Fetal Renal Artery Doppler Assessment in Early-Onset Fetal Growth Restriction and Its Association With Perinatal Outcomes: A Prospective Cohort Study

Fetal Renal Artery Doppler Assessment in Early-Onset Fetal Growth Restriction and Its Association With Perinatal Outcomes: A Prospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Fetal Renal Artery Doppler Assessment in Early-Onset Fetal Growth Restriction and Its Association With Perinatal Outcomes: A Prospective Cohort Study Indah Kurniawati, Yudianto Budi Saroyo, Muhammad Adya Firmansha Dilmy, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9068763/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality. Chronic fetal hypoxia in FGR leads to redistribution of fetal circulation, prioritizing vital organs such as the brain while reducing perfusion to peripheral organs including the kidneys. Doppler assessment of the fetal renal artery may therefore reflect peripheral vascular resistance and potentially predict adverse perinatal outcomes. Methods Prospective observational cohort study conducted at Dr. Cipto Mangunkusumo National Hospital, Jakarta (October 2025–February 2026). Doppler measurements of fetal renal artery pulsatility index (PI) and resistance index (RI) were obtained. Results A total of 60 participants were included (30 early‑onset FGR and 30 controls). Renal artery RI was significantly higher in early‑onset FGR (p = 0.026). PI did not differ significantly between groups (p = 0.167). No significant association was found between renal Doppler parameters and perinatal outcomes. Conclusion Renal artery RI is increased in early‑onset FGR, suggesting increased peripheral vascular resistance. However, renal Doppler parameters were not significantly associated with perinatal outcomes. Fetal growth restriction Renal artery Doppler Pulsatility index Resistance index Perinatal outcome Background Fetal growth restriction (FGR) is a major obstetric complication associated with increased perinatal morbidity and mortality worldwide. It affects approximately 5–10% of pregnancies and represents one of the leading causes of stillbirth and neonatal complications. In addition to short-term neonatal morbidity, FGR has been associated with long-term risks such as cardiovascular disease, hypertension, and chronic kidney disease later in life. The most common underlying mechanism of FGR is placental insufficiency, which results in chronic fetal hypoxia and reduced nutrient supply. In response to hypoxia, the fetus undergoes circulatory redistribution, commonly known as the brain-sparing effect, in which blood flow is preferentially directed toward vital organs such as the brain and heart while perfusion to peripheral organs is reduced. One of the organs affected by this redistribution is the fetal kidney, which plays an important role in maintaining fetal fluid balance and renal development. Doppler velocimetry is widely used to evaluate fetal hemodynamics in pregnancies complicated by FGR. Current clinical practice primarily focuses on Doppler assessment of the umbilical artery, middle cerebral artery, and ductus venosus to evaluate placental function and fetal adaptation to hypoxia. However, peripheral vessels such as the fetal renal artery may also provide important information regarding systemic vascular resistance and redistribution of fetal circulation. Despite the potential physiological relevance of renal circulation in FGR, studies evaluating fetal renal artery Doppler parameters remain limited and their association with perinatal outcomes has not been clearly established. Therefore, this study aimed to evaluate fetal renal artery blood flow using Doppler ultrasound in pregnancies complicated by early-onset fetal growth restriction and to investigate its relationship with perinatal outcomes. Methods Study design and setting This study was an observational analytic study with a prospective cohort design. The research was conducted at the Fetomaternal Clinic, operating theater, and Neonatal Intensive Care Unit (NICU) of Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia. Data collection was performed between October 2025 and February 2026. The study aimed to evaluate fetal renal artery Doppler indices in pregnancies complicated by early-onset fetal growth restriction (FGR) and to assess their association with perinatal outcomes. Participants The study population consisted of pregnant women in the third trimester attending the Fetomaternal Clinic during the study period. Participants were divided into two groups, case group (pregnancies diagnosed with early-onset fetal growth restriction) and control group (pregnancies with normal fetal growth). All eligible women were recruited consecutively after providing written informed consent. Eligibility criteria Inclusion criteria Case group’s inclusion criteria were singleton live fetus, gestational age between 28 and 40 weeks, and diagnosis of early-onset fetal growth restriction (< 32 weeks of gestation). For control group were singleton live fetus, gestational age between 28 and 40 weeks, and normal fetal growth according to gestational age. Sample size Based on the calculation of sample size for correlation analysis, where α = 0.05 (type I error), β = 0.20 (power 80%), and the expected correlation coefficient was 0.5. The minimum required sample size was 24 participants per group. To account for potential dropouts, an additional 25% was added, resulting in 30 participants in each group. Therefore, a total of 60 participants were included in this study. Sampling technique Participants were recruited using consecutive sampling, in which all pregnant women meeting the inclusion criteria during the study period were included until the required sample size was achieved. Clinical and research data were recorded in a digital case report form and subsequently tabulated using Microsoft Excel 365 before statistical analysis. Doppler ultrasound assessment Fetal renal artery Doppler examinations were performed using obstetric ultrasonography equipment by a trained examiner. The examination was performed with the patient in a semi-recumbent position. The ultrasound probe was used to obtain a sagittal view of the fetal body, and the ultrasound beam was directed laterally to the vertebral column to obtain a coronal section of the fetal kidneys and descending aorta. Color Doppler was used to identify the renal artery entering the kidney. A pulsed Doppler sample gate measuring 2–3 mm was placed at the center of the renal artery lumen. The Doppler parameters were optimized as follows high-pass filter: 30–60 Hz, angle of insonation: as close as possible to 0° (not exceeding 30°), gain and wall filter adjusted appropriately and pulse repetition frequency adjusted for low-velocity flow Measurements were performed when the fetus was at rest and without fetal breathing movements. At least three consecutive waveforms were recorded, and each measurement was repeated twice. The mean value was used for analysis. Measurements were obtained from the renal artery with the best visualization (either right or left side). All Doppler examinations were performed by a single operator to minimize interobserver variability. Doppler parameters The following Doppler indices were recorded Pulsatility Index (PI) = (S-D)/TAMX. and Resistance Index (RI) = (S-D)/S, where S is peak systolic velocity (PSV), D is End-diastolic velocity (EDV), and TAMX is Time-averaged maximum velocity. Umbilical cord blood gas analysis Umbilical arterial blood samples were collected immediately after delivery. The umbilical cord was clamped at two points approximately 10–20 cm from the neonate, and arterial blood was drawn using a heparinized syringe. Approximately 0.5–1 mL of blood was obtained from the umbilical artery while avoiding air bubbles. Samples were analyzed within 15 minutes using a point-of-care blood gas analyzer (i-STAT system). The parameters analyzed included umbilical arterial pH and base excess (BE). Fetal acidemia was defined as umbilical arterial pH < 7.00 and base excess ≤ − 12 mmol/L Data collection All