Impact of an Umbilical Artery S/D Ratio ≤ 5th Percentile on Pregnancy Outcomes: A Retrospective Cohort Study

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Methods This was a single-center retrospective cohort study that included 1,790 singleton pregnant women who underwent umbilical artery Doppler examinations at Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University between January 2023 and December 2025. Inclusion criteria were: gestational age ≥ 36 weeks and complete S/D ratio records. Exclusion criteria included persistently elevated S/D ratios, absent or reversed end-diastolic flow; multiple pregnancies; and fetal structural or chromosomal abnormalities. Low S/D ratio was defined as an initial measurement ≤5th percentile. Persistent low S/D was defined as all measurements ≤5th percentile, while non-persistent low S/D was defined as only some measurements meeting this criterion. After random 1:1 matching by gestational age, 444 cases were included in each group. Multivariable logistic regression analysis was performed to examine the role of umbilical cord abnormalities, fetal distress, neonatal birth weight, and maternal comorbidities. Primary outcomes included Apgar score < 7 at 5 minutes, admission to neonatal intensive care unit (NICU), and neonatal respiratory distress. Secondary outcomes comprised mode of delivery, fetal distress rate, and the interval from first detection of low S/D to delivery. Outcomes were compared after stratifying by the gestational age at first detection of low S/D into two-week intervals (36–37, 38–39, and 40–41 weeks). Results Among the 1,790 included cases, 1,056 had documented low S/D ratios (based on 2,125 total measurements), comprising 612 cases in the persistent group and 444 in the non-persistent group. After matching, 444 cases were included in each group. No stillbirths occurred in either group. Compared with the non-persistent group, the persistent group had a shorter interval from detection to delivery (20.4 ± 8.7 days vs. 26.8 ± 6.5 days, P < 0.001) and lower neonatal birth weight (3312 ± 518 g vs. 3428 ± 462 g, P = 0.012). There were no statistically significant differences between groups in the rates of Apgar score < 7 at 5 minutes, NICU admission, or neonatal respiratory distress. The rate of umbilical cord abnormalities was higher in the persistent group (15.3% vs. 10.1%, P = 0.05). Stratified analysis revealed that among the 40–41 weeks group, the persistent low S/D subgroup had a higher rate of fetal distress (6.1% vs. 2.4%). Gestational age at first detection of low S/D was negatively correlated with the interval to delivery (r=-0.32, P < 0.001). Multivariable logistic regression analysis demonstrated that the pattern of low S/D (persistent vs. non-persistent) was not an independent predictor (OR = 1.08, 95% CI: 0.75–1.56, P = 0.68); however, umbilical cord abnormalities (OR = 3.12, 95% CI: 1.89–5.15, P < 0.001) and fetal distress (OR = 4.32, 95% CI: 2.18–8.56, P < 0.001) were identified as independent risk factors. Conclusions This large-sample retrospective cohort study demonstrates that persistent low S/D ratio, compared with non-persistent low S/D, is associated with a higher rate of umbilical cord abnormalities. Gestational age-stratified analysis suggests that persistent low S/D at advanced gestational ages may increase the risk of fetal distress. Gestational age at first detection of low S/D was negatively correlated with the interval to delivery. Multivariable analysis indicates that low S/D ratio accompanied by umbilical cord abnormalities and fetal distress are independent predictors of adverse pregnancy outcomes. Trial registration: not applicable. Umbilical artery S/D ratio Low blood flow resistance Perinatal outcomes Fetal distress Umbilical cord abnormalities Gestational age stratification Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Umbilical artery Doppler assessment during pregnancy is a core technique for monitoring fetal well-being, with the systolic/diastolic (S/D) ratio serving as the most commonly used parameter and having been incorporated into international guidelines for high-risk pregnancy management [ 1 ]. Elevated S/D ratios reflect increased placental vascular resistance and are frequently associated with fetal growth restriction, hypoxia, and adverse perinatal outcomes [ 2 ]. However, the clinical significance of a low S/D ratio (≤ 5th percentile) has long been overlooked. Existing research has predominantly focused on elevated values, with few systematic investigations into the potential pathological implications of low values [ 16 ]. A low S/D ratio may result from placental hyperperfusion, umbilical cord structural abnormalities (such as torsion, true knot, or thrombosis), or decreased vascular resistance due to increased fetal cardiac output [ 6 , 13 ]. A case series reported eight cases of persistently low S/D ratios, all of which were accompanied by severe umbilical cord pathologies including thrombosis, excessive torsion, and true knot, suggesting that persistent low S/D may serve as an early warning signal for acute umbilical cord events [ 4 ]. Other studies have shown that low umbilical artery resistance is associated with normal pregnancy outcomes; however, these investigations were limited by small sample sizes and failed to distinguish between persistent and non-persistent patterns [ 10 ]. Comparative studies examining persistent versus non-persistent low S/D ratios, as well as the influence of gestational age, are even scarcer. In clinical practice, the absence of unified management guidelines for low S/D ratios often leads clinicians to regard it as a "physiological variant," potentially delaying timely intervention [ 1 ]. The present study employs a large-sample, single-center retrospective cohort design to systematically compare the impact of persistent versus non-persistent low S/D ratios on perinatal outcomes, with detailed gestational age-stratified analysis. By employing multivariable regression and survival analysis, we aimed to identify independent risk factors and provide evidence-based guidance for clinical decision-making regarding low S/D ratios. Methods Study Design and Ethics This was a single-center retrospective cohort study that included 1,790 women with singleton pregnancies who underwent umbilical artery Doppler examinations at Shandong Provincial Maternal and Child Health Care Hospital between January 2023 and December 2025. The study was approved by the Ethics Committee of Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University (approval number: SFYWZLP2026-005), and the protocol adhered to the STROBE reporting guidelines for observational studies [ 21 ]. Inclusion and Exclusion Criteria Inclusion criteria were: gestational age ≥ 36 weeks, singleton pregnancy, and at least one complete umbilical artery S/D ratio record. Exclusion criteria included persistently elevated S/D ratios, absent or reversed end-diastolic flow; multiple pregnancies; and fetal structural or chromosomal abnormalities. Definition and Grouping of S/D Ratio Low S/D ratio was defined as an initial measurement ≤5th percentile based on the gestational age-specific reference ranges established by Acharya et al [ 3 ]. Persistent low S/D was defined as all measurements ≤5th percentile, while non-persistent low S/D was defined as at least one, but not all, measurements ≤5th percentile. A computer-generated 1:1 random algorithm was used to match the persistent and non-persistent groups according to gestational age at first detection of low S/D, resulting in 444 cases in each group to ensure baseline comparability. Data Collection The following variables were extracted from the electronic medical record system: maternal age, parity, comorbidities (including gestational diabetes mellitus, scarred uterus, hypertensive disorders), mode of conception, type of fetal heart rate monitoring, gestational age at first detection of low S/D, percentile value, S/D ratio, days of expectant management, gestational age at delivery, mode of delivery, umbilical cord abnormalities (such as torsion, thrombosis), neonatal birth weight, and