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Objective: To evaluate amniotic fluid volume with Doppler parameters and its association with composite adverse perinatal outcomes (CAPOs) in fetal growth restriction (FGR). Materials and Methods: This study was conducted prospectively in a tertiary referral center between 2023 and 2024 on pregnant women diagnosed with early‐ and late‐onset FGR. Fetal ultrasonographic measurements, including deepest vertical pocket (DVP) for amniotic fluid, and Doppler parameters including uterine artery (UtA) systolic/diastolic (S/D) and pulsatility index (PI), middle cerebral artery (MCA) S/D and PI, and umbilical artery (UA) S/D and PI, were conducted following fetal biometry. The cerebroplacental ratio (CPR), cerebral ratio, cerebro‐placental‐uterine ratio (CPUR), and amniotic‐umbilical‐to‐cerebral ratio (AUCR) were all calculated. Pregnant women diagnosed with FGR were planned to give birth after 37 weeks' gestation, unless a pregnancy complication requiring earlier delivery occurred. We assessed perinatal outcomes subsequent to delivery, with CAPOs defined as the presence of at least one adverse outcome: 5th minute APGAR score <7, respiratory distress syndrome (RDS), umbilical cord blood pH <7.2, and neonatal intensive care unit (NICU) admission. Results: The study included 132 participants, divided into early‐ (n = 32) and late‐onset FGR (n = 100) groups. AUCR was significantly lower in fetuses with late‐onset FGR who experienced CAPOs. Multivariate analysis showed gestational age at birth and birth weight were significant predictors of CAPOs in early‐onset FGR, while gestational age, birth weight, and AUCR were significant predictors in late‐onset FGR. CPR, UCR, and CPUR did not show significance in predicting CAPOs in both early‐ and late‐onset FGR on multivariate analysis. Conclusions: AUCR is a potential reliable marker for predicting adverse perinatal outcomes in late‐onset FGR. [ABSTRACT FROM AUTHOR]

Objective: To assess the association of the umbilicocerebral ratio (UCR) with adverse perinatal outcome in late preterm small‐for‐gestational age (SGA) fetuses and to investigate the effect on perinatal outcomes of immediate delivery. Design: Multicentre cohort study with nested randomised controlled trial (RCT). Setting: Nineteen secondary and tertiary care centres. Population: Singleton SGA pregnancies (estimated fetal weight [EFW] or fetal abdominal circumference [FAC] <10th centile) from 32 to 36+6 weeks. Methods: Women were classified: (1) RCT‐eligible: abnormal UCR twice consecutive and EFW below the 3rd centile at/or below 35 weeks or below the 10th centile at 36 weeks; (2) abnormal UCR once or intermittent; (3) never abnormal UCR. Consenting RCT‐eligible patients were randomised for immediate delivery from 34 weeks or expectant management until 37 weeks. Main outcome measures: A composite adverse perinatal outcome (CAPO), defined as perinatal death, birth asphyxia or major neonatal morbidity. Results: The cohort consisted of 690 women. The study was halted prematurely for low RCT‐inclusion rates (n = 40). In the RCT‐eligible group, gestational age at delivery, birthweight and birthweight multiple of the median (MoM) (0.66, 95% confidence interval [CI] 0.59–0.72) were significantly lower and the CAPO (n = 50, 44%, p < 0.05) was more frequent. Among patients randomised for immediate delivery there was a near‐significant lower birthweight (p = 0.05) and higher CAPO (p = 0.07). EFW MoM, pre‐eclampsia, gestational hypertension and Doppler classification were independently associated with the CAPO (area under the curve 0.71, 95% CI 0.67–0.76). Conclusions: Perinatal risk was effectively identified by low EFW MoM and UCR. Early delivery of SGA fetuses with an abnormal UCR at 34–36 weeks should only be performed in the context of clinical trials. [ABSTRACT FROM AUTHOR]

