Predictive value of second-trimester ophthalmic artery Doppler for identifying women at risk for preeclampsia

Abstract

BACKGROUND

Preeclampsia (PE) is a multifactorial hypertensive disorder specific to pregnancy that significantly contributes to maternal and perinatal morbidity and mortality worldwide. According to hospital-based studies, its prevalence in India ranges from 5% to 15%. Despite advances in obstetric care, the early identification of women at risk remains a major clinical challenge. Ophthalmic artery Doppler (OAD), a noninvasive and reproducible imaging technique, provides important information on cerebral autoregulation and maternal vascular resistance with potential exploratory utility in the early detection of PE.

AIM

To evaluate the predictive value of maternal OAD indices measured during the second trimester (17–23 weeks of gestation) for the subsequent development of PE in a cohort of initially normotensive pregnant women.

METHODS

This prospective observational study, conducted from March 2024 to February 2025, enrolled 90 antenatal women in their second trimester with no prior history of hypertension or renal disease. OAD evaluation was performed using the transorbital approach with the Alpinion E-CUBE 8 ultrasound system, and key Doppler indices were recorded. Participants were subsequently followed through the third trimester to assess the development of PE. Statistical analysis was performed using the independent samples t-test for continuous variables, Fisher’s exact test for categorical variables, and receiver operating characteristic curve analysis to assess the predictive performance of Doppler parameters.

RESULTS

Out of the 90 participants, 8 (8.89%) developed PE during follow-up. The resistive index (P = 0.004), pulsatility index (P = 0.0003), and most notably, the peak ratio (PR) (P < 0.0001) showed statistically significant differences between the normotensive and preeclamptic groups. Among the Doppler parameters, PR demonstrated the best diagnostic performance, with a diagnostic accuracy of 91.11%, sensitivity of 100%, specificity of 90.24%, and area under the receiver operating characteristic curve of 0.90. Elevated PR values were strongly associated with the subsequent development of PE, indicating potential predictive value that requires further validation in larger studies.

CONCLUSION

Maternal OAD measurements, particularly PR, demonstrated significant associations with the subsequent development of PE in this study cohort. Its noninvasive nature, ease of application, and observed diagnostic performance suggest that it may warrant further evaluation as an adjunctive risk stratification tool in antenatal screening protocols, particularly in resource-limited settings. The early detection and management of high-risk pregnancies could be greatly improved by incorporating OAD into standard obstetric care, potentially improving maternal and perinatal outcomes.

Key Words: Preeclampsia; Ophthalmic artery Doppler; Peak ratio; Pulsatility index; Resistive index; Maternal cerebral hemodynamics; Antenatal screening

Core Tip: Preeclampsia is a leading cause of maternal and neonatal morbidity in India, with a prevalence of 5%–15%. The ophthalmic artery reflects cerebral hemodynamic changes during pregnancy, and ophthalmic artery Doppler offers a noninvasive method to assess maternal vascular resistance. In this prospective study, transorbital ophthalmic artery Doppler was performed to assess 90 normotensive antenatal women during the second trimester. Doppler parameters were recorded, and participants were followed through the third trimester to monitor the subsequent development of preeclampsia.

INTRODUCTION

Hypertensive disorders represent a significant challenge in obstetric care, complicating approximately 12%–22% of all pregnancies, with preeclampsia (PE) being the most common, affecting up to 10% of pregnancies globally[1]. In India, hospital-based data indicate that the prevalence of PE ranges between 5% and 15%, while eclampsia, a severe manifestation involving seizures, accounts for roughly 1.5% of cases[2]. According to the World Health Organization, eclampsia contributes to nearly 12% of maternal deaths in low- and middle-income countries, highlighting its substantial impact on maternal health[3].

