The efficacy of different ultrasound Doppler parameters in predicting adverse fetal outcomes in pregnancies with hypertensive disorders: a systematic review and meta-analysis

Introduction

Hypertensive disorders of pregnancy (HDP), including gestational hypertension, preeclampsia, eclampsia, and chronic hypertension with superimposed preeclampsia, remain a leading cause of maternal and perinatal morbidity and mortality worldwide (1). Gestational hypertension is defined as a systolic blood pressure of 140 mmHg or more or a diastolic blood pressure of 90 mmHg or more, or both, on two occasions at least 4 hours apart after 20 weeks of gestation, in a woman with a previously normal blood pressure (2). Preeclampsia is new-onset hypertension most often occurring after the 20th week of gestation, accompanied by either proteinuria or any of the following signs or symptoms: thrombocytopenia, impaired liver function, kidney insufficiency, pulmonary edema, new-onset headache unresponsive to medication, or visual disturbances. Eclampsia, a convulsive symptom of hypertensive disorders during pregnancy, represents one of the graver manifestations of this condition (3). Eclampsia is a new onset of seizures in the absence of other potential causes such as epilepsy (4). Chronic (or preexisting) hypertension is present prior to pregnancy and is typically diagnosed before pregnancy or within the first 20 weeks of gestation (5). Epidemiological data have indicated a concerning rising trend in HDP prevalence in the United States, escalating from 500 cases per 10,000 deliveries in 1993 to 1021 cases per 10,000 deliveries in 2016–2017 (1). Beyond maternal risk, HDP is significantly associated with adverse fetal-neonatal outcomes, including preterm birth, intrauterine growth restriction (IUGR), placental abruption, and perinatal mortality (6).

As a noninvasive and safe examination technique, Doppler ultrasound has been extensively applied in the diagnosis of obstetric-related diseases. It is currently believed that the development of HDP primarily involves two stages (7,8): inadequate placental formation and the subsequent placental oxidative stress. During early pregnancy, abnormal placental development leads to insufficient remodeling of the spiral arteries, resulting in reduced placental perfusion, local ischemia, and hypoxia. This process triggers the release of various growth factors from the placenta into the maternal circulation, activating a systemic inflammatory response, impairing maternal endothelial function, and ultimately leading to multi-organ dysfunction and the corresponding clinical manifestations. Therefore, by assessing the blood flow waveforms of the fetal umbilical artery (Figure 1), fetal middle cerebral artery (MCA) (Figure 2), fetal ophthalmic artery, and maternal uterine artery (Figure 3), the relationship between Doppler parameters and adverse fetal outcomes in HDP can be evaluated. Studies have confirmed that parameters such as umbilical artery pulsatility index (UA PI), cerebroplacental ratio [CPR; calculated as the middle cerebral artery PI (MCA-PI) divided by the UAPI], and uterine artery Doppler index (UtA) have utility in prognosticating adverse outcomes (9,10). However, there is currently no clear conclusion regarding which of these parameters demonstrates a stronger correlation.

Figure 1 Transabdominal Doppler ultrasound image of the fetal UA in a 38-year-old woman with hypertensive disorders of pregnancy (gestational age: 28⁺¹ weeks). The result of the ultrasound Doppler of the umbilical artery of this mother was absent end-diastolic flow velocity. The follow-up of the fetal outcome was neonatal death. EDV, end-diastolic velocity; HR, hazard ratio; PI, pulsatility index; PSV, peak systolic velocity; RI, resistance index; S/D, peak systolic velocity/end-diastolic velocity; UA, umbilical artery.

Figure 2 Transabdominal Doppler ultrasound image of the fetal middle cerebral artery in a 26-year-old normotensive mother (gestational age: 36⁺² weeks). This mother had a high fetal middle cerebral artery pulsatility index value (greater than the 95th percentile) on fetal middle cerebral artery Doppler ultrasonography, and the fetal outcome was preterm. DG, depth gain; F, frequency; HR, hazard ratio; PI, pulsatility index; RI, resistance index; S/D, peak systolic velocity/end-diastolic velocity.