Background: Purpose Aim of our study was to compare the prognostic value of the Umbilicalto-Cerebral ratio (UCR) directly to the Cerebroplacental ratio (CPR) in the prediction of poor perinatal outcomes in pregnancies complicated by Fetal Growth Restriction (FGR). Methods: A retrospective study was carried out on pregnant women with either a small-forgestational-age (SGA) fetus or that were diagnosed with FGR. Doppler measurements of the two subgroups were assessed, and the correlation between CPR, UCR, and relevant outcome parameters was evaluated by performing linear regression analysis, binary logistic analysis, and receiver operator characteristic (ROC) curves. Outcomes of interest were mode of delivery, acidosis, preterm delivery, gestational age at birth as well as birthweight and centiles. Results: Boxplots and Scatterplots illustrated the different distribution of CPR and UCR leading to deviant correlational relationships with adverse outcome parameters. In almost all parameters examined, UCR showed a higher independent association with preterm delivery (OR: 5.85, CI 2.23-15.34), APGAR score<7 (OR: 3.52; CI 1.58-7.85) as well as weight under the 10th centile (OR: 2.04; CI 0.97-4.28) in binary logistic regression compared to CPR, which was only associated with preterm delivery (OR: 0.38; CI 0.22-0.66) and APGAR score<7 (OR: 0.27; CI 0.06-1.13). When combined with different ultrasound parameters to differentiate between SGA and FGR during pregnancy, odds ratios for UCR were highly significant compared to odds ratios for CPR (OR: 0.065, 0.168-0.901; p=0.027; OR: 0.810, 0.369-1.781; p=0.601). ROC curves plotted for CPR and UCR showed almost identical moderate prediction performance. Conclusion: These findings indicate that the UCR should be prospectively examined as a prognostic tool while keeping the statistical characteristics and challenges of reversing the ratio in mind. [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of this study was to investigate the prediction of adverse perinatal outcomes using the cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in different cohorts of singleton pregnancies. Materials and Methods: In this retrospective cohort study, we established our own Multiple of Median (MoM) for CPR and UCR. The predictive value for both ratios was studied in the following outcome parameters: emergency cesarean delivery, operative intervention (OI), OI due to fetal distress, 5-min Apgar < 7, admission to neonatal intensive care unit, and composite adverse perinatal outcome. The performance of the ratios was assessed in the following cohorts: total cohort (delivery ≥ 37 + 0 weeks gestation, all birth weight centiles), low-risk cohort (delivery ≥ 37 + 0 weeks gestation, birth weight ≥ 10. centile), prolonged pregnancy cohort (delivery ≥ 41 + 0 weeks gestation, birth weight ≥ 10. centile) and small-for-gestational-age fetuses (delivery ≥ 37 + 0 weeks gestation, birth weight < 10. centile). The underlying reference values for MoM were estimated using quantile regression depending on gestational age. Prediction performance was evaluated using logistic regression models assessing the corresponding Brier score, combining discriminatory power and calibration. Results: Overall, 3326 cases were included. Across all cohorts, in the case of a significant association between a studied outcome parameter and CPR, there was an association with UCR, respectively. The Brier score showed only minimal differences for both ratios. Conclusions: Our study provides further evidence regarding predictive values of CPR and UCR. The results of our study suggest that reversal of CPR to UCR does not improve the prediction of adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

Introduction: An abnormal third trimester cerebroplacental ratio has been previously associated with adverse perinatal outcome. The less studied inverse of the cerebroplacental ratio, the umbilicocerebral ratio, has been proposed as a better predictor of adverse perinatal outcome. However, little is known about the implication of either an abnormal cerebroplacental ratio or umbilicocerebral ratio in the second trimester. The objective of this study was to evaluate the relationship between an abnormal second trimester cerebroplacental ratio and adverse perinatal outcome and provide comparison to an abnormal second trimester umbilicocerebral ratio. Materials and methods: This retrospective cohort study in a single tertiary referral center utilized data from all non-anomalous singleton pregnancies that underwent Doppler assessment of the cerebroplacental ratio between 