecting differences in uterine artery Doppler parameters between two groups. This high sensitivity possibly resulted from large effect magnitudes and our study design’s analytical strength, especially the large non-preeclamptic group, which effectively compensated for the smaller number of pre-eclampsia cases.

Figure 1 Diagnostic performance. A: Pulsatility index; B: Resistive index. PI: Pulsatility index; AUC: Area under the curve; RI: Resistive index.

Figure 2 Normal and abnormal uterine artery Doppler at 13 weeks of gestation. A: Uterine artery Doppler waveform in a 13-week pregnant woman with normal pregnancy outcome; B: High pulsatility index in uterine artery with presence of diastolic notching in a 13-week pregnant woman who subsequently developed pre-eclampsia. PS: Peak systolic velocity; ED: End diastolic velocity; TAmax: Time-averaged maximum velocity; PI: Pulsatility index; RI: Resistive index; HR: Heart rate; TAmean: Time-averaged mean velocity.

Table 8 Multivariable logistic regression for prediction of preeclampsia.

Predictor	Adjusted OR	95%CI	P value
PI (per 0.1 unit)	1.07	0.96-1.20	0.001
RI (per 0.1 unit)	1.47	1.07-2.01
BMI (per 1 kg/m2)	1.43	1.16-1.76
MAP (per 1 mmHg)	1.05	1.01-1.10	0.014

Model includes pulsatility index (PI), resistive index (RI), body mass index, and mean arterial pressure; RI and PI rescaled per 0.1-unit increase. Odds ratio for PI and RI rescaled to 0.1 unit increases to improve interpretability. Model adjusted for body mass index and mean arterial pressure. PI: Pulsatility index; RI: Resistive index; BMI: Body mass index; MAP: Mean arterial pressure; OR: Odds ratio; CI: Confidence internal.

Table 9 Receiver operating characteristic analysis for pulsatility index as predictor of pre-eclampsia.

Parameter	Value
AUC	0.896
P value	< 0.001
Cut-off	1.622
95%CI (sensitivity)	0.66-0.82
95%CI (specificity)	0.78-0.91
Sensitivity	75.0%
Specificity	86.0%
PPV	84.27%
NPV	77.48%
Diagnostic accuracy	80.50%

AUC: Area under the curve; CI: Confidence internal; PPV: Positive predictive value; NPV: Negative predictive value.

Table 10 Receiver operating characteristic analysis resistive index as predictor of pre-eclampsia.

Parameter	Value
AUC	0.920
P value	< 0.001
Cut-off	0.66
95%CI (sensitivity)	0.54-0.73
95%CI (specificity)	0.86-0.97
Sensitivity	64.0%
Specificity	93.0%
PPV	90.14%
NPV	72.09%
Diagnostic accuracy	78.50%

AUC: Area under the curve; CI: Confidence internal; PPV: Positive predictive value; NPV: Negative predictive value.

DISCUSSION

Uterine artery Doppler is a non-invasive diagnostic tool used to examine impedance within the placental vascular bed and plays a role in the early prediction of pre-eclampsia in pregnant women. High resistance blood flow in uterine arteries, as indicated by raised PI and RI, is linked with a higher risk of both intrauterine fetal growth restriction and pre-eclampsia. A growing body of evidence has also underscored the potential role of uterine artery Doppler study in the first trimester for risk stratification and early prediction of pre-eclampsia. The findings from the current study highlight that women who subsequently developed pre-eclampsia demonstrated abnormal uterine artery Doppler indices at 11-14 weeks of gestation, which included raised PI and RI and the presence of early diastolic notching. These changes showed a statistically significant association with the future development of pre-eclampsia, thereby reiterating the predictive value of first-trimester uterine artery Doppler screening to facilitate early recognition of pregnancies at high risk that can potentially benefit from watchful monitoring and prophylactic measures. At a cut-off value of 1.622, the PI achieved a sensitivity of 75.0% and specificity of 86.0%, effectively identifying a majority of true cases while minimizing false positives. The PPV was 84.27%, and the NPV was 77.48%. The overall diagnostic accuracy was 80.50%, supporting the use of PI as a reliable non-invasive Doppler parameter in the early identification and risk stratification of pre-eclamptic pregnancies. These results are in concordance with prior research. For example, Rk et al[19] reported high sensitivity (92.9%) and specificity (97.1%), PPV (81.5%), NPV (99%), and a diagnostic accuracy (96.59%) using a mean PI cut-off of 2.27 in the first trimester for predicting pre-eclampsia. Gupta et al[20] also demonstrated the diagnostic utility of uterine artery Doppler, with a sensitivity of 65.4% and a high specificity of 96.7% using a PI cut-off value of 1.71.

A multivariate regression analysis was conducted to determine whether uterine artery Doppler indices were independently associated with the development of preeclampsia, after adjusting for potential confounding variables. In the adjusted model, the RI emerged as a statistically significant predictor, while the PI lost its significance. This attenuation of PI’s effect is likely attributable to the high degree of correlation between RI and PI, which may have introduced multicollinearity into the model. To further explore this, a sensitivity analysis was performed excluding RI from the model. In this analysis, PI demonstrated a strong and statistically significant association with the risk of developing pre-eclampsia. These findings suggest that both RI and PI have independent predictive value for pre-eclampsia, but their simultaneous inclusion in the same regression model may mask the individual effect of each due to their high intercorrelation. Apart from Doppler findings, both maternal BMI and MAP were independently associated with the development of pre-eclampsia in multivariate regression analysis. These findings augment the previous studies which identify obesity and increased early pregnancy blood pressure as independent risk factors for pre-eclampsia.