Apgar scores. All data were independently extracted and cross-checked by two researchers. Outcome Measures Primary outcomes included: Apgar score < 7 at 5 minutes, admission to the neonatal intensive care unit (NICU), and neonatal respiratory distress (defined by clinical diagnosis or Apgar score < 7 at 5 minutes). Secondary outcomes comprised: cesarean section rate, fetal distress (explicitly documented as indication for delivery or intraoperative finding), and the interval from first detection of low S/D to delivery (in days). Outcomes were compared after stratifying by gestational age at first detection of low S/D into two-week intervals: 36–37 weeks, 38–39 weeks, and 40–41 weeks. Statistical Analysis Statistical analyses were performed using SPSS version 26.0. Continuous variables were presented as mean ± standard deviation and compared between groups using the independent samples t-test. Categorical variables were expressed as frequencies and percentages and compared using the chi-square test or Fisher's exact test, as appropriate. The interval from first detection of low S/D to delivery was analyzed using the Kaplan-Meier method, with survival curves generated and compared between groups using the log-rank test. Multivariable logistic regression analysis was performed to identify independent predictors of adverse outcomes (defined as Apgar score < 7 at 5 minutes or neonatal respiratory distress), with covariates including group allocation (persistent vs. non-persistent low S/D), gestational age at first detection of low S/D, umbilical cord abnormalities, fetal distress, maternal age, and maternal comorbidities. Pearson correlation analysis was used to assess the relationship between gestational age at first detection of low S/D and the interval to delivery. A two-tailed P-value < 0.05 was considered statistically significant. Results General Characteristics Among the 1,790 pregnant women included in the study, 1,056 had documented low S/D ratios, yielding a total of 2,125 individual measurements. Of these, 612 cases were classified as persistent low S/D and 444 as non-persistent low S/D (Fig. 1). After matching, baseline characteristics were well-balanced between the two groups (Table 1). The mean maternal age was 31.0 years, and the mean gestational age at first detection of low S/D was 37.9 weeks. The most common maternal comorbidities were gestational diabetes mellitus (22.1%), scarred uterus (24.5%), and gestational hypertension (12.4%), with no significant differences between groups (P = 0.78). Subgroup analysis further revealed that the proportion of pregnancies conceived via in vitro fertilization was slightly higher in the non-persistent group compared with the persistent group (9.5% vs. 7.5%, P = 0.62), although this difference did not reach statistical significance. Regarding fetal heart rate monitoring, the majority of cases exhibited reactive patterns (85.8%), while non-reactive patterns were slightly more frequent in the persistent group compared with the non-persistent group (4.5% vs. 3.2%, P = 0.45). Primary and Secondary Outcomes No stillbirths occurred in either group. Compared with the non-persistent low S/D group, the persistent group had a significantly shorter interval from first detection of low S/D to delivery (20.4 ± 8.7 days vs. 26.8 ± 6.5 days, P < 0.001) (Fig. 2) and lower neonatal birth weight (3312 ± 518 g vs. 3428 ± 462 g, P = 0.012) (Fig. 3). There were no statistically significant differences between groups in the rates of Apgar score < 7 at 5 minutes (0.9% vs. 1.8%, P = 0.372), NICU admission (0.2% vs. 0.5%, P = 0.625), or neonatal respiratory distress (0.9% vs. 1.8%, P = 0.372) (Table 2). The rate of umbilical cord abnormalities was higher in the persistent group compared with the non-persistent group (15.3% vs. 10.1%, P = 0.05). Subgroup analysis revealed that among cesarean deliveries, the proportion performed for fetal distress was slightly higher in the non-persistent group (18.4% vs. 14.2%, P = 0.22). The rate of low birth weight (< 2500 g) was higher in the persistent group (4.5% vs. 2.7%, P = 0.18), although this difference did not reach statistical significance. Stratified Analysis by Gestational Age at First Detection of Low S/D Stratified analysis according to gestational age at first detection of low S/D revealed that the S/D ratio progressively decreased with advancing gestational age (36–37 weeks: 2.00 → 40–41 weeks: 1.80; linear regression slope − 0.05/week, P = 0.002) (Fig. 4). Gestational age at first detection of low S/D was significantly negatively correlated with the interval to delivery (r=-0.32, P < 0.001), with greater dispersion observed in the lower gestational age group (Fig. 5). In the high gestational age stratum (40–41 weeks), the persistent low S/D subgroup had a significantly higher rate of fetal distress compared with the non-persistent subgroup (6.1% vs. 2.4%, P = 0.03). Neonatal birth weight was lowest in the persistent group within the low gestational age stratum (3156 ± 412 g), potentially reflecting the impact of early-onset abnormalities on fetal growth. Furthermore, the rate of Apgar score < 7 at 5 minutes was highest in the non-persistent group within the 36–37 weeks stratum (1.9%); however, the differences between groups were not statistically significant (P = 0.15) (Table 3). Kaplan-Meier survival analysis demonstrated a longer interval from detection to delivery in the non-persistent group, suggesting a tendency toward delayed delivery in this population (HR 1.45, 95% CI: 1.22–1.72, P < 0.001) (Fig. 6). Umbilical cord abnormalities were most prevalent in the persistent group within the high gestational age stratum (7.3%). Overall, the rate of umbilical cord abnormalities was significantly higher in the persistent group compared with the non-persistent group (15.3% vs. 10.1%, P = 0.05) (Fig. 7). Multivariable Regression Analysis Multivariable logistic regression analysis demonstrated that the pattern of low S/D alone (persistent vs. non-persistent) was not an independent predictor of adverse outcomes (OR = 1.08, 95% CI: 0.75–1.56, P = 0.68). Umbilical cord abnormalities (OR = 3.12, 95% CI: 1.89–5.15, P < 0.001) and fetal distress (OR = 4.32, 95% CI: 2.18–8.56, P 0.05). The model demonstrated good fit (Nagelkerke R²=0.28; Hosmer-Lemeshow goodness-of-fit test P = 0.45) (Table 4). Discussion This large-sample retrospective cohort study systematically compared the impact of persistent versus non-persistent low umbilical artery S/D ratios (≤ 5th percentile) on pregnancy outcomes in the third trimester, and further elucidated risk characteristics across different gestational ages through stratified analysis. Our findings demonstrated that the rate of umbilical cord abnormalities was significantly higher in the persistent low S/D group compared with the non-persistent group (15.3% vs. 10.1%, P < 0.05), with nuchal cord being the predominant type (accounting for 52.3% of cases). This finding aligns with recent research on the association between umbilical cord structural abnormalities and hemodynamic alterations [ 5 – 6 , 17 ]. A retrospective cohort study demonstrated that pregnancies complicated by nuchal cord were associated with increased risks of adverse obstetric and neonatal outcomes, including abnormal fetal heart rate patterns [ 5 ]. A comprehensive review indicated that various umbilical cord diseases, including structural abnormalities, can significantly affect obstetric and perinatal outcomes through hemodynamic changes [ 6 ]. Furthermore, abnormal umbilical artery S/D, PI, and RI were significantly higher in the adverse pregnancy outcome group compared with the normal outcome group, highlighting the close association between abnormal Doppler parameters and placental insufficiency [ 15 ]. Pearson correlation analysis confirmed a significant negative correlation between gestational age at first detection of low S/D and the interval to delivery (r=-0.32, P < 0.01), suggesting that early detection of low S/D may prompt clinicians to adopt more active management strategies. This association carries important clinical implications: early detection of