clinical and Doppler data were recorded in standardized case report forms and subsequently entered into Microsoft Excel for data management. Neonatal outcome data were obtained from hospital medical records. Statistical analysis Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 27.0. Categorical variables were presented as frequencies and percentages, whereas continuous variables were presented as mean ± standard deviation or median with interquartile range, depending on data distribution. Normality of the data was assessed using the Shapiro–Wilk test. Comparisons between the early-onset FGR group and the control group were performed using the Mann–Whitney U test for non-normally distributed data. The association between renal artery Doppler indices and perinatal outcomes (Apgar score, NICU admission, and fetal acidemia) was evaluated using Spearman correlation analysis. A p-value < 0.05 was considered statistically significant. Ethical approval This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (approval number: KET-1357/UN2.F1/ETIK.PPM.00.02/2025). Written informed consent was obtained from all participants prior to enrollment. Participant confidentiality was maintained throughout the study, and all data were anonymized before analysis. Results Study population A total of 60 pregnant women were included in this prospective observational study conducted at the Fetal Medicine Clinic of Cipto Mangunkusumo National Referral Hospital between October 2025 and February 2026. The study population consisted of two groups: 30 women with early-onset fetal growth restriction (FGR) and 30 women with normal singleton pregnancies serving as the control group. All recruited participants fulfilled the inclusion criteria and had complete maternal, Doppler, and neonatal outcome data available for analysis. No subjects were excluded due to missing neonatal outcome parameters. Maternal and neonatal characteristics The baseline characteristics of the study population are summarized in Table 1. In both groups, the majority of participants were multiparous (53.3%), while 46.7% were primiparous. The mean maternal age in the early-onset FGR group was 28.97 years (median 27.5 years), whereas in the control group the mean maternal age was slightly higher at 30.73 years (median 31.5 years). Pregnancies complicated by early-onset FGR were delivered at an earlier gestational age compared with normal pregnancies. The mean gestational age at delivery in the FGR group was 35.7 weeks (median 37.0 weeks), while in the control group it was 37.46 weeks (median 38.0 weeks). Neonatal birth weight differed substantially between groups. The mean birth weight in the early-onset FGR group was 1,925 g (median 2,120 g), whereas the control group had a significantly higher mean birth weight of 3,014 g (median 2,900 g). All neonates in the early-onset FGR group were categorized as small for gestational age (SGA), accounting for 100% of cases. In contrast, the majority of neonates in the control group were appropriate for gestational age (AGA) (96.7%), while one neonate (3.3%) was classified as large for gestational age (LGA). Most neonates in both groups had satisfactory APGAR scores at 5 minutes. In the early-onset FGR group, 26 neonates (86.7%) had APGAR scores ≥7, while 4 neonates (13.3%) had APGAR scores <7. In the control group, almost all neonates had APGAR scores ≥7 (96.7%), and only one neonate (3.3%) had an APGAR score below 7. The mean APGAR score at 5 minutes was slightly lower in the FGR group (mean 8.3; median 9.0) compared with the control group (mean 9.1; median 9.0). Neonatal intensive care unit (NICU) admission was more common among neonates in the early-onset FGR group. Fourteen neonates (46.7%) required NICU admission, while 16 neonates (53.3%) did not require intensive care. In contrast, only two neonates (6.7%) in the control group required NICU admission, while the majority (93.3%) did not require intensive care. These findings demonstrate that pregnancies complicated by early-onset FGR were associated with a substantially higher need for neonatal intensive care. Table 1. Maternal and Neonatal Characteristics a Numerical data with normal distribution are presented as Mean ± standard deviation b Numerical data with abnormal distribution are presented as Median (Minimum-maximum) Distribution of renal artery Doppler parameters Prior to comparative analysis, the distribution of the Doppler variables was assessed using the Shapiro–Wilk normality test. The histogram of pulsatility index (PI) and resistance index (RI) demonstrated a unimodal distribution pattern without extreme skewness. However, statistical testing showed that several variables were not normally distributed. For the pulsatility index: early-onset FGR group: p = 0.041 (non-normal distribution) and control group: p = 0.095 (normal distribution). For the resistance index: early-onset FGR group: p = 0.002 (non-normal distribution) and control group: p = 0.066 (normal distribution). Because the Doppler parameters in the early-onset FGR group were not normally distributed, non-parametric statistical tests (Mann–Whitney test) were used to compare Doppler parameters between groups. Comparison of renal artery Doppler parameters between groups The comparison of fetal renal artery Doppler parameters between the early-onset FGR group and the control group is shown in Table 2. Table 2. Comparison of renal artery Doppler between groups a Mann-Whitney test. Data are presented as Median (Minimum-Maximum), Statistical significance was defined as p-value <0.05. Pulsatility Index (PI) The median pulsatility index differed slightly between the two groups, with a median difference of approximately 0.005. However, the Mann–Whitney test showed that this difference was not statistically significant (p = 0.167). This finding indicates that the pulsatility index of the fetal renal artery did not differ significantly between pregnancies complicated by early-onset FGR and normal pregnancies. Resistance Index (RI) In contrast, the resistance index showed a statistically significant difference between groups. The median resistance index differed by approximately 0.003 between the early-onset FGR group and the control group. Statistical analysis using the Mann–Whitney test demonstrated a significant difference between the two groups (p = 0.026). These results suggest that the resistance index of the fetal renal artery may better reflect alterations in peripheral vascular resistance associated with early-onset FGR compared with the pulsatility index. Association between renal artery Doppler parameters and perinatal outcomes in early-onset FGR Further analysis was performed to evaluate the relationship between fetal renal artery Doppler indices and perinatal outcomes among pregnancies complicated by early-onset FGR. The outcomes assessed included APGAR score at 5 minutes, NICU admission, umbilical artery pH, base excess (BE). Comparisons were conducted using the Mann–Whitney test. APGAR score The analysis showed no statistically significant association between renal artery Doppler indices and APGAR score at 5 minutes. Both pulsatility index and resistance index values were similar between neonates with APGAR scores <7 and those with scores ≥7, indicating that renal artery Doppler parameters were not predictive of low APGAR score in this cohort. NICU admission Similarly, no statistically significant association was found between renal artery Doppler parameters and NICU admission. Although neonates requiring NICU admission tended to have slightly different Doppler values, these differences did not reach statistical significance. Umbilical artery pH Analysis of umbilical artery pH also demonstrated no significant correlation with renal artery pulsatility index or resistance index. Neonates with lower pH values did not exhibit significantly different renal artery Doppler indices compared with those with normal pH levels. Base excess No statistically significant relationship was found between renal artery Doppler indices and base excess values. Although neonates