PE generally develops after 20 weeks of gestation and is characterized by new-onset hypertension (blood pressure ≥ 140/90 mmHg on two separate readings obtained at least 6 h apart) accompanied by proteinuria (≥ 300 mg in a 24-h urine collection or ≥ 2+ on a dipstick test). In cases where proteinuria is absent, PE may still be diagnosed if other clinical signs such as thrombocytopenia, impaired renal or liver function, pulmonary edema, or neurological disturbances are present. Eclampsia is defined as the onset of convulsions in a pregnant woman with PE that cannot be attributed to other identifiable neurological causes[4].

PE is characterized by a range of clinical symptoms, most notably persistent headache, visual disturbances, and right upper quadrant abdominal pain. Several risk factors increase the likelihood of developing PE, including chronic hypertension, pre-existing kidney disease, diabetes mellitus, a history of early-onset PE, maternal age > 40 years, first pregnancy, obesity, long intervals between pregnancies, oocyte donation, and autoimmune disorders[5,6].

PE poses significant risks to both the mother and fetus. Maternal complications include eclampsia, cerebral edema, stroke, and long-term cognitive or cardiovascular consequences, while fetal complications include intrauterine growth restriction, preterm birth, and stillbirth. Notably, termination of pregnancy remains the only definitive treatment for PE[7,8].

Current screening methods for PE primarily rely on maternal risk factors and uterine artery Doppler assessment, which, although useful, have limited predictive accuracy when used independently. This limitation has prompted growing interest in alternative vascular markers that better reflect early systemic hemodynamic changes. Recent studies have highlighted the potential role of ophthalmic artery Doppler (OAD) ultrasound for evaluating cerebral hemodynamics as a predictive tool for PE. The ophthalmic artery, a branch of the internal carotid artery, exhibits both anatomical and embryological similarities to cerebral vessels, making it a reliable surrogate for evaluating cerebral blood flow. This non-invasive technique is particularly valuable in low-resource settings where access to advanced diagnostic tools may be limited[9,10].

Previous studies have demonstrated altered OAD indices in women with established PE, indicating their role in disease characterization. However, evidence for its predictive value in early pregnancy remains unclear, as most studies have focused on late gestation, symptomatic cohorts, or cross-sectional designs. The limited prospective evidence in initially normotensive women during the second trimester, a crucial period for preventive intervention, highlights the need to assess whether OAD assessment in mid-pregnancy can predict the development of PE and enhance risk stratification[9-11]. Therefore, this study aimed to evaluate the predictive value of maternal OAD indices measured during the second trimester (17–23 weeks of gestation) for the subsequent development of PE in a cohort of initially normotensive pregnant women.

MATERIALS AND METHODS

Participant enrollment

This hospital-based prospective cohort study, including a diagnostic accuracy analysis, was conducted over a period of 1 year, from March 2024 to February 2025. Pregnant women attending the Antenatal Clinic during their second trimester were consecutively recruited and followed through the third trimester to monitor the development of PE. Written informed consent was obtained from all participants, and prior approval was obtained from the Institutional Ethics Committee. Consecutive recruitment was used to minimize selection bias.

Inclusion criteria

Eligible participants were pregnant women in their second trimester with no prior diagnosis of PE and no known high-risk factors for PE at the time of enrollment.

Exclusion criteria

Women were excluded if they declined to provide informed consent, had an uncertain last menstrual period that could not be confirmed by early ultrasonography, had known ocular pathologies, or had a history of chronic hypertension or renal disease.

Sample size

A total of 90 pregnant women who met the inclusion criteria were enrolled during the study period and followed until delivery; no participants were lost to follow-up.

Outcome definition

Index test: OAD parameters, including the resistive index (RI), pulsatility index (PI), first systolic peak velocity (P1), second systolic peak velocity (P2), and peak ratio (PR), measured in the second trimester.

Reference standard: PE was diagnosed according to the clinical guidelines of the American College of Obstetricians and Gynecologists and was defined as new-onset hypertension (blood pressure ≥ 140/90 mmHg on two separate readings at least 6 h apart) after 20 weeks of gestation with either proteinuria (≥ 300 mg in a 24-h urine collection or ≥ 2+ on a dipstick test) or evidence of maternal organ dysfunction. Blood pressure measurements and clinical assessments were performed during routine antenatal follow-up visits in the third trimester. The diagnosis was made by attending obstetricians as part of routine clinical care, and no formal blinding was applied between Doppler findings and outcome assessment, which may have introduced diagnostic review bias. This clinical diagnosis served as the reference standard for diagnostic accuracy analysis.