low S/D provides a broader time window for clinical intervention, yet simultaneously necessitates more precise risk stratification to avoid unnecessary premature interventions. A meta-analysis incorporating studies confirmed that uterine artery PI and S/D ratios were significantly altered in the third trimester of diabetic pregnancies, indicating heterogeneity in Doppler parameter alterations across different high-risk populations and underscoring the need for comprehensive interpretation integrating gestational age and comorbid conditions [ 14 ]. As highlighted by Figueras and Gratacós in the context of fetal growth restriction, no single Doppler parameter should be used in isolation for clinical decision-making; rather, an integrated assessment incorporating multiple parameters is essential [ 22 ]. This principle is directly applicable to the interpretation of low S/D ratios: our finding that a low S/D pattern alone was not an independent predictor of adverse outcomes, whereas its combination with umbilical cord abnormalities or fetal distress significantly increased risk, underscores the necessity of a multi-parameter approach. Furthermore, the interplay between Doppler abnormalities and maternal comorbidities influences management strategies. McKinney et al. demonstrated that in pregnancies complicated by preeclampsia, the presence of fetal growth restriction significantly affects the duration of expectant management, highlighting the need for individualized risk assessment [ 23 ]. Similarly, in cases with low S/D ratios, the coexistence of additional risk factors—such as umbilical cord abnormalities or advanced gestational age—may warrant more proactive intervention, reinforcing the importance of personalized clinical judgment. Gestational age-stratified analysis further revealed risk characteristics specific to particular gestational windows: among women delivering at 40–41 weeks, the persistent low S/D subgroup exhibited a significantly higher incidence of fetal distress (6.1% vs. 2.8%, P < 0.05). This phenomenon may be attributable to diminished placental functional reserve in late pregnancy, increased risk of umbilical cord compression, or acute hemodynamic alterations [ 18 , 20 , 26 ]. A study in high-risk pregnancies demonstrated that ultrasonography and color Doppler assessments were accurate in predicting fetal outcomes, including associations with abnormal Doppler indices and perinatal complications [ 7 , 19 ]. A prospective study in pregnancies complicated by fetal growth restriction found that abnormal UA S/D was significantly associated with increased cesarean section rates, birth weight < 10th percentile, NICU admission, and neonatal complications; moreover, UA S/D demonstrated superior sensitivity and diagnostic accuracy for predicting SGA compared with UA PI [ 8 ]. Multivariable regression analysis identified umbilical cord abnormalities (OR = 3.12, 95% CI: 1.89–5.15, P < 0.001) and fetal distress (OR = 4.32, 95% CI: 2.18–8.56, P < 0.001) as independent risk factors for adverse pregnancy outcomes, consistent with the findings regarding the pathophysiological mechanisms of abnormal umbilical artery blood flow [ 9 ]. Notably, the low S/D pattern itself was not an independent predictor, suggesting that its clinical significance requires comprehensive interpretation in conjunction with other parameters—a finding that partially aligns with observations that low umbilical artery resistance may coexist with normal pregnancy outcomes [ 10 ]. Research demonstrated that, regardless of fetal weight, persistent elevation of UA S/D was significantly associated with preterm birth, increased NICU admission rates, and reduced birth weight, suggesting that the persistence pattern of S/D carries greater clinical significance than a single measurement [ 11 ]. A study proposed that the amniotic fluid-umbilical artery-middle cerebral artery combined ratio (AUCR) exhibits superior predictive performance for adverse outcomes in late-onset FGR compared with single parameters, supporting a multi-parameter integrated assessment strategy [ 12 ]. Regarding the underlying mechanisms, a low S/D ratio may reflect two distinct physiological or pathological states: first, excessive dilation of the placental vascular bed with physiologically reduced blood flow resistance; second, structural umbilical cord pathologies (such as nuchal cord or torsion) leading to localized hemodynamic alterations [ 6 , 13 , 27 , 29 ]. A scoping review noted that umbilical vascular thromboembolism is associated with high-risk factors, can result in fetal distress, FGR, and even stillbirth, with certain maternal conditions identified as contributing factors [ 13 ]. Case reports and systematic reviews have further documented the clinical significance of umbilical cord true knots and thrombosis, which may present with persistently low resistance patterns [ 24 – 25 , 28 ]. Persistent low S/D may represent a chronic compensatory state—the fetus adapts over time to a low-resistance environment but with diminished functional reserve, rendering it more susceptible to decompensation when facing stress in late pregnancy. These findings have important clinical implications: detection of low S/D in early gestational weeks (36–37 weeks) should prompt enhanced monitoring of placental function and umbilical cord structure; while persistent low S/D in late gestation (40–41 weeks) warrants heightened vigilance for umbilical cord factors, with consideration of timely delivery when indicated. This study underscores the necessity of integrating Doppler parameters with clinical indicators for comprehensive assessment, supporting the ISUOG guidelines advocating multi-parameter monitoring [ 1 – 2 ]. Compared with previous studies, the strengths of this investigation include: a relatively large sample size (1,790 cases), the use of matching design to minimize confounding bias, and the novel integration of gestational age-stratified analysis with Kaplan-Meier survival analysis to systematically distinguish between persistent and non-persistent low S/D flow patterns, thereby revealing their distinct clinical implications and providing a new perspective for refined risk stratification. Several limitations should be acknowledged. First, the retrospective design may introduce information bias, and some clinical variables were incompletely documented. Second, criteria for neonatal intensive care unit (NICU) admission may have varied among different clinicians, potentially affecting the standardization of outcome measures. Third, the relatively small sample size in the lower gestational age subgroups (e.g., 36–37 weeks) may have limited statistical power and compromised the reliability of subgroup analyses. Fourth, the single-center design restricts the generalizability of our findings. Fifth, the absence of placental histopathological examination precludes validation of the pathological basis underlying the observed hemodynamic alterations at the structural level. Future multicenter prospective studies incorporating placental histopathology, umbilical cord pathological analysis, and long-term neonatal neurodevelopmental follow-up are warranted to further elucidate the pathophysiological mechanisms underlying low S/D and to determine optimal timing for intervention and delivery strategies. Conclusions This large-sample retrospective cohort study demonstrates that persistent low S/D ratio, compared with non-persistent low S/D, is associated with a higher rate of umbilical cord abnormalities and lower neonatal birth weight. Gestational age-stratified analysis suggests that persistent low S/D at advanced gestational ages may increase the risk of fetal distress. Gestational age at first detection of low S/D was negatively correlated with the interval to delivery. Multivariable analysis indicates that low S/D ratio accompanied by umbilical cord abnormalities and fetal distress are independent predictors of adverse pregnancy outcomes. Abbreviations AUCR amniotic fluid-umbilical artery-middle cerebral artery combined ratio CI confidence interval CTG cardiotocography FGR fetal growth restriction HR hazard ratio ISUOG International Society of Ultrasound in Obstetrics and Gynecology NICU neonatal intensive care unit OR odds ratio PI pulsatility index RI resistance index S/D systolic/diastolic ratio SGA small for gestational age SPSS Statistical Package for the Social Sciences STROBE Strengthening the Reporting of Observational Studies in Epidemiology UA umbilical artery. Declarations Ethics approval and consent to participate Ethical approval was obtained (approval number: SFYWZLP2026-005). All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the Shandong Provincial Maternal and Child Health Science and Technology Project (Grant number: SFYXH-2025Y016). Authors’ contributions Qing Yuan and Liang Ding designed the study. Fudan Huang, Xiaoxiao Dong, Xia Song, and Juntao Zheng assisted in data collection and were responsible for data management. Qing Yuan and Liang Ding drafted the manuscript. Fudan Huang, Xiaoxiao Dong, and Juntao Zheng revised the manuscript. All authors have read and approved the final manuscript. (# These authors contributed equally to this work.) Acknowledgements We would like to thank all the participants and their families. References Bhide A, Acharya G, Baschat AA, et al. 