20 and 28 weeks gestation. The study period was 1 January 2015 to 31 July 2018. Abnormal cerebroplacental ratio was defined as less than the 5th percentile for gestational age. If patients had more than one ultrasound during the study period (i.e. for serial assessment of fetal growth), the lowest value of the cerebroplacental ratio was recorded. The primary outcome was a composite of clinically relevant adverse perinatal outcomes including preterm delivery, small for gestational age, and neonatal intensive care unit admission. Secondary outcomes included urgent delivery for fetal distress (operative vaginal delivery or cesarean section) and hypertensive disorders of pregnancy. An abnormal umbilicocerebral ratio was defined as greater than 95th percentile for gestational age. Areas under the curve were calculated and compared for cerebroplacental ratio and umbilicocerebral ratio. Results: 2326 pregnancies met inclusion criteria. Of these, 91 (3.9%) had an abnormal second trimester cerebroplacental ratio. Fetuses with an abnormal second trimester cerebroplacental ratio had a 2.3-fold (95% CI 1.5–3.6, p < .05) increased risk of adverse perinatal outcome after adjusting for potential confounders such as chronic hypertension, pregestational diabetes, and smoking during pregnancy. Significantly increased risks of preterm delivery (OR 2.0, 95% CI 1.1–38, p < .05) and neonatal intensive care unit admission (OR 2.1, 95% CI 1.2–3.6, p < .05) were also seen in a subgroup analysis of abnormal cerebroplacental ratio in appropriate for gestational age infants. 132 (5.7%) fetuses had an abnormal second trimester umbilicocerebral ratio, and these fetuses had a 2.0-fold (95% CI 1.4–3.0, p < .05) increased risk of adverse perinatal outcome. The area under the curve for CPR and UCR for prediction of the primary outcome was 0.6 for both (95% CI 0.57–0.61 and 0.57–0.62, respectively, both p < .05). Conclusion: An abnormal second trimester cerebroplacental ratio or umbilicocerebral ratio is associated with adverse perinatal outcome. However, the predictive ability of either ratio remains suboptimal. [ABSTRACT FROM AUTHOR]

Objective The cerebroplacental ratio (CPR) has shown utility as a surrogate marker for fetal growth restriction and can be used to stratify the risk for adverse perinatal outcomes in affected pregnancies. However, recent studies suggest that its inverse, the umbilico-cerebral ratio (UCR), may be a better predictor of such outcomes. The aim of this study was to compare the prognostic accuracy of CPR to that of UCR Doppler in predicting short-term adverse perinatal outcomes in growth-restricted fetuses. Methods We conducted a secondary analysis using data from a prospective study on women referred for fetal growth ultrasounds between 26 and 36 weeks of gestation and with an EFW < 10th percentile by Hadlock standard. The CPR and UCR were converted into Z-scores adjusted for gestational age at ultrasound. Abnormal CPR was defined as Z-score below the 10th percentile for the gestational age and abnormal UCR as Z-score above the 90th percentile. We calculated sensitivity and specificity of the two Doppler parameters for predicting composite adverse perinatal outcome (APO) defined as the presence of any one of the following: umbilical cord arterial pH <7.10, Apgars at 5 min <7, NICU admission,grade III/IV intraventricular hemorrhage (IVH), neonatal seizure and death. Logistic regression analysis was performed, ROC curves plotted and the area under the ROC curve (AUC) were compared between CPR and UCR. Results Over the study period, there were 197 women meeting inclusion criteria, of which 27 (13.7%) had a composite adverse neonatal outcome. The sensitivity using CPR Z-score for predicting the composite APO was higher thanwas similar to using UCR Z-score (39.3% compared with 37%) for a similar specificity (94.7 versus 94.1), respectively. However, the positive predictive value (PPV) was higher for CPR (55% vs UCR 50%) and the negative predictive values (NPV) were similar. For a fixed false positive rate of 10%, the detection rates for adverse neonatal outcomes were 40% using either CPR or UCR. The AUC for CPR and UCR were 0.70 and 0.68, respectively. Conclusion This study did not find any advantage in utilizing the UCR over the CPR. [ABSTRACT FROM AUTHOR]