Doppler ultrasound technique

OAD was performed on the right eye using the Alpinion E-CUBE 8 ultrasound machine with a 3–12-MHz linear transducer. Doppler assessments were performed on the right ophthalmic artery to ensure procedural standardization and feasibility in a clinical setting. The participants were examined in the supine position after a 5-minute rest to minimize hemodynamic variability. The transducer was gently placed over the closed eyelid with coupling gel, and the ophthalmic artery was insonated approximately 15 mm from the optic disc. Pulsed-wave Doppler measurements were obtained with a 1–2-mm sample volume, insonation angle < 20°, a low wall filter (50–100 Hz), and a pulse repetition frequency of 2.5–4.0 kHz. Gain settings were optimized to obtain a clear waveform without background noise. All examinations were performed in real time by a single trained operator using a standardized Doppler ultrasonography protocol to ensure procedural consistency; however, intraobserver reproducibility was not formally assessed. Manual measurements of Doppler indices, including the second systolic peak velocity (P2), were obtained directly during image acquisition, and derived parameters such as PR were subsequently calculated using predefined formulas. The OAD waveform typically exhibits two systolic peaks. Four main indices were used for the analysis: P1, P2, PI, and PR, defined as the ratio of P2 to P1. While P1, RI, and PI were automatically generated by the ultrasound machine, P2 was measured manually, and the PR was calculated accordingly.

At least three consecutive uniform waveforms were recorded during maternal apnea to minimize respiratory variation. The following Doppler parameters were recorded: PI, RI, P1, P2, and PR (Figure 1). Cutoff values for Doppler parameters were derived using receiver operating characteristic (ROC) curve analysis with the Youden index within the same dataset; therefore, these thresholds should be considered exploratory and warrant external validation.

Figure 1  Ophthalmic artery Doppler image demonstrating the first systolic peak velocity (P1), second systolic peak velocity (P2), diastolic notch, and end-diastolic velocity (EDV).

For descriptive comparison, previously published reference OAD values (5^th–95^th percentile) were used: RI = 0.76 ± 0.08, PI = 1.87 ± 0.48, P1 = 36.66 ± 13.30 cm/s, P2 = 21.77 ± 9.89 cm/s, and PR = 0.59 ± 0.16. These reference ranges were not derived from the present study population and were used solely for descriptive interpretation and contextual comparison. They were not applied as diagnostic thresholds in the analysis[12].

Statistical analysis

Quantitative variables were expressed as mean ± SD for normally distributed data and as median with interquartile range for non-normally distributed data. Normality was assessed using the Shapiro–Wilk test. Categorical variables were presented as n (%). Comparisons between groups were performed using the independent-samples t-test for normally distributed continuous variables, the Mann–Whitney U test for non-normally distributed variables, and Fisher’s exact test for categorical variables. The diagnostic performance of OAD indices was evaluated using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy. ROC curve analysis was performed, and areas under the curve (AUC) with 95% confidence intervals (CIs) were calculated using the DeLong method. CIs for sensitivity, specificity, PPV, and NPV were calculated using the exact binomial method. A P-value < 0.05 was considered statistically significant.

Doppler parameters were initially analyzed as continuous variables and subsequently dichotomized for diagnostic performance assessment. Cutoff values for RI, PI, PR, P1, and P2 were derived from ROC curve analysis using the Youden index to optimize sensitivity and specificity for predicting PE. Accordingly, “low” and “high” categories were defined based on these data-driven thresholds to ensure reproducibility and consistency of classification. The observed values were compared with the established normal reference ranges for OAD velocimetry (5^th–95^th percentiles), as reported in the literature and described in the “Materials and methods” section.