Figure 3 Transabdominal Doppler ultrasound image of the maternal uterine artery in a 30-year-old woman with hypertensive disorders of pregnancy (gestational age: 26⁺² weeks). This mother had a high uterine-artery pulsatility index value (greater than the 95th percentile) on uterine-artery Doppler ultrasonography, and the fetal outcome was preterm. EDV, end-diastolic velocity; HR, hazard ratio; PI, pulsatility index; PSV, peak systolic velocity; RI, resistance index; S/D, peak systolic velocity/end-diastolic velocity.

Thus, this study aimed to employ a network meta-analysis to compare different ultrasound Doppler parameters in their association with adverse fetal outcomes. We present this article in accordance with the PRISMA reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-954/rc).

Methods

Data sources, search strategy, and selection criteria

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases from database inception to November 13, 2024. Any cohort studies investigating that Doppler ultrasonography for predicting the fetal pregnancy outcomes of pregnant women with HDP were eligible for inclusion in this study. There was no language restriction. The search strategy included the following terms with medical subject headings and free words: “hypertension, pregnancy-induced”, “pre-eclampsia”, “eclampsia”, “chronic hypertension with superimposed pre-eclampsia”, “ultrasonography, Doppler”, and “cohort studies”. The reference lists of retrieved studies were also manually searched to identify other eligible studies. Two authors independently (X.H. and K.Z.) completed the reference search and study selection, and any disagreements were solved through discussion until an agreement was reached. The inclusion criteria were as follows: (I) a cohort study design, (II) a diagnosis of HDP with a singleton pregnancy, (III) a Doppler ultrasound parameter investigated as an indicator, (IV) any fetal and neonatal outcomes, and (V) a Newcastle-Ottawa Scale (NOS) score ≥6. Meanwhile, the exclusion criteria were as follows: (I) nonoriginal research, (II) animal experiments and other basic research literature, and (III) incomplete reporting of data.

Data collection and quality assessment

We abstracted data information and assessed the quality of included studies. The collected information from the retrieved studies included the first author’s name, publication year, research type, sample size, age, Doppler indicators (e.g., UA, CPR, and UtA), and outcome [e.g., preterm birth, low birth weight (LBW), and neonatal intensive care unit (NICU) admission]. Study quality was assessed via the NOS. Two researchers (H.X. and Z.K.) independently evaluated the risk of bias of the included studies based on the selection of the study population, comparison between groups, and pregnancy outcomes using the NOS. A third researcher (F.Y.) was consulted when there was disagreement.

Doppler ultrasound parameters

For umbilical artery, measurements should be made in a free cord loop. The waveform with the largest systolic peak was chosen as the result. The selected waveform was used to measure the parameters of the PI and half peak systolic velocity deceleration time (hPSV-DT). The calculation method for the UA PI is as follows: UA PI=UA PSV−UA EDVUA TAmax, where PSV is the peak systolic blood flow velocity, EDV is the peak diastolic blood flow velocity, and TAmax is the time-averaged maximum velocity. The hPSV-DT assays were conducted as described by Bustos et al. (11): on the selected waveform, the first caliper was placed at the peak of the contraction velocity, while the second caliper was positioned at the midpoint of the maximum velocity. A line was then drawn from the second caliper to the spectral waveform, and the deceleration time within this interval—specifically, the peak systolic velocity—was measured in milliseconds. Subsequently, a straight line was drawn from the second caliper to intersect with the spectral waveform, and the deceleration time during this interval was recorded in milliseconds. For the MCA, color flow mapping was used to identify the circle of Willis, and the proximal portion of the MCA was located caudal to the transthalamic plane. The formula for calculating the MCA PI is as follows: MCA PI=MCA PSV−MCA EDVMCA TAmax. The major branches of the uterine artery can be clearly identified at the cervicofundal junction with real-time color Doppler ultrasound. Doppler velocity measurements are typically obtained near this anatomical region, through either a transabdominal or transvaginal approach. The chosen waveform was used to measure the parameters of PI and resistance index (RI). The UtA PI and RI were calculated the following respective formula: UtA PI=UtA PSV−UtA EDVUtA TAmax; RI=UtA PSV−UtA EDVUtA PSV.