with metabolic acidosis tended to show lower Doppler index values, the differences were not statistically significant. Overall, this study demonstrated that fetal renal artery resistance index differed significantly between early-onset FGR and normal pregnancies, suggesting increased peripheral vascular resistance in FGR, Fetal renal artery pulsatility index did not show a significant difference between groups, Renal artery Doppler parameters were not significantly associated with short-term neonatal outcomes, including APGAR score, NICU admission, umbilical artery pH, or base excess. These findings suggest that while renal artery Doppler may reflect systemic hemodynamic adaptation in early-onset FGR, its ability to predict immediate perinatal outcomes may be limited. Table 3. Association between Renal Artery Doppler and Neonatal Outcomes in Early Onset FGR *Mann-Whitney test. Statistical significance was defined as p-value <0.05 Additional analyses (Umbilical artery / Middle cerebral artery comparison and ROC–AUC) To contextualize fetal renal artery Doppler findings against established placental and cerebral Doppler parameters, we compared the discriminative performance of renal artery indices with umbilical artery Doppler measures in predicting neonatal acidemia. Receiver operating characteristic (ROC) curve analysis (picture 1) showed that Doppler parameters reflecting placental resistance, particularly the umbilical artery systolic/diastolic ratio (UA S/D) and umbilical artery pulsatility index (UA PI), had better discriminative ability for predicting umbilical cord arterial pH than renal artery Doppler parameters. The area under the ROC curve (AUC) for UA S/D was 0.884 (p = 0.008), and the AUC for UA PI was 0.812 (p = 0.030), indicating good predictive performance for identifying neonates with abnormal cord pH (table 3). In contrast, fetal renal artery PI and RI did not demonstrate statistically significant discriminatory performance for neonatal outcomes such as acidemia, low 5-minute Apgar score, need for respiratory support, or NICU admission. Tabel 3. Area Under the Curve (AUC) of Doppler Parameters for Predicting Perinatal Outcomes *Nonparametric test; true area = 0.5. UA (umbilical artery), SD (S/D ratio), MCA (mid cerebral artery), RA (Renal artery) These findings support the concept that Doppler markers of placental impedance (umbilical artery indices) are more closely linked to acute acid–base status at birth than peripheral organ Doppler indices, which may reflect earlier or more indirect adaptive responses Discussion Interpretation of renal artery Doppler findings in early-onset FGR The present study demonstrated that the fetal renal artery resistance index (RI) was significantly higher in pregnancies complicated by early-onset fetal growth restriction (FGR) compared with normal pregnancies, whereas the pulsatility index (PI) did not show a statistically significant difference. This finding suggests that early-onset FGR is associated with increased peripheral vascular resistance, which may reflect adaptive hemodynamic changes in response to chronic fetal hypoxia. Placental insufficiency is the most common underlying mechanism of early-onset FGR and results in a chronic reduction in oxygen and nutrient delivery to the fetus. In response to hypoxemia, the fetus undergoes circulatory redistribution to preserve oxygen supply to vital organs such as the brain, myocardium, and adrenal glands. This adaptive response, commonly known as the brain-sparing effect, is characterized by vasodilation of cerebral vessels and vasoconstriction of peripheral circulation. As a consequence, blood flow to non-essential organs, including the kidneys, decreases. Reduced renal perfusion leads to increased vascular resistance within the renal artery, which can be detected by Doppler ultrasound as elevated resistance index values. The renal circulation plays an important role in fetal hemodynamic adaptation. Previous physiological studies have demonstrated that renal blood flow may decrease by up to 25–50% in fetuses exposed to chronic hypoxia. Activation of the fetal sympathetic nervous system contributes to vasoconstriction of peripheral vessels, including the renal artery. This mechanism increases diastolic vascular resistance and consequently elevates Doppler indices such as RI. Therefore, the higher RI observed in the FGR group in the present study likely reflects the systemic peripheral vasoconstriction that occurs during fetal adaptation to placental insufficiency. However, the clinical utility of renal artery Doppler remains controversial. Unlike umbilical artery or cerebroplacental Doppler indices, renal artery Doppler is not routinely included in current fetal surveillance guidelines. This is partly due to the limited number of studies evaluating its predictive value and the variability in measurement techniques across studies. The findings of the present study support the hypothesis that renal artery resistance increases in early-onset FGR as part of the fetal adaptive response to hypoxia. However, the absence of a significant association with neonatal outcomes suggests that renal artery Doppler may have limited value as an isolated predictor of perinatal morbidity. Clinical implications From a clinical perspective, the assessment of renal artery Doppler may provide additional insight into the systemic hemodynamic adaptation occurring in fetuses affected by placental insufficiency. Increased renal vascular resistance may reflect the redistribution of blood flow away from peripheral organs toward vital structures. Although this parameter may not independently predict neonatal outcomes, it may contribute to a more comprehensive understanding of fetal physiology in complicated pregnancies. Future research should explore the role of renal artery Doppler in combination with other established Doppler parameters, such as the umbilical artery, middle cerebral artery, and cerebroplacental ratio. A multimodal Doppler approach may improve the ability to identify fetuses at risk of deterioration and optimize the timing of delivery. Strengths and limitations From a clinical perspective, the assessment of renal artery Doppler may provide additional insight into the systemic hemodynamic adaptation occurring in fetuses affected by placental insufficiency. Increased renal vascular resistance may reflect the redistribution of blood flow away from peripheral organs toward vital structures. Although this parameter may not independently predict neonatal outcomes, it may contribute to a more comprehensive understanding of fetal physiology in complicated pregnancies. Future research should explore the role of renal artery Doppler in combination with other established Doppler parameters, such as the umbilical artery, middle cerebral artery, and cerebroplacental ratio. A multimodal Doppler approach may improve the ability to identify fetuses at risk of deterioration and optimize the timing of delivery. Conclusion Fetal renal artery Doppler assessment provides insight into peripheral circulatory adaptation in pregnancies complicated by early-onset fetal growth restriction (FGR). In this study, the renal artery resistance index (RI) was significantly higher in early-onset FGR compared with normal pregnancies, indicating increased peripheral vascular resistance as part of the fetal response to chronic placental insufficiency. However, renal artery Doppler parameters were not significantly associated with short-term perinatal outcomes, including the 5-minute Apgar score, neonatal intensive care unit (NICU) admission, or fetal acidemia. These findings suggest that while renal artery Doppler reflects fetal hemodynamic adaptation, it has limited predictive value when used as a single parameter for adverse neonatal outcomes. Incorporating renal artery Doppler with established fetal Doppler indices may enhance the overall assessment of fetal circulatory status in early-onset FGR. Further research with larger cohorts is needed to clarify its clinical utility. Abbreviations FGR Fetal Growth Restriction PI Pulsatility Index RI Resistance Index NICU Neonatal Intensive Care Unit Declarations Ethics and consent to participate This study was approved by Ethics Committee Faculty of Medicine Universitas Indonesia (KET‑1357/UN2.F1/ETIK.PPM.00.02/2025). Written informed consent was obtained from all pregnant women prior to participation. Author contribution IK conceived the study, collected data, performed analysis, and wrote the manuscript. Conflict of interest The author declares no competing interests. Funding No external funding was received. Consent for Publication Not applicable Data availability The dataset generated and/or analyzed during the current study are not publicity available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request. References Lees CC, Stampalija T, Baschat AA, Da Silva Costa F, Ferrazzi E, Figueras F, et al. ISUOG Practice Guidelines: diagnosis and management of small-for‐gestational‐age fetus and fetal growth restriction. Ultrasound Obstet Gynecol. 