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Tu P, Li X, Zhang Y, et al. Hemodynamic changes and perinatal outcome associated with umbilical artery thrombosis: a retrospective study. Orphanet J Rare Dis. 2024;19(1):123. 10.1186/s13023-024-03107-y . Romani E, De Robertis V, et al. Umbilical Artery Thrombosis: A case report of prenatal diagnosis and systematic review of the literature. Eur J Obstet Gynecol Reprod Biol. 2024;294:123–30. 10.1016/j.ejogrb.2024.01.012 . Wu XQ, Chen Y, Li X, et al. Effect of abnormal placental cord insertion on hemodynamic change of umbilical cord in a tertiary center: a prospective cohort study. Postgrad Med J. 2025;101(1193):193–200. 10.1093/postmj/qgae193 . Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9078012","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":620407730,"identity":"c34edb8d-c84b-4541-8c63-004d2faf3f0c","order_by":0,"name":"Qing Yuan","email":"","orcid":"","institution":"Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Yuan","suffix":""},{"id":620407732,"identity":"a7f90ef5-48bf-48c7-9efe-421cfeda0478","order_by":1,"name":"Liang Ding","email":"","orcid":"","institution":"Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Ding","suffix":""},{"id":620407733,"identity":"811a4f35-e84d-4de2-b39e-2ff9966576d4","order_by":2,"name":"Fudan Huang","email":"","orcid":"","institution":"Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Fudan","middleName":"","lastName":"Huang","suffix":""},{"id":620407735,"identity":"e0df099b-7b61-452b-b1a9-832fe07fc8b5","order_by":3,"name":"Xiaoxiao Dong","email":"","orcid":"","institution":"Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoxiao","middleName":"","lastName":"Dong","suffix":""},{"id":620407737,"identity":"5034479d-9ef2-4032-a946-4a95f6bb2786","order_by":4,"name":"Xia Song","email":"","orcid":"","institution":"Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Xia","middleName":"","lastName":"Song","suffix":""},{"id":620407738,"identity":"e0658b2e-a193-45bb-bc5a-efc216f67037","order_by":5,"name":"Juntao Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYBACfvb+x49/VPyT42dmPkCcFsmeM2zGDGcOGEu2syUQp8Xghg+DNGPbgcQN/TwGRLrsBu8B48K2O4wbmHk+3njDYCen20BAB+PsvoTHM849YzZn5t1sOYch2djsAAEtzDIHDAx4ypjZLJt5t0nzMBxI3EZIC5tEgoEEDxszj8FhnmfEaeGRyDGQ5mk7LAHUwkacFgmeY2mGM86kGUg2sxlbzjEgwi/2x5sPP/hQYVPfz3/44Y03FXZyBLWgWUls1CBpIVXHKBgFo2AUjAgAABQhQyLB0nkhAAAAAElFTkSuQmCC","orcid":"","institution":"Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University","correspondingAuthor":true,"prefix":"","firstName":"Juntao","middleName":"","lastName":"Zheng","suffix":""}],"badges":[],"createdAt":"2026-03-10 02:09:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9078012/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9078012/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106875893,"identity":"419c73d6-be7e-4f6b-8534-ab9f17305fcf","added_by":"auto","created_at":"2026-04-14 10:26:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1740058,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of inclusion and exclusion criteria.\u003c/p\u003e","description":"","filename":"Figure1.Flowchartofinclusionandexclusioncriteria..png","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/164002e9527e3b99a6fe06e4.png"},{"id":106875886,"identity":"fe7d9509-75a8-42ab-b3f1-6982089f4de5","added_by":"auto","created_at":"2026-04-14 10:26:56","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2268638,"visible":true,"origin":"","legend":"\u003cp\u003eBox plot comparing the interval from first detection of low S/D to delivery between the persistent and non-persistent low S/D groups. The central line represents the median, boxes indicate interquartile range (IQR), and whiskers extend to 1.5 × IQR.\u003c/p\u003e","description":"","filename":"Figure2.Boxplotofintervaltodelivery.Medianintervalwas26daysIQR1235inthenonpersistentlowSDgroupversus20daysIQR725inthepersistentgroupwithsignificantlygreatervariabilityi.png","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/b1c9bfc07e974c467d8de4e4.png"},{"id":106875945,"identity":"6179be98-6285-4106-a392-d577f94c3cf2","added_by":"auto","created_at":"2026-04-14 10:27:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2065717,"visible":true,"origin":"","legend":"\u003cp\u003eViolin plot comparing neonatal birth weight between the persistent and non-persistent low S/D groups. The shape represents the distribution of data, the white dot indicates the median, and the thick black bar represents the interquartile range.\u003c/p\u003e","description":"","filename":"Figure3.Violinplotofneonatalbirthweight.ThepersistentlowSDgroupdemonstratedoverallhigherbirthweightcomparedtothenonpersistentgroupMannWhitneyUtestP0.012..png","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/e15db5c29d944370880b55d7.png"},{"id":106875892,"identity":"b28b75bf-284c-46b9-a53c-c5365e852b72","added_by":"auto","created_at":"2026-04-14 10:26:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1625122,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot with regression line showing the trend of mean S/D ratio across gestational age at first detection of low S/D. The shaded area represents the 95% confidence interval.\u003c/p\u003e","description":"","filename":"Figure4.TrendofmeanSDratiowithgestationalage..png","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/6f2d58fe15ce68f014d6ce24.png"},{"id":106875871,"identity":"fc0fe071-3fe8-4a61-bf56-ee5c0b9ae6d9","added_by":"auto","created_at":"2026-04-14 10:26:49","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1845724,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot showing the correlation between gestational age at first detection of low S/D and the interval to delivery. The regression line with 95% confidence interval is shown (r=-0.32, P\u0026lt;0.001).\u003c/p\u003e","description":"","filename":"Figure5.Scatterplotofintervalfromdetectiontodeliverystratifiedbygestationalweek..png","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/ef98656e3f23da9cbebdf087.png"},{"id":106875819,"identity":"26882cf6-c73a-4db5-9c13-d8ddcedfb1d6","added_by":"auto","created_at":"2026-04-14 10:26:28","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":2917487,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves comparing the interval from first detection of low S/D to delivery between the persistent and non-persistent low S/D groups. The curves were compared using the log-rank test (P\u0026lt;0.001).\u003c/p\u003e","description":"","filename":"Figure6.KaplanMeiersurvivalcurveofintervalfromdetectiontodelivery.png","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/49200d799bf38dd3faf72dd5.png"},{"id":106875855,"identity":"8d3f686c-31df-4475-89f1-05931ec08fed","added_by":"auto","created_at":"2026-04-14 10:26:45","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":90412,"visible":true,"origin":"","legend":"\u003cp\u003ePie chart showing the composition of umbilical cord abnormalities (among cases with abnormalities).