Outcomes

The adverse neonatal outcomes included preterm birth, LBW, NICU admission, fetal growth restriction (FGR), respiratory distress syndrome (RDS), Apgar score <7 at 5 minutes, neonatal death, intracranial hemorrhage, small for gestational age (SGA), and acidemia. Preterm birth was defined as a delivery occurring prior to 37 completed weeks of gestation. LBW was defined as a live-born infant weighing below 2,500 grams. FGR was defined as a pathological condition in which the fetus fails to achieve its expected growth potential, corresponding to SGA fetuses with an ultrasonographically estimated fetal weight or abdominal circumference below the 10th percentile for gestational age. RDS is primarily caused by pulmonary surfactant deficiency in the context of lung immaturity and manifests as acute respiratory distress shortly after birth. Biochemical acidemia was defined as a fetal scalp blood pH <7.25.

Statistical analysis

Based on the frequentist framework for network meta-analysis, Stata 17.0 software (StataCorp. College Station, TX, USA) was used for graphing and data analysis. Odds ratios (ORs) were used as effect measures for dichotomous variables and are presented with their 95% confidence intervals (CIs). Global inconsistency was assessed through visualization via a network heatmap, while local inconsistency was examined with the node-splitting method in the comparison of direct and indirect evidence. League tables were used to present the comparative results of outcome indicators for any two Doppler parameters. A random-effects model was employed to calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Heterogeneity was assessed via the Q-test and I² statistic. A significance level of P<0.05 or an I²>50% indicated substantial heterogeneity among the included studies, necessitating further determination of heterogeneity sources through subgroup analysis or meta-regression.

Results

Literature search and risk-of-bias assessment

The details of the literature research and eligible studies are presented in Figure 4. A total of 779 articles were selected from the CENTRAL, PubMed, Embase, CNKI, and Wanfang Data. Among the initially included studies, 617 were excluded due to duplication, 41 due to their article types, and 8 due to lacking a full text. Consequently, during the first selection round, 682 articles were excluded according to the title and abstracts. A total of 50 full texts were screened again, among which 3 were excluded due to a lack of comparisons, 23 due to no reported outcomes, and 15 due to the patients being unqualified. We also retrieved the reference lists of the included studies. Ultimately, 21 studies were selected for meta-analysis. The details of included studies are summarized in Table 1.

Figure 4 PRISMA flowchart summarizing the inclusion of studies in the systematic review and meta-analysis.

Network meta-analysis

The network diagram of ultrasound Doppler parameters in predicting adverse fetal outcomes, such as preterm birth, LBW, and FGR, is provided in Figure S1. No closed loops were formed among the ultrasound Doppler parameters. The consistency model test (P>0.05) indicated good consistency.

Twenty-one studies investigated the relationship between eight ultrasound Doppler parameters and preterm birth. As shown in Figure 5, abnormal UA PI (OR =21.60; 95% CI: 6.32–73.84), abnormal umbilical artery half peak systolic velocity deceleration time (UA hPSV-DT), UA absent/reversed end-diastolic flow velocity in the umbilical artery (AREDF), abnormal UtA P I (OR =13.71, 95% CI: 4.53–41.46), abnormal uterine artery resistance index (UtA RI), the presence of a UA diastolic notch, and abnormal CPR were all significantly associated with an increased risk of preterm birth. However, abnormal OA PR was associated with an increased risk, but the difference was not statistically significant.

Figure 5 Network meta-analysis results for preterm birth. Data are presented as odds ratio (95% CI). CI, confidence interval; CPR, cerebroplacental ratio [middle cerebral artery pulsatility index (MCA-PI)/umbilical artery PI (UA-PI)]; OA PR, fetal ophthalmic artery peak ratio [the ratio of the flow velocity of the second peak (P2) to that of the initial systolic velocity peak (P1)]; UA AREDF, umbilical artery absent/reversed end-diastolic flow velocity in the umbilical artery; UA hPSV-DT, umbilical artery half peak systolic velocity deceleration time; UA PI, umbilical artery pulsatility index; UtA, uterine artery Doppler index; UtA PI, uterine artery pulsatility index; UtA RI, uterine artery resistance index.