2020;56(2):298–312. Melamed N, Baschat A, Yinon Y, Athanasiadis A, Mecacci F, Figueras F, et al. FIGO initiative on fetal growth: Best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynecol Obstet. 2021;152(S1):3–57. Morris RK, Johnstone E, Lees C, Morton V, Smith G, the Royal College of Obstetricians and Gynaecologists. Investigation and Care of a Small-for‐Gestational‐ Age Fetus and a Growth Restricted Fetus. BJOG [Internet]. 2024 Aug [cited 2025 Jul 1];131(9). Available from: https://obgyn.onlinelibrary.wiley.com/doi/ 10.1111/1471- 0528.17814 Perkumpulan Obstetri dan Ginekologi Indonesia HKFM (HKFM). Pedoman Nasional Pelayanan Kedokteran:Pengelolaan Kehamilan dengan Pertumbuhan Janin Terhambat. Jakarta: POGI; 2016. Armengaud JB, Yzydorczyk C, Siddeek B, Peyter AC, Simeoni U. Intrauterine growth restriction: Clinical consequences on health and disease at adulthood. Reprod Toxicol. 2021;99:168–76. Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure: Consensus definition of FGR. Ultrasound Obstet Gynecol. 2016;48(3):333–9. Sharma D, Shastri S, Sharma P. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects. Clin Med Insights Pediatr. 2016;10:CMPed.S40070. Nardozza LMM, Araujo Júnior E, Rizzo G, Deter RL, editors. Fetal Growth Restriction: Current Evidence and Clinical Practice.Cham:Springer; 2019. Available from: http://link.springer.com/ 10.1007/978-3-030-00051-6 Kamphof HD, Posthuma S, Gordijn SJ, Ganzevoort W. Fetal Growth Restriction: Mechanisms, Epidemiology, and Management. Matern Fetal Med. 2022;4(3):186–96. Zafra R, Conway L, Solomon N. Prognostic Value of Doppler Ultrasound in Triplets Conceived by In Vitro Fertilization: A Case Report and Review of the Literature. J Investig Med High Impact Case Rep. 2019;7:2324709619864131. Braga M, Moleiro ML, Guedes-Martins L. Clinical Significance of Ductus Venosus Waveform as Generated by Pressure- volume Changes in the Fetal Heart. Curr Cardiol Rev. 2019;15(3):167–76. Maulik D, Lees CC, editors. Doppler Ultrasound in Obstetrics and Gynecology [Internet]. 3rd ed. Cham: Springer; 2023. Available from: https://link.springer.com/ 10.1007/978-3-031-06189-9 El Manshy KM, Elewa A, El Sherbeiny MF, El Sayed AM. Abnormal fetal Renal Artery Doppler. Benha J Appl Sci. 2022;7(8):91–8. Pravinchandra Ahya R, Unni J. Cross Sectional Study To Assess Perinatal Outcome Of Intrauterine Growth Restriction Babies Delivered In Jehangir Hospital, Pune, Maharashtra. Int J Life Sci Biotechnol Pharma Res. 2023;12(3):1889–992. Additional Declarations No competing interests reported. Supplementary Files Informedconsent.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 09 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers invited by journal 09 Apr, 2026 Editor invited by journal 30 Mar, 2026 Editor assigned by journal 30 Mar, 2026 Submission checks completed at journal 30 Mar, 2026 First submitted to journal 09 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-9068763","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":621431350,"identity":"f5c6a295-eebf-4e13-b34b-5cbd138c6fc1","order_by":0,"name":"Indah Kurniawati","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYBACNgYGA2Ywg70BSBpYkKCFj+cASIsEURZBtMhJJIAoIrTwSTdv/FxQdliOTfL51Q0/CiQY+Nu7E/A7TOZYsfSMc4eN2aRzym72AB0mcebsBvxaJHIMpHnbDie2Seek3eABajGQyCWoxfg3UEt9m+SZtJt/iNRiBrIlgU2C/dhtIm1JK7PmOZdu2MaTw3ZbxkCCh6Bf5Gckb77NU2YtL99+/NnNN39s5Pjbe/FrgdoFIngMwCQRyuFa2B8QqXoUjIJRMApGGgAA9yg+yM4ZV+gAAAAASUVORK5CYII=","orcid":"","institution":"Dr. Cipto Mangunkusumo National Referral Hospital, University of Indonesia","correspondingAuthor":true,"prefix":"","firstName":"Indah","middleName":"","lastName":"Kurniawati","suffix":""},{"id":621431351,"identity":"ff9c40ef-7f4d-4052-b654-c7c3ab4d2be8","order_by":1,"name":"Yudianto Budi Saroyo","email":"","orcid":"","institution":"Dr. Cipto Mangunkusumo National Referral Hospital, University of Indonesia","correspondingAuthor":false,"prefix":"","firstName":"Yudianto","middleName":"Budi","lastName":"Saroyo","suffix":""},{"id":621431352,"identity":"dad4af74-609e-4af3-9180-6dfe977bf4ac","order_by":2,"name":"Muhammad Adya Firmansha Dilmy","email":"","orcid":"","institution":"Dr. Cipto Mangunkusumo National Referral Hospital, University of Indonesia","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Adya Firmansha","lastName":"Dilmy","suffix":""},{"id":621431353,"identity":"e721ca91-5ad8-441c-8c0b-1f8333449c82","order_by":3,"name":"Putri Maharani Tristanita Marsubrin","email":"","orcid":"","institution":"Dr. Cipto Mangunkusumo National Referral Hospital, University of Indonesia","correspondingAuthor":false,"prefix":"","firstName":"Putri","middleName":"Maharani Tristanita","lastName":"Marsubrin","suffix":""}],"badges":[],"createdAt":"2026-03-09 05:55:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9068763/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9068763/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107704959,"identity":"a6b4d932-268a-4967-a5d2-3a6df199903b","added_by":"auto","created_at":"2026-04-24 09:05:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":425519,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9068763/v1/fb1cffaa-d968-4093-a3ea-005ecd61a454.pdf"},{"id":107187682,"identity":"345e01f3-1943-40ff-a9ff-47576ee810b4","added_by":"auto","created_at":"2026-04-17 19:35:56","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1062948,"visible":true,"origin":"","legend":"","description":"","filename":"Informedconsent.docx","url":"https://assets-eu.researchsquare.com/files/rs-9068763/v1/03766cd4d9c19c79306fe4f4.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fetal Renal Artery Doppler Assessment in Early-Onset Fetal Growth Restriction and Its Association With Perinatal Outcomes: A Prospective Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eFetal growth restriction (FGR) is a major obstetric complication associated with increased perinatal morbidity and mortality worldwide. It affects approximately 5\u0026ndash;10% of pregnancies and represents one of the leading causes of stillbirth and neonatal complications. In addition to short-term neonatal morbidity, FGR has been associated with long-term risks such as cardiovascular disease, hypertension, and chronic kidney disease later in life.\u003c/p\u003e \u003cp\u003eThe most common underlying mechanism of FGR is placental insufficiency, which results in chronic fetal hypoxia and reduced nutrient supply. In response to hypoxia, the fetus undergoes circulatory redistribution, commonly known as the brain-sparing effect, in which blood flow is preferentially directed toward vital organs such as the brain and heart while perfusion to peripheral organs is reduced. One of the organs affected by this redistribution is the fetal kidney, which plays an important role in maintaining fetal fluid balance and renal development.\u003c/p\u003e \u003cp\u003eDoppler velocimetry is widely used to evaluate fetal hemodynamics in pregnancies complicated by FGR. Current clinical practice primarily focuses on Doppler assessment of the umbilical artery, middle cerebral artery, and ductus venosus to evaluate placental function and fetal adaptation to hypoxia. However, peripheral vessels such as the fetal renal artery may also provide important information regarding systemic vascular resistance and redistribution of fetal circulation.