\u003c/p\u003e","description":"","filename":"Figure7.Piechartshowingthecompositionofumbilicalcordabnormalitiesamongcaseswithabnormalities..png","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/a61425dc19e389e90df5113a.png"},{"id":108804128,"identity":"2a389500-636a-4041-a547-e3f52ef301c0","added_by":"auto","created_at":"2026-05-08 15:16:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":11825515,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/905cf2ab-b897-4d72-8c3b-1fda4b4cfa0c.pdf"},{"id":106875825,"identity":"b1a262c7-df11-4d10-b05a-4b3f1ef0d08d","added_by":"auto","created_at":"2026-04-14 10:26:29","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24698,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-9078012/v1/3063e1af62eea925b618fdb0.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of an Umbilical Artery S/D Ratio ≤ 5th Percentile on Pregnancy Outcomes: A Retrospective Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eUmbilical artery Doppler assessment during pregnancy is a core technique for monitoring fetal well-being, with the systolic/diastolic (S/D) ratio serving as the most commonly used parameter and having been incorporated into international guidelines for high-risk pregnancy management [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Elevated S/D ratios reflect increased placental vascular resistance and are frequently associated with fetal growth restriction, hypoxia, and adverse perinatal outcomes [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, the clinical significance of a low S/D ratio (\u0026le;\u0026thinsp;5th percentile) has long been overlooked. Existing research has predominantly focused on elevated values, with few systematic investigations into the potential pathological implications of low values [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA low S/D ratio may result from placental hyperperfusion, umbilical cord structural abnormalities (such as torsion, true knot, or thrombosis), or decreased vascular resistance due to increased fetal cardiac output [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A case series reported eight cases of persistently low S/D ratios, all of which were accompanied by severe umbilical cord pathologies including thrombosis, excessive torsion, and true knot, suggesting that persistent low S/D may serve as an early warning signal for acute umbilical cord events [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Other studies have shown that low umbilical artery resistance is associated with normal pregnancy outcomes; however, these investigations were limited by small sample sizes and failed to distinguish between persistent and non-persistent patterns [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Comparative studies examining persistent versus non-persistent low S/D ratios, as well as the influence of gestational age, are even scarcer. In clinical practice, the absence of unified management guidelines for low S/D ratios often leads clinicians to regard it as a \"physiological variant,\" potentially delaying timely intervention [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study employs a large-sample, single-center retrospective cohort design to systematically compare the impact of persistent versus non-persistent low S/D ratios on perinatal outcomes, with detailed gestational age-stratified analysis. By employing multivariable regression and survival analysis, we aimed to identify independent risk factors and provide evidence-based guidance for clinical decision-making regarding low S/D ratios.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Ethics\u003c/h2\u003e \u003cp\u003e This was a single-center retrospective cohort study that included 1,790 women with singleton pregnancies who underwent umbilical artery Doppler examinations at Shandong Provincial Maternal and Child Health Care Hospital between January 2023 and December 2025. The study was approved by the Ethics Committee of Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University (approval number: SFYWZLP2026-005), and the protocol adhered to the STROBE reporting guidelines for observational studies [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria\u003c/h3\u003e\n\u003cp\u003eInclusion criteria were: gestational age\u0026thinsp;\u0026ge;\u0026thinsp;36 weeks, singleton pregnancy, and at least one complete umbilical artery S/D ratio record. Exclusion criteria included persistently elevated S/D ratios, absent or reversed end-diastolic flow; multiple pregnancies; and fetal structural or chromosomal abnormalities.\u003c/p\u003e\n\u003ch3\u003eDefinition and Grouping of S/D Ratio\u003c/h3\u003e\n\u003cp\u003eLow S/D ratio was defined as an initial measurement \u0026le;5th percentile based on the gestational age-specific reference ranges established by Acharya et al [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Persistent low S/D was defined as all measurements \u0026le;5th percentile, while non-persistent low S/D was defined as at least one, but not all, measurements \u0026le;5th percentile. A computer-generated 1:1 random algorithm was used to match the persistent and non-persistent groups according to gestational age at first detection of low S/D, resulting in 444 cases in each group to ensure baseline comparability.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eThe following variables were extracted from the electronic medical record system: maternal age, parity, comorbidities (including gestational diabetes mellitus, scarred uterus, hypertensive disorders), mode of conception, type of fetal heart rate monitoring, gestational age at first detection of low S/D, percentile value, S/D ratio, days of expectant management, gestational age at delivery, mode of delivery, umbilical cord abnormalities (such as torsion, thrombosis), neonatal birth weight, and Apgar scores. All data were independently extracted and cross-checked by two researchers.\u003c/p\u003e\n\u003ch3\u003eOutcome Measures\u003c/h3\u003e\n\u003cp\u003ePrimary outcomes included: Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 5 minutes, admission to the neonatal intensive care unit (NICU), and neonatal respiratory distress (defined by clinical diagnosis or Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 5 minutes). Secondary outcomes comprised: cesarean section rate, fetal distress (explicitly documented as indication for delivery or intraoperative finding), and the interval from first detection of low S/D to delivery (in days). Outcomes were compared after stratifying by gestational age at first detection of low S/D into two-week intervals: 36\u0026ndash;37 weeks, 38\u0026ndash;39 weeks, and 40\u0026ndash;41 weeks.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS version 26.0. Continuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and compared between groups using the independent samples t-test. Categorical variables were expressed as frequencies and percentages and compared using the chi-square test or Fisher's exact test, as appropriate. The interval from first detection of low S/D to delivery was analyzed using the Kaplan-Meier method, with survival curves generated and compared between groups using the log-rank test. Multivariable logistic regression analysis was performed to identify independent predictors of adverse outcomes (defined as Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 5 minutes or neonatal respiratory distress), with covariates including group allocation (persistent vs. non-persistent low S/D), gestational age at first detection of low S/D, umbilical cord abnormalities, fetal distress, maternal age, and maternal comorbidities. Pearson correlation analysis was used to assess the relationship between gestational age at first detection of low S/D and the interval to delivery. A two-tailed P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003eGeneral Characteristics\u003c/h2\u003e\n \u003cp\u003eAmong the 1,790 pregnant women included in the study, 1,056 had documented low S/D ratios, yielding a total of 2,125 individual measurements. Of these, 612 cases were classified as persistent low S/D and 444 as non-persistent low S/D (Fig. 1). After matching, baseline characteristics were well-balanced between the two groups (Table 1). The mean maternal age was 31.0 years, and the mean gestational age at first detection of low S/D was 37.9 weeks. The most common maternal comorbidities were gestational diabetes mellitus (22.1%), scarred uterus (24.5%), and gestational hypertension (12.4%), with no significant differences between groups (P = 0.78). Subgroup analysis further revealed that the proportion of pregnancies conceived via in vitro fertilization was slightly higher in the non-persistent group compared with the persistent group (9.5% vs. 7.5%, P = 0.62), although this difference did not reach statistical significance. Regarding fetal heart rate monitoring, the majority of cases exhibited reactive patterns (85.8%), while non-reactive patterns were slightly more frequent in the persistent group compared with the non-persistent group (4.5% vs. 3.2%, P = 0.45).