Objective: There is a lack of evidence on whether to favor cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) when assessing pregnancies at risk of fetal growth restriction. The Recent evidences highlight a significant heterogeneity in the methodology of previously published studies reporting reference ranges for Doppler indices, which may affect the clinical applicability of these charts. The aim of this study was to develop charts of UCR based upon a recently proposed standardized methodology and using quantile regression.Methods: This was a secondary analysis of a prospective cross-sectional study including low-risk singleton pregnancies between 24 and 40 weeks of gestation undergoing Doppler recordings. The UCR centile values were established by quantile regression at different gestational age intervals. Quantile regression analysis was used to build the UCR chart.Result: 2516 low- risk singleton pregnancies were included in the analysis. UCR decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age are provided, as well as equations to allow calculation of any other percentile.Conclusions: We have established gestational age-specific normative centiles reference limits for UCR. [ABSTRACT FROM AUTHOR]

Background: The clinical inability to correctly identify late fetal growth restriction (FGR) within a group of fetuses who are identified as small for gestational age (SGA) is an everyday problem for all obstetrician-gynecologists. This leads to substantial overtreatment of healthy small fetuses but also inadequate detection of the growth-restricted fetuses that may benefit from timely delivery. Redistribution of the fetal circulation, signaled by an abnormal ratio of the Doppler velocity flow profiles of the umbilical artery and the middle cerebral artery, more specifically an increased umbilicocerebral ratio (UCR) (or its inverse: a decreased cerebroplacental ratio (CPR)), is an adaptation to chronic hypoxemia and nutritional scarcity with long-term consequences in survivors. The relevance of an abnormal UCR has been signaled extensively, and there is a general consensus that it is a signal of FGR, independent of size, with a strong association with poor outcomes. Yet, in the current literature, no comparisons of a monitoring-delivery strategy based on unfavorable UCR have been published. The objective of the Doppler Ratio In fetal Growth restriction Intervention Trial At (near) Term (DRIGITAT) is to evaluate if the timing of the delivery based on an abnormal UCR in late preterm fetuses identified as SGA improves neurodevelopmental outcomes at 2 years of age.Methods: The DRIGITAT study is a national multicenter cohort study of women with singleton pregnancies between 32 and 37 weeks of gestation identified as SGA, with a nested randomized controlled trial (RCT) in case of an abnormal UCR (> 0.8). Recruiting centers are in The Netherlands. In the nested RCT, women are randomized to either immediate induction of labor or expectant management from 34 weeks in case of severely abnormal size (EFW or FAC < p3) and from 36 weeks in case of mildly abnormal size (EFW or FAC p3-p10). The primary outcome measure is the 7-point average difference in the composite cognitive score (CCS) and composite motor score (CMS) on the Bayley-3 at 2 years. Secondary outcome measures include a composite outcome of neonatal morbidity, perinatal mortality, mode of delivery, maternal quality of life, costs, and predictive value of serum biomarkers. Analyses will be by intention to treat. The required sample size is determined for the nested RCT as 185 patients.Discussion: This study will provide insight into the diagnostic efficacy of UCR measurement in the evaluation of SGA fetuses in order to differentiate the healthy SGA fetus from the growth-restricted fetus and to determine if a fetus with abnormal UCR benefits from early delivery.Trial Registration: Healthcare Evaluation Netherlands NTR6663 . Registered on 14 August 2017. [ABSTRACT FROM AUTHOR]