Twenty-one studies explored the relationship between four ultrasound Doppler parameters and LBW. According to Figure 6, abnormal UA PI, abnormal UA AREDF, abnormal UA hPSV-DT, and abnormal CPR (OR =4.90, 95% CI: 2.62–9.19) were all significantly associated with an increased risk of LBW. Furthermore, compared to abnormal CPR, abnormal UA PI was associated with a significantly higher risk of LBW (OR =5.83, 95% CI: 1.51–22.50).

Figure 6 Network meta-analysis results for low birth weight. Data are presented as odds ratio (95% CI). CI, confidence interval; CPR, cerebroplacental ratio [middle cerebral artery pulsatility index (MCA-PI)/umbilical artery PI (UA-PI)]; UA AREDF, umbilical artery absent/reversed end-diastolic flow velocity in the umbilical artery; UA hPSV-DT, umbilical artery half peak systolic velocity deceleration time; UA PI, umbilical artery pulsatility index.

Twenty-one studies examined the relationship between seven ultrasound Doppler parameters and NICU admission. As shown in Figure 7, abnormal UA PI, abnormal UA hPSV-DT, abnormal CPR, and abnormal UtA RI (OR =3.64, 95% CI: 1.18–11.24) were significantly associated with an increased risk of NICU admission. However, UtA PI, the presence of a UA diastolic notch, and abnormal ophthalmic artery peak ratio (OA PR) were not significantly associated with NICU admission.

Figure 7 Network meta-analysis results for NICU admission. Data are presented as odds ratio (95% CI). CI, confidence interval; CPR, cerebroplacental ratio [middle cerebral artery pulsatility index (MCA-PI)/umbilical artery PI (UA-PI)]; OA PR, fetal ophthalmic artery peak ratio [the ratio of the flow velocity of the second peak (P2) to that of the initial systolic velocity peak (P1)]; UA hPSV-DT, umbilical artery half peak systolic velocity deceleration time; UA PI, umbilical artery pulsatility index; UtA, uterine artery Doppler index; UtA PI, uterine artery pulsatility index; UtA RI, uterine artery resistance index.

Twenty-one studies investigated the relationship between five ultrasound Doppler parameters and FGR. According to Figure 8, UA AREDF, abnormal UtA RI or presence of a UA diastolic notch, abnormal UtA PI, and abnormal CPR were significantly associated with an increased risk of FGR. Additionally, compared to UA AREDF, abnormal UtA RI or presence of a diastolic notch (OR =3.22; 95% CI: 1.27–8.19) and abnormal UtA PI (OR =3.08; 95% CI: 1.19–7.97) were associated with a significantly higher risk of FGR.

Figure 8 Doppler indicators predict fetal growth restriction. Data are presented as odds ratio (95% CI). CI, confidence interval; CPR, cerebroplacental ratio [middle cerebral artery pulsatility index (MCA-PI)/umbilical artery PI (UA-PI)]; UA AREDF, umbilical artery absent/reversed end-diastolic flow velocity in the umbilical artery; UtA PI, uterine artery pulsatility index; UtA RI, uterine artery resistance index.

The associations between other ultrasound Doppler indicators and other adverse fetal outcomes (RDS, 5-minute Apgar score <7, neonatal death, intracranial hemorrhage, SGA, and fetal acidemia) are shown in Figures S2-S7.

Diagnostic value

The sensitivity and specificity of different ultrasound Doppler parameters for predicting adverse fetal outcomes such as preterm birth, LBW, and FGR are shown in Figures S8-S15. These results indicated that UA Doppler parameters and the CPR have a degree of value in predicting these adverse fetal outcomes.

Discussion

HDP is among the primary causes of global maternal and perinatal mortality (33). Doppler ultrasound parameters, valued for their noninvasive nature and operational simplicity, hold significant predictive value in the prognostic assessment of obstetric conditions. Although the precise mechanisms linking abnormal fetal and maternal Doppler parameters to adverse fetal outcomes in HDP have not yet fully elucidated, evidence suggests that inadequate uteroplacental perfusion, resulting from impaired spiral artery remodeling or placental vascular dysfunction, may represent a key underlying pathway (34,35). Recent studies have consistently supported the considerable prognostic utility of Doppler ultrasound in the clinical management of HDP. For instance, elevated UtA PI has been observed in HDP patients as early as the first trimester in comparison to normotensive controls, indicating its potential for early risk stratification. Furthermore, UA hemodynamic parameters and CPR exhibit high sensitivity in identifying fetuses at high risk of adverse perinatal outcomes. These findings collectively suggest that Doppler ultrasound parameters represent promising tools for assessing fetal prognosis in HDP, warranting further in-depth investigation.