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003ePrimary and Secondary Outcomes\u003c/h2\u003e\n \u003cp\u003eNo stillbirths occurred in either group. Compared with the non-persistent low S/D group, the persistent group had a significantly shorter interval from first detection of low S/D to delivery (20.4 ± 8.7 days vs. 26.8 ± 6.5 days, P \u0026lt; 0.001) (Fig. 2) and lower neonatal birth weight (3312 ± 518 g vs. 3428 ± 462 g, P = 0.012) (Fig. 3). There were no statistically significant differences between groups in the rates of Apgar score \u0026lt; 7 at 5 minutes (0.9% vs. 1.8%, P = 0.372), NICU admission (0.2% vs. 0.5%, P = 0.625), or neonatal respiratory distress (0.9% vs. 1.8%, P = 0.372) (Table 2). The rate of umbilical cord abnormalities was higher in the persistent group compared with the non-persistent group (15.3% vs. 10.1%, P = 0.05). Subgroup analysis revealed that among cesarean deliveries, the proportion performed for fetal distress was slightly higher in the non-persistent group (18.4% vs. 14.2%, P = 0.22). The rate of low birth weight (\u0026lt; 2500 g) was higher in the persistent group (4.5% vs. 2.7%, P = 0.18), although this difference did not reach statistical significance.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003eStratified Analysis by Gestational Age at First Detection of Low S/D\u003c/h2\u003e\n \u003cp\u003eStratified analysis according to gestational age at first detection of low S/D revealed that the S/D ratio progressively decreased with advancing gestational age (36–37 weeks: 2.00 → 40–41 weeks: 1.80; linear regression slope − 0.05/week, P = 0.002) (Fig. 4). Gestational age at first detection of low S/D was significantly negatively correlated with the interval to delivery (r=-0.32, P \u0026lt; 0.001), with greater dispersion observed in the lower gestational age group (Fig. 5). In the high gestational age stratum (40–41 weeks), the persistent low S/D subgroup had a significantly higher rate of fetal distress compared with the non-persistent subgroup (6.1% vs. 2.4%, P = 0.03). Neonatal birth weight was lowest in the persistent group within the low gestational age stratum (3156 ± 412 g), potentially reflecting the impact of early-onset abnormalities on fetal growth. Furthermore, the rate of Apgar score \u0026lt; 7 at 5 minutes was highest in the non-persistent group within the 36–37 weeks stratum (1.9%); however, the differences between groups were not statistically significant (P = 0.15) (Table 3). Kaplan-Meier survival analysis demonstrated a longer interval from detection to delivery in the non-persistent group, suggesting a tendency toward delayed delivery in this population (HR 1.45, 95% CI: 1.22–1.72, P \u0026lt; 0.001) (Fig. 6). Umbilical cord abnormalities were most prevalent in the persistent group within the high gestational age stratum (7.3%). Overall, the rate of umbilical cord abnormalities was significantly higher in the persistent group compared with the non-persistent group (15.3% vs. 10.1%, P = 0.05) (Fig. 7).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003eMultivariable Regression Analysis\u003c/h2\u003e\n \u003cp\u003eMultivariable logistic regression analysis demonstrated that the pattern of low S/D alone (persistent vs. non-persistent) was not an independent predictor of adverse outcomes (OR = 1.08, 95% CI: 0.75–1.56, P = 0.68). Umbilical cord abnormalities (OR = 3.12, 95% CI: 1.89–5.15, P \u0026lt; 0.001) and fetal distress (OR = 4.32, 95% CI: 2.18–8.56, P \u0026lt; 0.001) were identified as independent risk factors. Maternal age and comorbidities showed no significant associations with adverse outcomes (all P \u0026gt; 0.05). The model demonstrated good fit (Nagelkerke R²=0.28; Hosmer-Lemeshow goodness-of-fit test P = 0.45) (Table 4).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis large-sample retrospective cohort study systematically compared the impact of persistent versus non-persistent low umbilical artery S/D ratios (\u0026le;\u0026thinsp;5th percentile) on pregnancy outcomes in the third trimester, and further elucidated risk characteristics across different gestational ages through stratified analysis. Our findings demonstrated that the rate of umbilical cord abnormalities was significantly higher in the persistent low S/D group compared with the non-persistent group (15.3% vs. 10.1%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with nuchal cord being the predominant type (accounting for 52.3% of cases). This finding aligns with recent research on the association between umbilical cord structural abnormalities and hemodynamic alterations [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A retrospective cohort study demonstrated that pregnancies complicated by nuchal cord were associated with increased risks of adverse obstetric and neonatal outcomes, including abnormal fetal heart rate patterns [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. A comprehensive review indicated that various umbilical cord diseases, including structural abnormalities, can significantly affect obstetric and perinatal outcomes through hemodynamic changes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Furthermore, abnormal umbilical artery S/D, PI, and RI were significantly higher in the adverse pregnancy outcome group compared with the normal outcome group, highlighting the close association between abnormal Doppler parameters and placental insufficiency [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePearson correlation analysis confirmed a significant negative correlation between gestational age at first detection of low S/D and the interval to delivery (r=-0.32, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), suggesting that early detection of low S/D may prompt clinicians to adopt more active management strategies. This association carries important clinical implications: early detection of low S/D provides a broader time window for clinical intervention, yet simultaneously necessitates more precise risk stratification to avoid unnecessary premature interventions. A meta-analysis incorporating studies confirmed that uterine artery PI and S/D ratios were significantly altered in the third trimester of diabetic pregnancies, indicating heterogeneity in Doppler parameter alterations across different high-risk populations and underscoring the need for comprehensive interpretation integrating gestational age and comorbid conditions [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. As highlighted by Figueras and Gratac\u0026oacute;s in the context of fetal growth restriction, no single Doppler parameter should be used in isolation for clinical decision-making; rather, an integrated assessment incorporating multiple parameters is essential [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This principle is directly applicable to the interpretation of low S/D ratios: our finding that a low S/D pattern alone was not an independent predictor of adverse outcomes, whereas its combination with umbilical cord abnormalities or fetal distress significantly increased risk, underscores the necessity of a multi-parameter approach. Furthermore, the interplay between Doppler abnormalities and maternal comorbidities influences management strategies. McKinney et al. demonstrated that in pregnancies complicated by preeclampsia, the presence of fetal growth restriction significantly affects the duration of expectant management, highlighting the need for individualized risk assessment [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Similarly, in cases with low S/D ratios, the coexistence of additional risk factors\u0026mdash;such as umbilical cord abnormalities or advanced gestational age\u0026mdash;may warrant more proactive intervention, reinforcing the importance of personalized clinical judgment.