\u003c/p\u003e \u003cp\u003eDespite the potential physiological relevance of renal circulation in FGR, studies evaluating fetal renal artery Doppler parameters remain limited and their association with perinatal outcomes has not been clearly established. Therefore, this study aimed to evaluate fetal renal artery blood flow using Doppler ultrasound in pregnancies complicated by early-onset fetal growth restriction and to investigate its relationship with perinatal outcomes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eThis study was an observational analytic study with a prospective cohort design. The research was conducted at the Fetomaternal Clinic, operating theater, and Neonatal Intensive Care Unit (NICU) of Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia. Data collection was performed between October 2025 and February 2026.\u003c/p\u003e \u003cp\u003eThe study aimed to evaluate fetal renal artery Doppler indices in pregnancies complicated by early-onset fetal growth restriction (FGR) and to assess their association with perinatal outcomes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eThe study population consisted of pregnant women in the third trimester attending the Fetomaternal Clinic during the study period. Participants were divided into two groups, case group (pregnancies diagnosed with early-onset fetal growth restriction) and control group (pregnancies with normal fetal growth). All eligible women were recruited consecutively after providing written informed consent.\u003c/p\u003e\n\u003ch3\u003eEligibility criteria\u003c/h3\u003e\n\u003cp\u003eInclusion criteria\u003c/p\u003e \u003cp\u003eCase group\u0026rsquo;s inclusion criteria were singleton live fetus, gestational age between 28 and 40 weeks, and diagnosis of early-onset fetal growth restriction (\u0026lt;\u0026thinsp;32 weeks of gestation). For control group were singleton live fetus, gestational age between 28 and 40 weeks, and normal fetal growth according to gestational age.\u003c/p\u003e\n\u003ch3\u003eSample size\u003c/h3\u003e\n\u003cp\u003eBased on the calculation of sample size for correlation analysis, where α\u0026thinsp;=\u0026thinsp;0.05 (type I error), β\u0026thinsp;=\u0026thinsp;0.20 (power 80%), and the expected correlation coefficient was 0.5. The minimum required sample size was 24 participants per group. To account for potential dropouts, an additional 25% was added, resulting in 30 participants in each group. Therefore, a total of 60 participants were included in this study.\u003c/p\u003e\n\u003ch3\u003eSampling technique\u003c/h3\u003e\n\u003cp\u003eParticipants were recruited using consecutive sampling, in which all pregnant women meeting the inclusion criteria during the study period were included until the required sample size was achieved. Clinical and research data were recorded in a digital case report form and subsequently tabulated using Microsoft Excel 365 before statistical analysis.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDoppler ultrasound assessment\u003c/h2\u003e \u003cp\u003eFetal renal artery Doppler examinations were performed using obstetric ultrasonography equipment by a trained examiner. The examination was performed with the patient in a semi-recumbent position. The ultrasound probe was used to obtain a sagittal view of the fetal body, and the ultrasound beam was directed laterally to the vertebral column to obtain a coronal section of the fetal kidneys and descending aorta. Color Doppler was used to identify the renal artery entering the kidney. A pulsed Doppler sample gate measuring 2\u0026ndash;3 mm was placed at the center of the renal artery lumen. The Doppler parameters were optimized as follows high-pass filter: 30\u0026ndash;60 Hz, angle of insonation: as close as possible to 0\u0026deg; (not exceeding 30\u0026deg;), gain and wall filter adjusted appropriately and pulse repetition frequency adjusted for low-velocity flow\u003c/p\u003e \u003cp\u003eMeasurements were performed when the fetus was at rest and without fetal breathing movements. At least three consecutive waveforms were recorded, and each measurement was repeated twice. The mean value was used for analysis. Measurements were obtained from the renal artery with the best visualization (either right or left side). All Doppler examinations were performed by a single operator to minimize interobserver variability.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDoppler parameters\u003c/h3\u003e\n\u003cp\u003eThe following Doppler indices were recorded Pulsatility Index (PI) = (S-D)/TAMX. and Resistance Index (RI) = (S-D)/S, where S is peak systolic velocity (PSV), D is End-diastolic velocity (EDV), and TAMX is Time-averaged maximum velocity.\u003c/p\u003e\n\u003ch3\u003eUmbilical cord blood gas analysis\u003c/h3\u003e\n\u003cp\u003eUmbilical arterial blood samples were collected immediately after delivery. The umbilical cord was clamped at two points approximately 10\u0026ndash;20 cm from the neonate, and arterial blood was drawn using a heparinized syringe. Approximately 0.5\u0026ndash;1 mL of blood was obtained from the umbilical artery while avoiding air bubbles. Samples were analyzed within 15 minutes using a point-of-care blood gas analyzer (i-STAT system). The parameters analyzed included umbilical arterial pH and base excess (BE). Fetal acidemia was defined as umbilical arterial pH\u0026thinsp;\u0026lt;\u0026thinsp;7.00 and base excess\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;12 mmol/L\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eAll clinical and Doppler data were recorded in standardized case report forms and subsequently entered into Microsoft Excel for data management. Neonatal outcome data were obtained from hospital medical records.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 27.0. Categorical variables were presented as frequencies and percentages, whereas continuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median with interquartile range, depending on data distribution. Normality of the data was assessed using the Shapiro\u0026ndash;Wilk test. Comparisons between the early-onset FGR group and the control group were performed using the Mann\u0026ndash;Whitney U test for non-normally distributed data. The association between renal artery Doppler indices and perinatal outcomes (Apgar score, NICU admission, and fetal acidemia) was evaluated using Spearman correlation analysis. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (approval number: KET-1357/UN2.F1/ETIK.PPM.00.02/2025). Written informed consent was obtained from all participants prior to enrollment. Participant confidentiality was maintained throughout the study, and all data were anonymized before analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 60 pregnant women were included in this prospective observational study conducted at the Fetal Medicine Clinic of Cipto Mangunkusumo National Referral Hospital between October 2025 and February 2026. The study population consisted of two groups: 30 women with early-onset fetal growth restriction (FGR) and 30 women with normal singleton pregnancies serving as the control group.\u003c/p\u003e\n\u003cp\u003eAll recruited participants fulfilled the inclusion criteria and had complete maternal, Doppler, and neonatal outcome data available for analysis. No subjects were excluded due to missing neonatal outcome parameters.