This study systematically reviewed 21 studies examining the application of Doppler ultrasound for predicting fetal outcomes in pregnancies complicated by HDP. The analysis indicated that UA parameters, UtA parameters, and CPR are significant risk factors for adverse fetal outcomes.

The meta-analysis revealed that abnormal UA PI and UA AREDF are significantly associated with multiple adverse outcomes, such as preterm birth and LBW. The UA is an important part of the fetal circulatory system, which is responsible for the material exchange between the fetus and the placenta. The UA blood flow velocity waveform can indirectly reflect placental function and whether the fetus is at risk of hypoxia or acidosis. In Trudinger et al.’s (36) study, it was shown that abnormal UA RI strongly correlated with adverse fetal outcomes, and in Rochelson et al.’s study (37), UA ARED was significantly associated with adverse fetal outcomes, which aligns with our results.

Additionally, abnormal CPR was identified as a risk factor for several adverse outcomes, including a 5-minute Apgar score <7, NICU admission, and FGR. The CPR is an indicator of the balance between fetal brain and placental blood flow on Doppler ultrasound. In DeVore et al.’s study (9), it was reported that the CPR is an important predictor of adverse pregnancy outcomes. Additionally, its predictive breadth was supported by Khalil et al.’s findings, specifically that abnormal CPR independently predicts NICU admission, underscoring its role in holistic fetal risk stratification (38).

The network meta-analysis conducted in this study revealed abnormal UA PI demonstrated significantly superior efficacy in predicting LBW than did abnormal CPR. For FGR, both abnormal UtA RI/present UtA diastolic notch and abnormal UtA PI showed significantly superior efficacy compared to UA AREDF.

Conversely, whether abnormal OA PR and cerebro-umbilical (CU) ratio are risk factors for most adverse fetal outcomes remains to be clarified in further evaluation. Chaves et al. (19) reported only a weak correlation between OA PR and fetal prognosis in women with severe HDP, while Simanaviciute and Gudmundsson (39) found no significant association between an abnormal CU ratio and a low Apgar score (<7). These results collectively suggest that the clinical application of abnormal OA PR and CU parameters in prenatal risk stratification has certain limitations.

Clinical implications

This study established that abnormal Doppler parameters of the abnormal UA, CPR, and UtA are significant risk factors for adverse fetal outcomes in pregnancies complicated by hypertensive disorders. These hemodynamic markers demonstrated clinical utility in anticipating preterm delivery, LBW, intrapartum fetal distress, and neonatal mortality. Based on our findings, we recommend that obstetric providers managing high-risk pregnancies with established or suspected hypertensive disorders do the following: First, implement serial Doppler surveillance of UA, CPR, and UtA waveforms. Second, incorporate trajectory analysis of these biometric parameters into risk stratification protocols. Third, initiate timely interventions when deteriorating hemodynamics are predictive of a compromised fetal status. Such proactive monitoring may mitigate perinatal morbidity and optimize neonatal survival outcomes. Moreover, we discovered that HDP is associated with fetal growth parameters such as femur length (40). Therefore, in future studies, we can add fetal growth parameters to analyze their association with adverse fetal outcomes.

Limitations

Certain limitations to this study should be addressed. First, we directly employed indirect comparisons from the network meta-analysis without a common control group, which carried a certain risk of bias. Second, there was high heterogeneity due to the excessively wide CIs. Third, the study population was for singleton pregnancies only.

Conclusions

In the population with HDP, abnormal UA PI and CPR are risk factors for multiple adverse fetal outcomes. Moreover, abnormal UA PI is associated with a higher risk of LBW than is abnormal CPR; additionally, compared to UA AREDF, abnormal UtA RI/the presence of a UA diastolic notch and abnormal UtA PI are associated with higher risk of FGR.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-954/rc

Funding: This study was supported by the AI-Based Prenatal Ultrasound Assisted Diagnostic and Quality Control System (Project ID: 2024-YF05-00418-SN).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-954/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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