\u003c/p\u003e \u003cp\u003eGestational age-stratified analysis further revealed risk characteristics specific to particular gestational windows: among women delivering at 40\u0026ndash;41 weeks, the persistent low S/D subgroup exhibited a significantly higher incidence of fetal distress (6.1% vs. 2.8%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This phenomenon may be attributable to diminished placental functional reserve in late pregnancy, increased risk of umbilical cord compression, or acute hemodynamic alterations [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. A study in high-risk pregnancies demonstrated that ultrasonography and color Doppler assessments were accurate in predicting fetal outcomes, including associations with abnormal Doppler indices and perinatal complications [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. A prospective study in pregnancies complicated by fetal growth restriction found that abnormal UA S/D was significantly associated with increased cesarean section rates, birth weight \u0026lt;\u0026thinsp;10th percentile, NICU admission, and neonatal complications; moreover, UA S/D demonstrated superior sensitivity and diagnostic accuracy for predicting SGA compared with UA PI [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultivariable regression analysis identified umbilical cord abnormalities (OR\u0026thinsp;=\u0026thinsp;3.12, 95% CI: 1.89\u0026ndash;5.15, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and fetal distress (OR\u0026thinsp;=\u0026thinsp;4.32, 95% CI: 2.18\u0026ndash;8.56, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as independent risk factors for adverse pregnancy outcomes, consistent with the findings regarding the pathophysiological mechanisms of abnormal umbilical artery blood flow [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Notably, the low S/D pattern itself was not an independent predictor, suggesting that its clinical significance requires comprehensive interpretation in conjunction with other parameters\u0026mdash;a finding that partially aligns with observations that low umbilical artery resistance may coexist with normal pregnancy outcomes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Research demonstrated that, regardless of fetal weight, persistent elevation of UA S/D was significantly associated with preterm birth, increased NICU admission rates, and reduced birth weight, suggesting that the persistence pattern of S/D carries greater clinical significance than a single measurement [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A study proposed that the amniotic fluid-umbilical artery-middle cerebral artery combined ratio (AUCR) exhibits superior predictive performance for adverse outcomes in late-onset FGR compared with single parameters, supporting a multi-parameter integrated assessment strategy [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding the underlying mechanisms, a low S/D ratio may reflect two distinct physiological or pathological states: first, excessive dilation of the placental vascular bed with physiologically reduced blood flow resistance; second, structural umbilical cord pathologies (such as nuchal cord or torsion) leading to localized hemodynamic alterations [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. A scoping review noted that umbilical vascular thromboembolism is associated with high-risk factors, can result in fetal distress, FGR, and even stillbirth, with certain maternal conditions identified as contributing factors [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Case reports and systematic reviews have further documented the clinical significance of umbilical cord true knots and thrombosis, which may present with persistently low resistance patterns [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Persistent low S/D may represent a chronic compensatory state\u0026mdash;the fetus adapts over time to a low-resistance environment but with diminished functional reserve, rendering it more susceptible to decompensation when facing stress in late pregnancy. These findings have important clinical implications: detection of low S/D in early gestational weeks (36\u0026ndash;37 weeks) should prompt enhanced monitoring of placental function and umbilical cord structure; while persistent low S/D in late gestation (40\u0026ndash;41 weeks) warrants heightened vigilance for umbilical cord factors, with consideration of timely delivery when indicated. This study underscores the necessity of integrating Doppler parameters with clinical indicators for comprehensive assessment, supporting the ISUOG guidelines advocating multi-parameter monitoring [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Compared with previous studies, the strengths of this investigation include: a relatively large sample size (1,790 cases), the use of matching design to minimize confounding bias, and the novel integration of gestational age-stratified analysis with Kaplan-Meier survival analysis to systematically distinguish between persistent and non-persistent low S/D flow patterns, thereby revealing their distinct clinical implications and providing a new perspective for refined risk stratification. Several limitations should be acknowledged. First, the retrospective design may introduce information bias, and some clinical variables were incompletely documented. Second, criteria for neonatal intensive care unit (NICU) admission may have varied among different clinicians, potentially affecting the standardization of outcome measures. Third, the relatively small sample size in the lower gestational age subgroups (e.g., 36\u0026ndash;37 weeks) may have limited statistical power and compromised the reliability of subgroup analyses. Fourth, the single-center design restricts the generalizability of our findings. Fifth, the absence of placental histopathological examination precludes validation of the pathological basis underlying the observed hemodynamic alterations at the structural level. Future multicenter prospective studies incorporating placental histopathology, umbilical cord pathological analysis, and long-term neonatal neurodevelopmental follow-up are warranted to further elucidate the pathophysiological mechanisms underlying low S/D and to determine optimal timing for intervention and delivery strategies.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis large-sample retrospective cohort study demonstrates that persistent low S/D ratio, compared with non-persistent low S/D, is associated with a higher rate of umbilical cord abnormalities and lower neonatal birth weight. Gestational age-stratified analysis suggests that persistent low S/D at advanced gestational ages may increase the risk of fetal distress. Gestational age at first detection of low S/D was negatively correlated with the interval to delivery. Multivariable analysis indicates that low S/D ratio accompanied by umbilical cord abnormalities and fetal distress are independent predictors of adverse pregnancy outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAUCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eamniotic fluid-umbilical artery-middle cerebral artery combined ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCTG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiotocography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFGR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efetal growth restriction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehazard ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eISUOG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Society of Ultrasound in Obstetrics and Gynecology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eneonatal intensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eodds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulsatility index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eresistance index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eS/D\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esystolic/diastolic ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esmall for gestational age\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSPSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStatistical Package for the Social Sciences\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTROBE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStrengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eumbilical artery.