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaternal and neonatal characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe baseline characteristics of the study population are summarized in Table 1. In both groups, the majority of participants were multiparous (53.3%), while 46.7% were primiparous. The mean maternal age in the early-onset FGR group was 28.97 years (median 27.5 years), whereas in the control group the mean maternal age was slightly higher at 30.73 years (median 31.5 years). Pregnancies complicated by early-onset FGR were delivered at an earlier gestational age compared with normal pregnancies. The mean gestational age at delivery in the FGR group was 35.7 weeks (median 37.0 weeks), while in the control group it was 37.46 weeks (median 38.0 weeks). Neonatal birth weight differed substantially between groups. The mean birth weight in the early-onset FGR group was 1,925 g (median 2,120 g), whereas the control group had a significantly higher mean birth weight of 3,014 g (median 2,900 g). All neonates in the early-onset FGR group were categorized as small for gestational age (SGA), accounting for 100% of cases. In contrast, the majority of neonates in the control group were appropriate for gestational age (AGA) (96.7%), while one neonate (3.3%) was classified as large for gestational age (LGA).\u003c/p\u003e\n\u003cp\u003eMost neonates in both groups had satisfactory APGAR scores at 5 minutes. In the early-onset FGR group, 26 neonates (86.7%) had APGAR scores \u0026ge;7, while 4 neonates (13.3%) had APGAR scores \u0026lt;7. In the control group, almost all neonates had APGAR scores \u0026ge;7 (96.7%), and only one neonate (3.3%) had an APGAR score below 7. The mean APGAR score at 5 minutes was slightly lower in the FGR group (mean 8.3; median 9.0) compared with the control group (mean 9.1; median 9.0). Neonatal intensive care unit (NICU) admission was more common among neonates in the early-onset FGR group. Fourteen neonates (46.7%) required NICU admission, while 16 neonates (53.3%) did not require intensive care. In contrast, only two neonates (6.7%) in the control group required NICU admission, while the majority (93.3%) did not require intensive care. These findings demonstrate that pregnancies complicated by early-onset FGR were associated with a substantially higher need for neonatal intensive care.\u003c/p\u003e\n\u003cp\u003eTable 1. Maternal and Neonatal Characteristics\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img1776454376.png\" style=\"width: 552px;\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eNumerical data with normal distribution are presented as Mean \u0026plusmn; standard deviation\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003eNumerical data with abnormal distribution are presented as Median (Minimum-maximum)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDistribution of renal artery Doppler parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrior to comparative analysis, the distribution of the Doppler variables was assessed using the Shapiro\u0026ndash;Wilk normality test. The histogram of pulsatility index (PI) and resistance index (RI) demonstrated a unimodal distribution pattern without extreme skewness. However, statistical testing showed that several variables were not normally distributed. For the pulsatility index: early-onset FGR group: p = 0.041 (non-normal distribution) and control group: p = 0.095 (normal distribution). For the resistance index: early-onset FGR group: p = 0.002 (non-normal distribution) and control group: p = 0.066 (normal distribution). Because the Doppler parameters in the early-onset FGR group were not normally distributed, non-parametric statistical tests (Mann\u0026ndash;Whitney test) were used to compare Doppler parameters between groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComparison of renal artery Doppler parameters between groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe comparison of fetal renal artery Doppler parameters between the early-onset FGR group and the control group is shown in Table 2.\u003c/p\u003e\n\u003cp\u003eTable 2. Comparison of renal artery Doppler between groups\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"511\" height=\"67\" src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img1776454334.png\" alt=\"A black text on a white background Description automatically generated\" v:shapes=\"Picture_x0020_2\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eMann-Whitney test. Data are presented as Median (Minimum-Maximum), Statistical significance was defined as p-value \u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003ePulsatility Index (PI)\u003c/p\u003e\n\u003cp\u003eThe median pulsatility index differed slightly between the two groups, with a median difference of approximately 0.005. However, the Mann\u0026ndash;Whitney test showed that this difference was not statistically significant (p = 0.167). This finding indicates that the pulsatility index of the fetal renal artery did not differ significantly between pregnancies complicated by early-onset FGR and normal pregnancies.\u003c/p\u003e\n\u003cp\u003eResistance Index (RI)\u003c/p\u003e\n\u003cp\u003eIn contrast, the resistance index showed a statistically significant difference between groups. The median resistance index differed by approximately 0.003 between the early-onset FGR group and the control group. Statistical analysis using the Mann\u0026ndash;Whitney test demonstrated a significant difference between the two groups (p = 0.026). These results suggest that the resistance index of the fetal renal artery may better reflect alterations in peripheral vascular resistance associated with early-onset FGR compared with the pulsatility index.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation between renal artery Doppler parameters and perinatal outcomes in early-onset FGR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFurther analysis was performed to evaluate the relationship between fetal renal artery Doppler indices and perinatal outcomes among pregnancies complicated by early-onset FGR. The outcomes assessed included APGAR score at 5 minutes, NICU admission, umbilical artery pH, base excess (BE). Comparisons were conducted using the Mann\u0026ndash;Whitney test.\u003c/p\u003e\n\u003cp\u003eAPGAR score\u003c/p\u003e\n\u003cp\u003eThe analysis showed no statistically significant association between renal artery Doppler indices and APGAR score at 5 minutes. Both pulsatility index and resistance index values were similar between neonates with APGAR scores \u0026lt;7 and those with scores \u0026ge;7, indicating that renal artery Doppler parameters were not predictive of low APGAR score in this cohort.\u003c/p\u003e\n\u003cp\u003eNICU admission\u003c/p\u003e\n\u003cp\u003eSimilarly, no statistically significant association was found between renal artery Doppler parameters and NICU admission. Although neonates requiring NICU admission tended to have slightly different Doppler values, these differences did not reach statistical significance.\u003c/p\u003e\n\u003cp\u003eUmbilical artery pH\u003c/p\u003e\n\u003cp\u003eAnalysis of umbilical artery pH also demonstrated no significant correlation with renal artery pulsatility index or resistance index. Neonates with lower pH values did not exhibit significantly different renal artery Doppler indices compared with those with normal pH levels.\u003c/p\u003e\n\u003cp\u003eBase excess\u003c/p\u003e\n\u003cp\u003eNo statistically significant relationship was found between renal artery Doppler indices and base excess values. Although neonates with metabolic acidosis tended to show lower Doppler index values, the differences were not statistically significant.\u003c/p\u003e\n\u003cp\u003eOverall, this study demonstrated that fetal renal artery resistance index differed significantly between early-onset FGR and normal pregnancies, suggesting increased peripheral vascular resistance in FGR, Fetal renal artery pulsatility index did not show a significant difference between groups, Renal artery Doppler parameters were not significantly associated with short-term neonatal outcomes, including APGAR score, NICU admission, umbilical artery pH, or base excess. These findings suggest that while renal artery Doppler may reflect systemic hemodynamic adaptation in early-onset FGR, its ability to predict immediate perinatal outcomes may be limited.