RESULTS

A total of 90 participants were included in the analysis. The median gestational age at enrollment was 19.8 (interquartile range: 19.1–20.0) weeks, with a range of 17–23 weeks. The mean maternal age was 27.8 ± 4.6 (range, 20–37) years. The majority of participants (68.9%) were aged between 20 and 30 years (Table 1). Obstetric history showed that 42.2% of women were nulliparous and 86.7% had no prior abortions (Table 2).

Table 1 Age distribution of study participants.

Age group (yrs)	n (%)
20–30	62 (68.9)
31–40	28 (31.1)
mean ± SD	27.8 ± 4.6
Median (25th–75th percentile)	27.5 (24–32)
Range	20–37

Table 2 Obstetric characteristics of study participants.

Characteristic	n (%)
Gravida
1	35 (38.9)
2	33 (36.7)
3	20 (22.2)
4	2 (2.2)
Parity
0	38 (42.2)
1	32 (35.6)
2	19 (21.1)
3	1 (1.1)
Living children
0	38 (42.2)
1	34 (37.8)
2	17 (18.9)
3	1 (1.1)
Abortions
0	78 (86.7)
1	12 (13.3)
Gestational age at enrolment (weeks)
mean ± SD	19.6 ± 0.7
Median (25th–75th percentile)	19.9 (19.1–20)
Range	17–23

Distribution of OAD indices

The distribution of OAD parameters is summarized in Table 3. Low RI was observed in 51.1% of participants, with a mean RI of 0.71 ± 0.10. Low P1 values were found in 4.4% of participants, while low PI was observed in 32.2%. High P2 and high PR values were identified in 86.7% and 17.8% of participants, respectively (Figure 2).

Figure 2 Doppler imaging of the ophthalmic artery obtained from a patient who subsequently developed preeclampsia demonstrates an elevated second systolic peak velocity of 32 cm/second and a first systolic peak velocity of 52 cm/second, resulting in an increased peak ratio. EDV: End-diastolic velocity; P1: First systolic peak velocity; P2: Second systolic peak velocity.

Table 3 Distribution of ophthalmic artery Doppler indices according to receiver operating characteristic-derived cut-off values (n = 90).

Parameter	Category	n (%)	mean ± SD
RI	Low RI	46 (51.1)	0.71 ± 0.10
	Not low RI	44 (48.9)
P1	Low P1	4 (4.4)	61.9 ± 14.6 cm/s
	Not low P1	86 (95.6)
PI	Low PI	29 (32.2)	2.0 ± 0.3
	Not low PI	61 (67.8)
P2	High P2	78 (86.7)	33.9 ± 10.2 cm/s
	Not high P2	12 (13.3)
PR	High PR	16 (17.8)	0.5 ± 0.1
	Not high PR	74 (82.2)

Cutoff values for categorization were derived using receiver operating characteristic curve analysis and the Youden index. The following thresholds were used: RI < 0.60, PR > 0.60, PI < 1.80, P1 < 50 cm/second, and P2 > 30 cm/s.

P1: First systolic peak velocity; P2: Second systolic peak velocity; PI: Pulsatility index; PR: Peak ratio; RI: Resistive index.

Prevalence of PE

A total of 8 participants (8.9%) developed PE, whereas 82 (91.1%) remained normotensive (Table 4). Given the limited number of outcome events (n = 8), effect estimates and diagnostic performance metrics are presented with 95%CIs and should be interpreted with caution.

Table 4 Distribution of normotensive participants and those with preeclampsia.