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained (approval number: SFYWZLP2026-005). All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Shandong Provincial Maternal and Child Health Science and Technology Project (Grant number: SFYXH-2025Y016).\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors\u0026rsquo; contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQing Yuan and Liang Ding designed the study. Fudan Huang, Xiaoxiao Dong, Xia Song, and Juntao Zheng assisted in data collection and were responsible for data management. Qing Yuan and Liang Ding drafted the manuscript. Fudan Huang, Xiaoxiao Dong, and Juntao Zheng revised the manuscript. All authors have read and approved the final manuscript. (# These authors contributed equally to this work.)\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank all the participants and their families.\u003c/p\u003e\n"},{"header":"References ","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBhide A, Acharya G, Baschat AA, et al. ISUOG Practice Guidelines (updated): use of Doppler velocimetry in obstetrics. 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Effect of abnormal placental cord insertion on hemodynamic change of umbilical cord in a tertiary center: a prospective cohort study. Postgrad Med J. 2025;101(1193):193\u0026ndash;200. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/postmj/qgae193\u003c/span\u003e\u003cspan address=\"10.1093/postmj/qgae193\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Umbilical artery, S/D ratio, Low blood flow resistance, Perinatal outcomes, Fetal distress, Umbilical cord abnormalities, Gestational age stratification","lastPublishedDoi":"10.21203/rs.3.rs-9078012/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9078012/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate the impact of persistent versus non-persistent umbilical artery S/D ratios at or below the 5th percentile on pregnancy outcomes, and to explore its predictive value for adverse pregnancy outcomes through gestational age-stratified analysis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e This was a single-center retrospective cohort study that included 1,790 singleton pregnant women who underwent umbilical artery Doppler examinations at Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University between January 2023 and December 2025. Inclusion criteria were: gestational age\u0026thinsp;\u0026ge;\u0026thinsp;36 weeks and complete S/D ratio records. Exclusion criteria included persistently elevated S/D ratios, absent or reversed end-diastolic flow; multiple pregnancies; and fetal structural or chromosomal abnormalities. Low S/D ratio was defined as an initial measurement \u0026le;5th percentile. Persistent low S/D was defined as all measurements \u0026le;5th percentile, while non-persistent low S/D was defined as only some measurements meeting this criterion. After random 1:1 matching by gestational age, 444 cases were included in each group. Multivariable logistic regression analysis was performed to examine the role of umbilical cord abnormalities, fetal distress, neonatal birth weight, and maternal comorbidities. Primary outcomes included Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 5 minutes, admission to neonatal intensive care unit (NICU), and neonatal respiratory distress. Secondary outcomes comprised mode of delivery, fetal distress rate, and the interval from first detection of low S/D to delivery. Outcomes were compared after stratifying by the gestational age at first detection of low S/D into two-week intervals (36\u0026ndash;37, 38\u0026ndash;39, and 40\u0026ndash;41 weeks).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 1,790 included cases, 1,056 had documented low S/D ratios (based on 2,125 total measurements), comprising 612 cases in the persistent group and 444 in the non-persistent group. After matching, 444 cases were included in each group. No stillbirths occurred in either group. Compared with the non-persistent group, the persistent group had a shorter interval from detection to delivery (20.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7 days vs. 26.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5 days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and lower neonatal birth weight (3312\u0026thinsp;\u0026plusmn;\u0026thinsp;518 g vs. 3428\u0026thinsp;\u0026plusmn;\u0026thinsp;462 g, P\u0026thinsp;=\u0026thinsp;0.012). There were no statistically significant differences between groups in the rates of Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 5 minutes, NICU admission, or neonatal respiratory distress. The rate of umbilical cord abnormalities was higher in the persistent group (15.3% vs. 10.1%, P\u0026thinsp;=\u0026thinsp;0.05). Stratified analysis revealed that among the 40\u0026ndash;41 weeks group, the persistent low S/D subgroup had a higher rate of fetal distress (6.1% vs. 2.4%). Gestational age at first detection of low S/D was negatively correlated with the interval to delivery (r=-0.32, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariable logistic regression analysis demonstrated that the pattern of low S/D (persistent vs. non-persistent) was not an independent predictor (OR\u0026thinsp;=\u0026thinsp;1.08, 95% CI: 0.75\u0026ndash;1.56, P\u0026thinsp;=\u0026thinsp;0.68); however, umbilical cord abnormalities (OR\u0026thinsp;=\u0026thinsp;3.12, 95% CI: 1.89\u0026ndash;5.15, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and fetal distress (OR\u0026thinsp;=\u0026thinsp;4.32, 95% CI: 2.18\u0026ndash;8.56, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were identified as independent risk factors.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis large-sample retrospective cohort study demonstrates that persistent low S/D ratio, compared with non-persistent low S/D, is associated with a higher rate of umbilical cord abnormalities. Gestational age-stratified analysis suggests that persistent low S/D at advanced gestational ages may increase the risk of fetal distress. Gestational age at first detection of low S/D was negatively correlated with the interval to delivery. Multivariable analysis indicates that low S/D ratio accompanied by umbilical cord abnormalities and fetal distress are independent predictors of adverse pregnancy outcomes.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003enot applicable.\u003c/p\u003e","manuscriptTitle":"Impact of an Umbilical Artery S/D Ratio ≤ 5th Percentile on Pregnancy Outcomes: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 10:23:58","doi":"10.21203/rs.3.rs-9078012/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f017b08b-7f50-480a-aeb7-aa1d8f180d4e","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-04T06:11:40+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T06:26:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 10:23:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9078012","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9078012","identity":"rs-9078012","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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