\u003c/p\u003e\n\u003cp\u003eTable 3. Association between Renal Artery Doppler and Neonatal Outcomes in Early Onset FGR\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"537\" src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img1776454335.png\" hspace=\"12\" v:shapes=\"Picture_x0020_3\" alt=\"image\"\u003e\u003c/p\u003e\n\u003cp\u003e*Mann-Whitney test. Statistical significance was defined as p-value \u0026lt;0.05\u003c/p\u003e\n\u003cp\u003eAdditional analyses (Umbilical artery / Middle cerebral artery comparison and ROC\u0026ndash;AUC)\u003c/p\u003e\n\u003cp\u003eTo contextualize fetal renal artery Doppler findings against established placental and cerebral Doppler parameters, we compared the discriminative performance of renal artery indices with umbilical artery Doppler measures in predicting neonatal acidemia.\u003c/p\u003e\n\u003cp\u003eReceiver operating characteristic (ROC) curve analysis (picture 1) showed that Doppler parameters reflecting placental resistance, particularly the umbilical artery systolic/diastolic ratio (UA S/D) and umbilical artery pulsatility index (UA PI), had better discriminative ability for predicting umbilical cord arterial pH than renal artery Doppler parameters.\u003c/p\u003e\n\u003cp\u003eThe area under the ROC curve (AUC) for UA S/D was 0.884 (p = 0.008), and the AUC for UA PI was 0.812 (p = 0.030), indicating good predictive performance for identifying neonates with abnormal cord pH (table 3). In contrast, fetal renal artery PI and RI did not demonstrate statistically significant discriminatory performance for neonatal outcomes such as acidemia, low 5-minute Apgar score, need for respiratory support, or NICU admission.\u003c/p\u003e\n\u003cp\u003eTabel 3. Area Under the Curve (AUC) of Doppler Parameters for Predicting Perinatal Outcomes\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"576\" height=\"135\" src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img177645433528.png\" v:shapes=\"Picture_x0020_4\" alt=\"image\"\u003e\u003c/p\u003e\n\u003cp\u003e*Nonparametric test; true area = 0.5. UA (umbilical artery), SD (S/D ratio), MCA (mid cerebral artery), RA (Renal artery)\u003c/p\u003e\n\u003cp\u003eThese findings support the concept that Doppler markers of placental impedance (umbilical artery indices) are more closely linked to acute acid\u0026ndash;base status at birth than peripheral organ Doppler indices, which may reflect earlier or more indirect adaptive responses\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eInterpretation of renal artery Doppler findings in early-onset FGR\u003c/p\u003e\n\u003cp\u003eThe present study demonstrated that the fetal renal artery resistance index (RI) was significantly higher in pregnancies complicated by early-onset fetal growth restriction (FGR) compared with normal pregnancies, whereas the pulsatility index (PI) did not show a statistically significant difference. This finding suggests that early-onset FGR is associated with increased peripheral vascular resistance, which may reflect adaptive hemodynamic changes in response to chronic fetal hypoxia.\u003c/p\u003e\n\u003cp\u003ePlacental insufficiency is the most common underlying mechanism of early-onset FGR and results in a chronic reduction in oxygen and nutrient delivery to the fetus. In response to hypoxemia, the fetus undergoes circulatory redistribution to preserve oxygen supply to vital organs such as the brain, myocardium, and adrenal glands. This adaptive response, commonly known as the brain-sparing effect, is characterized by vasodilation of cerebral vessels and vasoconstriction of peripheral circulation. As a consequence, blood flow to non-essential organs, including the kidneys, decreases. Reduced renal perfusion leads to increased vascular resistance within the renal artery, which can be detected by Doppler ultrasound as elevated resistance index values.\u003c/p\u003e\n\u003cp\u003eThe renal circulation plays an important role in fetal hemodynamic adaptation. Previous physiological studies have demonstrated that renal blood flow may decrease by up to 25\u0026ndash;50% in fetuses exposed to chronic hypoxia. Activation of the fetal sympathetic nervous system contributes to vasoconstriction of peripheral vessels, including the renal artery. This mechanism increases diastolic vascular resistance and consequently elevates Doppler indices such as RI. Therefore, the higher RI observed in the FGR group in the present study likely reflects the systemic peripheral vasoconstriction that occurs during fetal adaptation to placental insufficiency.\u003c/p\u003e\n\u003cp\u003eHowever, the clinical utility of renal artery Doppler remains controversial. Unlike umbilical artery or cerebroplacental Doppler indices, renal artery Doppler is not routinely included in current fetal surveillance guidelines. This is partly due to the limited number of studies evaluating its predictive value and the variability in measurement techniques across studies.\u003c/p\u003e\n\u003cp\u003eThe findings of the present study support the hypothesis that renal artery resistance increases in early-onset FGR as part of the fetal adaptive response to hypoxia. However, the absence of a significant association with neonatal outcomes suggests that renal artery Doppler may have limited value as an isolated predictor of perinatal morbidity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical implications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom a clinical perspective, the assessment of renal artery Doppler may provide additional insight into the systemic hemodynamic adaptation occurring in fetuses affected by placental insufficiency. Increased renal vascular resistance may reflect the redistribution of blood flow away from peripheral organs toward vital structures. Although this parameter may not independently predict neonatal outcomes, it may contribute to a more comprehensive understanding of fetal physiology in complicated pregnancies.\u003c/p\u003e\n\u003cp\u003eFuture research should explore the role of renal artery Doppler in combination with other established Doppler parameters, such as the umbilical artery, middle cerebral artery, and cerebroplacental ratio. A multimodal Doppler approach may improve the ability to identify fetuses at risk of deterioration and optimize the timing of delivery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom a clinical perspective, the assessment of renal artery Doppler may provide additional insight into the systemic hemodynamic adaptation occurring in fetuses affected by placental insufficiency. Increased renal vascular resistance may reflect the redistribution of blood flow away from peripheral organs toward vital structures. Although this parameter may not independently predict neonatal outcomes, it may contribute to a more comprehensive understanding of fetal physiology in complicated pregnancies.\u003c/p\u003e\n\u003cp\u003eFuture research should explore the role of renal artery Doppler in combination with other established Doppler parameters, such as the umbilical artery, middle cerebral artery, and cerebroplacental ratio. A multimodal Doppler approach may improve the ability to identify fetuses at risk of deterioration and optimize the timing of delivery.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFetal renal artery Doppler assessment provides insight into peripheral circulatory adaptation in pregnancies complicated by early-onset fetal growth restriction (FGR). In this study, the renal artery resistance index (RI) was significantly higher in early-onset FGR compared with normal pregnancies, indicating increased peripheral vascular resistance as part of the fetal response to chronic placental insufficiency. However, renal artery Doppler parameters were not significantly associated with short-term perinatal outcomes, including the 5-minute Apgar score, neonatal intensive care unit (NICU) admission, or fetal acidemia.\u003c/p\u003e\n\u003cp\u003eThese findings suggest that while renal artery Doppler reflects fetal hemodynamic adaptation, it has limited predictive value when used as a single parameter for adverse neonatal outcomes. Incorporating renal artery Doppler with established fetal Doppler indices may enhance the overall assessment of fetal circulatory status in early-onset FGR. Further research with larger cohorts is needed to clarify its clinical utility.