Outcome	n (%)
Normotensive	82 (91.1)
Preeclampsia	8 (8.9)
Total	90 (100.0)

Association between Doppler indices and PE

Statistically significant associations were found between several Doppler parameters and PE. Women who subsequently developed PE demonstrated significantly lower second-trimester RI and PI values and higher PR values compared with women who remained normotensive (Table 5). Mean RI was significantly lower in the PE group (0.6 ± 0.1 vs 0.7 ± 0.1; mean difference: -0.2; P = 0.004). Similarly, mean PI was lower in those who developed PE (1.7 ± 0.2 vs 2.0 ± 0.3; mean difference: -0.4; P = 0.0003). In contrast, elevated PR was observed in 50% of participants with preeclampsia and in none of the normotensive women. The mean PR was significantly higher in the preeclamptic group (0.7 ± 0.1) than in the normotensive group (0.5 ± 0.1; mean difference: +0.2; P < 0.0001). Low P1 showed a significant difference in distribution (50% vs 6.9%; P = 0.038), but mean P1 values did not differ significantly between groups (56.8 ± 17.9 vs 62.4 ± 14.3; P = 0.307). High P2 did not show a significant association with PE in terms of distribution (10.3% vs 0%; P = 0.591) or mean values (39.7 ± 11.4 vs 33.3 ± 10.0; P = 0.085) (Table 5).

Table 5 Association between ophthalmic artery Doppler indices and the subsequent development of preeclampsia.

Parameter	Category	Normotensive, n (%)	Preeclampsia, n (%)	Total, n (%)	P value (distribution)	mean ± SD (preeclampsia)	mean ± SD (normotensive)	P value (mean)
RI	Not low RI	44 (100)	0 (0)	44 (100)	0.006	0.6 ± 0.1	0.7 ± 0.1	0.004
	Low RI	38 (82.61)	8 (17.39)	46 (100)
P1	Not low P1	80 (93.02)	6 (6.98)	86 (100)	0.038	56.8 ± 17.9	62.4 ± 14.3	0.307
	Low P1	2 (50)	2 (50)	4 (100)
PI	Not low PI	59 (96.72)	2 (3.28)	61 (100)	0.012	1.7 ± 0.2	2.0 ± 0.3	0.0003
	Low PI	23 (79.31)	6 (20.69)	29 (100)
P2	Not high P2	12 (100)	0 (0)	12 (100)	0.591	39.9 ± 11.4	33.3 ± 10.0	0.085
	High P2	70 (89.74)	8 (10.26)	78 (100)
PR	Not high PR	74 (100)	0 (0)	74 (100)	< 0.0001	0.70 ± 0.1	0.5 ± 0.1	< 0.0001
	High PR	8 (50)	8 (50)	16 (100)

P1: First systolic peak velocity; P2: Second systolic peak velocity; PI: Pulsatility index; PR: Peak ratio; RI: Resistive index.

Diagnostic performance of Doppler parameters

ROC curve analysis was performed to evaluate the discriminatory capacity of each Doppler parameter for predicting the subsequent development of PE. The diagnostic accuracy statistics for each Doppler parameter are presented in Table 6. PR demonstrated the highest AUC of 0.9 (95%CI: 0.8–0.9), suggesting excellent discrimination within this study dataset. Using the ROC-derived exploratory threshold, all eight women who developed PE had a positive PR result, yielding a sensitivity of 100% (95%CI: 63.1%–100%) and a specificity of 90.2% (95%CI: 81.9%–95.7%). Among the 82 women without PE, 74 were correctly classified as negative, resulting in an overall diagnostic accuracy of 91.1%. However, the PPV was 50% (8/16), reflecting the relatively low prevalence of PE (8.9%) in this cohort. The NPV was high, driven by both test performance and disease prevalence.

Table 6 Diagnostic performance of ophthalmic artery Doppler parameters for predicting preeclampsia.

Parameter	Low RI	Low P1	Low PI	High P2	High PR
Sensitivity (95%CI), %	100 (63.1–100)	25.0 (3.2–65.1)	75.0 (34.9–96.8)	100 (63.1–100)	100 (63.1–100)
Specificity (95%CI), %	53.7 (42.3–64.8)	97.6 (91.5–99.7)	71.9 (60.9–81.3)	14.6 (7.8–24.2)	90.2 (81.7–95.7)
AUC (95%CI)	0.77 (0.7–0.9)	0.6 (0.5–0.7)	0.7 (0.6–0.8)	0.6 (0.5–0.7)	0.9 (0.8–0.9)
Positive predictive value (95%CI), %	17.4 (7.8–31.4)	50.0 (6.8–93.2)	20.7 (7.9–39.7)	10.3 (4.5–19.2)	50.0 (24.6–75.4)
Negative predictive value (95%CI), %	100 (91.9–100)	93.0 (85.4–97.4)	96.7 (88.7–99.6)	100.0 (73.5–100.0)	100.0 (95.1–100.0)
Diagnostic accuracy, %	57.8	91.1	72.2	22.2	91.1%