In the present analysis, at a cut-off value of 0.66, the RI demonstrated a robust diagnostic profile. The area under the ROC curve was 0.920, indicating its excellent discriminative power. At this threshold, the sensitivity was found to be 64.0%, meaning that nearly two-thirds of pre-eclampsia cases were correctly identified. The specificity was high at 93.0%, suggesting strong accuracy in identifying normal pregnancies. The PPV and NPV were 90.14% and 72.09%, respectively, supporting the utility of RI in clinical decision-making, particularly in ruling in disease. The overall diagnostic accuracy was 78.5%, confirming that RI is a reliable parameter in the early prediction of pre-eclampsia. These findings support the incorporation of uterine artery RI assessment in routine antenatal Doppler screening, especially for high-risk pregnancies. However, its moderate sensitivity suggests that it is best used in combination with other clinical and biochemical markers.

These results are in agreement with those of Nagpal et al[21], who reported that combining an RI > 0.65 with uterine artery notching yielded a sensitivity of 82.6% and a specificity of 85.4%. Similarly, Oancea et al[22] concluded that the combination of elevated PI and diastolic notching had moderate predictive accuracy, with a sensitivity of 65.4% and specificity of 66%. Zakaria et al[23] investigated the predictive value of uterine artery Doppler in the first trimester and found that the uterine artery PI was significantly greater in the pre-eclampsia group in contrast to the control group. Using a cut-off value of 1.91 at 11-13 weeks of gestation, they reported a sensitivity of 71.43%, a specificity of 66.98%, and a high NPV of 94.7%. Conversely, Cnossen et al[24], in a meta-analysis encompassing three studies and a total of 4966 Low-risk patients, reported that while first-trimester uterine artery Doppler had a relatively low sensitivity of 25%, it demonstrated a high specificity of 95% in predicting pre-eclampsia. Further, Poon et al[25] concluded that integrating uterine artery Doppler parameters with maternal demographic and clinical characteristics enhanced the predictive sensitivity to 45% for all pre-eclampsia cases and notably up to 80% for early-onset pre-eclampsia.

In another study, Demers et al[26] reported that an elevated first-trimester uterine artery PI was significantly associated with preterm pre-eclampsia, but not with term pre-eclampsia. Combining uterine artery PI with maternal clinical characteristics was able to accurately predict 45% of preterm pre-eclampsia cases, with an acceptable false positive rate of 10%. Mohammed et al[27], in their study using uterine artery Doppler between 11 weeks and 13 weeks of gestation, demonstrated a sensitivity of 77.6% and a specificity of 76.4% at a PI cut-off value of 1.88. Similarly, they observed a sensitivity of 62% and a specificity of 70% at an RI cut-off value of 0.84. Combining Doppler parameters with serum β-human chorionic gonadotropin levels enhanced the diagnostic performance, leading to a 5% increase in both sensitivity and specificity.

The variations in reported PI cut-off values across different studies may stem from inhomogeneity in study populations, such as ethnicity, maternal body habitus and baseline high risk for pre-eclampsia, or variations in gestational age when the screening was performed, as PI naturally decreases with advancing gestation. In addition, the variation in the predictive performance of first-trimester uterine artery Doppler for pre-eclampsia may arise from differences in ultrasound equipment used and ultrasound settings such as resolution and angle of insonation. Lastly, operator-dependent factors, including level of expertise and site of uterine artery sampling, may also affect the reported Doppler indices.

One of the key strengths of the present study is the use of a standardized protocol, which included a single experienced sonographer, the use of a single ultrasound machine, and uniform Doppler assessment techniques. This approach minimized intragroup variability, thereby enhancing the reliability of the measurements and improving our ability to distinguish true group differences from measurement-related variability. Consistent with previous studies, our findings support the utility of first-trimester uterine artery Doppler - performed concurrently with the nuchal translucency scan - as a predictive tool for the development of pre-eclampsia. Importantly, our study contributes valuable data from an Indian cohort, thereby reinforcing the applicability and relevance of uterine artery Doppler in early pregnancy, particularly in resource-limited settings.

Meanwhile, this study still has many limitations. First, a limited sample size with a small number of pre-eclampsia patients restricts the statistical power of the study, thereby affecting the generalizability of the findings. Second, being a single-center study, the results of the present study may have restricted external applicability and may not be representative of wider populations. Third, the lack of extended neonatal follow-up affects the ability to assess long-term outcomes for the newborns born to pre-eclamptic women.

CONCLUSION

In conclusion, this study reinforces the clinical relevance of first-trimester uterine artery Doppler screening in predicting the risk of preeclampsia. The strong association between abnormal Doppler parameters and the subsequent development of pre-eclampsia underscores its potential as a valuable screening modality in antenatal care. Integration of uterine artery Doppler assessment into routine first-trimester screening protocols may enable early risk stratification, allowing for the timely initiation of preventive strategies and enhanced surveillance to improve maternal and fetal outcomes. Furthermore, increased BMI and MAP are independent risk factors for the development of pre-eclampsia in addition to elevated PI and RI. Considering these factors alongside uterine artery Doppler in first-trimester screening models will enable increased risk stratification and targeted preventive measures.