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\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\"\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\"\u003eNICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeonatal Intensive Care Unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was approved by Ethics Committee Faculty of Medicine Universitas Indonesia (KET‑1357/UN2.F1/ETIK.PPM.00.02/2025). Written informed consent was obtained from all pregnant women prior to participation.\u003c/p\u003e\n\u003cp\u003eAuthor contribution\u003c/p\u003e\n\u003cp\u003eIK conceived the study, collected data, performed analysis, and wrote the manuscript.\u003c/p\u003e\n\u003cp\u003eConflict of interest\u003c/p\u003e\n\u003cp\u003eThe author declares no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNo external funding was received.\u003c/p\u003e\n\u003cp\u003eConsent for Publication\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eThe dataset generated and/or analyzed during the current study are not publicity available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLees CC, Stampalija T, Baschat AA, Da Silva Costa F, Ferrazzi E, Figueras F, et al. ISUOG Practice Guidelines: diagnosis and management of small-for‐gestational‐age fetus and fetal growth restriction. Ultrasound Obstet Gynecol. 2020;56(2):298\u0026ndash;312.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelamed N, Baschat A, Yinon Y, Athanasiadis A, Mecacci F, Figueras F, et al. FIGO initiative on fetal growth: Best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynecol Obstet. 2021;152(S1):3\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorris RK, Johnstone E, Lees C, Morton V, Smith G, the Royal College of Obstetricians and Gynaecologists. Investigation and Care of a Small-for‐Gestational‐ Age Fetus and a Growth Restricted Fetus. BJOG [Internet]. 2024 Aug [cited 2025 Jul 1];131(9). Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://obgyn.onlinelibrary.wiley.com/doi/\u003c/span\u003e\u003cspan address=\"https://obgyn.onlinelibrary.wiley.com/doi/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/1471- 0528.17814\u003c/span\u003e\u003cspan address=\"10.1111/1471- 0528.17814\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePerkumpulan Obstetri dan Ginekologi Indonesia HKFM (HKFM). Pedoman Nasional Pelayanan Kedokteran:Pengelolaan Kehamilan dengan Pertumbuhan Janin Terhambat. Jakarta: POGI; 2016.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArmengaud JB, Yzydorczyk C, Siddeek B, Peyter AC, Simeoni U. Intrauterine growth restriction: Clinical consequences on health and disease at adulthood. Reprod Toxicol. 2021;99:168\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure: Consensus definition of FGR. Ultrasound Obstet Gynecol. 2016;48(3):333\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma D, Shastri S, Sharma P. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects. Clin Med Insights Pediatr. 2016;10:CMPed.S40070.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNardozza LMM, Araujo J\u0026uacute;nior E, Rizzo G, Deter RL, editors. Fetal Growth Restriction: Current Evidence and Clinical Practice.Cham:Springer; 2019. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://link.springer.com/\u003c/span\u003e\u003cspan address=\"http://link.springer.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-030-00051-6\u003c/span\u003e\u003cspan address=\"10.1007/978-3-030-00051-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamphof HD, Posthuma S, Gordijn SJ, Ganzevoort W. Fetal Growth Restriction: Mechanisms, Epidemiology, and Management. Matern Fetal Med. 2022;4(3):186\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZafra R, Conway L, Solomon N. Prognostic Value of Doppler Ultrasound in Triplets Conceived by In Vitro Fertilization: A Case Report and Review of the Literature. J Investig Med High Impact Case Rep. 2019;7:2324709619864131.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBraga M, Moleiro ML, Guedes-Martins L. Clinical Significance of Ductus Venosus Waveform as Generated by Pressure- volume Changes in the Fetal Heart. Curr Cardiol Rev. 2019;15(3):167\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaulik D, Lees CC, editors. Doppler Ultrasound in Obstetrics and Gynecology [Internet]. 3rd ed. Cham: Springer; 2023. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/\u003c/span\u003e\u003cspan address=\"https://link.springer.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-031-06189-9\u003c/span\u003e\u003cspan address=\"10.1007/978-3-031-06189-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl Manshy KM, Elewa A, El Sherbeiny MF, El Sayed AM. Abnormal fetal Renal Artery Doppler. Benha J Appl Sci. 2022;7(8):91\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePravinchandra Ahya R, Unni J. Cross Sectional Study To Assess Perinatal Outcome Of Intrauterine Growth Restriction Babies Delivered In Jehangir Hospital, Pune, Maharashtra. Int J Life Sci Biotechnol Pharma Res. 2023;12(3):1889\u0026ndash;992.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Fetal growth restriction, Renal artery Doppler, Pulsatility index, Resistance index, Perinatal outcome","lastPublishedDoi":"10.21203/rs.3.rs-9068763/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9068763/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eFetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality. Chronic fetal hypoxia in FGR leads to redistribution of fetal circulation, prioritizing vital organs such as the brain while reducing perfusion to peripheral organs including the kidneys. Doppler assessment of the fetal renal artery may therefore reflect peripheral vascular resistance and potentially predict adverse perinatal outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eProspective observational cohort study conducted at Dr. Cipto Mangunkusumo National Hospital, Jakarta (October 2025\u0026ndash;February 2026). Doppler measurements of fetal renal artery pulsatility index (PI) and resistance index (RI) were obtained.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 60 participants were included (30 early‑onset FGR and 30 controls). Renal artery RI was significantly higher in early‑onset FGR (p\u0026thinsp;=\u0026thinsp;0.026). PI did not differ significantly between groups (p\u0026thinsp;=\u0026thinsp;0.167). No significant association was found between renal Doppler parameters and perinatal outcomes.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eRenal artery RI is increased in early‑onset FGR, suggesting increased peripheral vascular resistance. However, renal Doppler parameters were not significantly associated with perinatal outcomes.\u003c/p\u003e","manuscriptTitle":"Fetal Renal Artery Doppler Assessment in Early-Onset Fetal Growth Restriction and Its Association With Perinatal Outcomes: A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-17 19:35:53","doi":"10.21203/rs.3.rs-9068763/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-09T16:51:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"185455346052463103252929564733172885840","date":"2026-04-09T13:07:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-09T08:21:43+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-30T09:48:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-30T04:08:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-30T04:08:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2026-03-09T05:49:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9651a3f2-49a3-4c0f-ba77-7d9a79d3641d","owner":[],"postedDate":"April 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-17T19:35:53+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-17 19:35:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9068763","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9068763","identity":"rs-9068763","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}