AUC: Area under the curve; CI: Confidence interval; P1: First systolic peak velocity; P2: Second systolic peak velocity; PI: Pulsatility index; PR: Peak ratio; RI: Resistive index.

Low RI also identified all PE cases (8/8; sensitivity 100%, 95%CI: 63.1%–100%) but correctly identified only 44 of 82 women who did not develop PE, resulting in lower specificity (53.7%; 44/82) and modest overall accuracy (57.8%). Low PI showed a more balanced performance, correctly identifying 6 of 8 cases (75% sensitivity) and 59 of 82 non-cases (71.9% specificity), with an AUC of 0.7, indicating moderate discriminatory ability. Low P1 correctly identified 2 of 8 cases (25% sensitivity) but correctly classified 80 of 82 non-cases (97.6% specificity). High P2 identified all PE cases (8/8; 100% sensitivity) but misclassified most non-cases, with only 12 of 82 correctly identified as negative (14.6% specificity).

Overall, PR showed the highest diagnostic performance, with an AUC of 0.9, outperforming both RI (AUC = 0.7) and PI (AUC = 0.7) (Table 6, Figure 3). The lower AUC values for RI and PI further support the relative superiority of PR within this cohort. However, the 100% sensitivity observed for PR was based on a limited number of outcome events (n = 8), resulting in wide confidence intervals and statistical instability, highlighting the need for cautious interpretation of these findings.

Figure 3  Diagnostic performance of ophthalmic artery Doppler parameters for predicting preeclampsia. The figure compares the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of low resistive index, low first systolic peak velocity, low pulsatility index, high second systolic peak velocity, and elevated peak ratio.

DISCUSSION

This prospective observational study aimed to evaluate the predictive value of maternal OAD parameters, namely RI, PI, P1, P2, and PR, for the subsequent development of PE. These Doppler parameters were measured during the second trimester in initially normotensive women, and statistically significant differences were observed in RI, PI, and, particularly, PR between women who subsequently developed PE and those who remained normotensive. Notably, PR emerged as the most reliable predictor among the evaluated parameters (P < 0.001).

The physiological basis underlying the diagnostic utility of PR lies in the altered ophthalmic artery waveform morphology. In normotensive pregnancies, the two systolic peaks are distinct and reflect normal vascular compliance. In contrast, PE is associated with altered waveform morphology and cerebrovascular dysregulation, resulting in an increased PR. Although previous studies have associated elevated PR with increased P2, our findings suggest that PR elevation may not necessarily be driven by an absolute increase in P2 alone. Given the limited diagnostic performance of P2 as an independent parameter, the observed increase in PR may instead reflect a relative reduction in P1 amplitude, leading to a proportionally higher P2/P1 ratio. This altered waveform pattern is likely related to impaired vascular compliance, endothelial dysfunction, and disturbed downstream vascular impedance. Furthermore, the loss of cerebral autoregulation in PE may contribute to cerebral hyperperfusion and increased transmission of pulsatile energy to the ophthalmic circulation, thereby altering waveform morphology before the onset of clinical neurological manifestations[13-15].

Compared with uterine and fetal Doppler studies, which reflect placental and fetal perfusion, respectively, OAD offers a unique perspective on maternal cerebral circulation. While uterine Doppler identifies placental insufficiency, it may not fully capture maternal endothelial dysfunction or risk of neurological complications. Therefore, OAD offers clinical complementary value by reflecting the cerebral autoregulatory impairment associated with severe PE and eclampsia. This distinction is clinically relevant, particularly in severe or early-onset PE, where neurological manifestations are more common[16-19].

Our findings are consistent with those reported by de Melo et al[13], who demonstrated the high diagnostic performance of PR. Similarly, Sarno et al[14] identified a strong temporal association between abnormal PR and the onset of PE. Our findings further support the concept that PR reflects broader alterations in ophthalmic artery waveform morphology and cerebrovascular hemodynamics rather than an isolated elevation of P2 alone.

The lower RI and PI values observed in women who developed PE align with the findings of Olatunji et al[10] and Muthyal et al[15], suggesting a state of cerebral hyperperfusion and reduced vascular impedance in PE. Furthermore, Kalafat et al[16] and Alves et al[17] emphasized the potential of OAD as a simple and dependable tool for the early detection of PE. While the integration of OAD with biochemical markers, as explored by Sapantzoglou et al[18], could further enhance its predictive accuracy, our study confirms that PR alone remains a strong independent predictor of PE.

A key strength of our study is its prospective design and the assessment of Doppler parameters during the second trimester in initially asymptomatic women, allowing us to assess true predictive rather than diagnostic correlations. Clinically, the high sensitivity and NPV of PR suggest potential utility for identifying women at low risk of PE and improving early risk stratification. Additionally, the simplicity and noninvasive nature of OAD allowed for consistent data collection with minimal operator bias. Therefore, integrating OAD into routine maternal evaluation alongside conventional fetal and placental assessments can improve patient monitoring and bridge gaps in comprehensive prenatal care.

This study has several limitations that should be considered when interpreting the findings. First, the small number of PE cases (n = 8) substantially limited statistical power and may have resulted in imprecise and potentially overestimated diagnostic performance estimates. Additionally, the ROC-derived cutoff values were internally generated and should be considered exploratory, requiring external validation in larger independent cohorts. Second, the single-center design may restrict the generalizability of the findings to broader populations. Third, Doppler measurements were obtained at a single time point; therefore, serial assessments may provide superior predictive value and better reflect dynamic hemodynamic changes that occur during pregnancy. Fourth, the absence of multivariable analysis precludes evaluation of the independent predictive contribution of OAD parameters beyond established risk factors such as maternal age, body mass index, parity, and family history of PE. Furthermore, baseline clinical variables were not retained in an outcome-stratified individual-level format, preventing subgroup comparisons and limiting assessment of potential confounding by baseline risk factors.

In addition, all examinations were performed by a single trained operator to ensure procedural consistency; however, formal assessment of intraobserver reproducibility, including repeated measurements or blinded review of stored images, was not performed. In addition, outcome assessment was not blinded to Doppler findings, as these results were available during routine antenatal evaluation, introducing the possibility of diagnostic review bias that may have influenced clinical diagnosis or management decisions.

Finally, the study lacked external validation and did not include comparisons with established PE screening modalities, including uterine artery Doppler, serum biomarkers (e.g., placental growth factor and soluble fms-like tyrosine kinase-1), or the Fetal Medicine Foundation competing-risk model, thereby limiting assessment of the incremental and comparative predictive value of OAD within current screening frameworks.

Future studies incorporating multivariate logistic regression analyses are warranted to evaluate whether OAD parameters provide incremental predictive value beyond established clinical risk factors, including body mass index, baseline blood pressure, and obstetric history. Although OAD demonstrated promising diagnostic performance with potential utility in resource-limited settings, its accuracy remains operator-dependent. Therefore, standardized training and protocol harmonization are essential to ensure reproducibility and consistently achieve the reported diagnostic accuracy across clinical settings.

CONCLUSION

Maternal OAD indices were significantly associated with the development of PE, with reduced RI and PI values and elevated PR values, suggesting possible early vascular and cerebral hemodynamic changes. Among the evaluated parameters, PR (P2/P1) demonstrated the highest exploratory predictive performance in this cohort. These findings support further investigation of OAD Doppler parameters as adjunctive risk-stratification markers in larger prospective studies with external validation before their potential role in routine antenatal assessment can be determined.