Purpose: Aim of our study was to compare the prognostic value of the Umbilical-to-Cerebral ratio (UCR) directly to the Cerebroplacental ratio (CPR) in the prediction of poor perinatal outcomes in pregnancies complicated by Fetal Growth Restriction (FGR). Methods: A retrospective study was carried out on pregnant women with either a small-for-gestational age (SGA) fetus or that were diagnosed with FGR. Doppler measurements of the two subgroups were assessed and the correlation between CPR, UCR and relevant outcome parameters was evaluated by performing linear regression analysis, binary logistic analysis and receiver operator characteristic (ROC) curves. Outcomes of interest were mode of delivery, acidosis, preterm delivery, gestational age at birth as well as birthweight and centiles. Results: Boxplots and Scatterplots illustrated the different distribution of CPR and UCR leading to deviant correlational relationships with adverse outcome parameters. In almost all parameters examined, UCR showed a higher independent association with preterm delivery (OR: 5.85, CI 2.23–15.34), APGAR score < 7 (OR: 3.52; CI 1.58–7.85) as well as weight under 10th centile (OR: 2.04; CI 0.97–4.28) in binary logistic regression compared to CPR which was only associated with preterm delivery (OR: 0.38; CI 0.22–0.66) and APGAR score < 7 (OR: 0.27; CI 0.06–1.13). When combined with different ultrasound parameters in order to differentiate between SGA and FGR during pregnancy, odds ratios for UCR were highly significant compared to odds ratios for CPR (OR: 0.065, 0.168–0.901; p = 0.027; OR: 0.810, 0.369–1.781; p = 0.601). ROC curves plotted for CPR and UCR showed almost identical moderate prediction performance. Conclusion: Since UCR is a better discriminator of Doppler values in abnormal range it presents a viable option to Doppler parameters and ratios that are used in clinical practice. UCR and CPR showed equal prognostic accuracy conserning sensitivity and specificity for adverse perinatal outcome, while adding UA PI and GA_scan increased prognostic accuracy regarding negative outcomes. [ABSTRACT FROM AUTHOR]

Objectives: First, to compare published Doppler reference charts of the ratios of flow in the fetal middle cerebral and umbilical arteries (i.e. the cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR)). Second, to assess the association of thresholds of CPR and UCR based on these charts with short-term composite adverse perinatal outcome in a cohort of pregnancies considered to be at risk of late preterm fetal growth restriction.Methods: Studies presenting reference charts for CPR or UCR were searched for in PubMed. Formulae for plotting the median and the 10th percentile (for CPR) or the 90th percentile (for UCR) against gestational age were extracted from the publication or calculated from the published tables. Data from a prospective European multicenter observational cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks' gestation, in which fetal arterial Doppler measurements were collected longitudinally, were used to compare the different charts. Specifically, the association of UCR and CPR thresholds (CPR < 10th percentile or UCR ≥ 90th percentile and multiples of the median (MoM) values) with composite adverse perinatal outcome was analyzed. The association was also compared between chart-based thresholds and absolute thresholds. Composite adverse perinatal outcome comprised both abnormal condition at birth and major neonatal morbidity.Results: Ten studies presenting reference charts for CPR or UCR were retrieved. There were large differences between the charts in the 10th and 90th percentile values of CPR and UCR, respectively, while median values were more similar. In the gestational-age range of 28-36 weeks, there was no relationship between UCR or CPR and gestational age. From the prospective observational study, 856 pregnancies at risk of late-onset preterm fetal growth restriction were included in the analysis. The association of abnormal UCR or CPR with composite adverse perinatal outcome was similar for percentile thresholds or MoM values, as calculated from the charts, and for absolute thresholds, both on univariable analysis and after adjustment for gestational age at measurement, estimated fetal weight MoM and pre-eclampsia. The adjusted odds ratio for composite adverse perinatal outcome was 3.3 (95% CI, 1.7-6.4) for an absolute UCR threshold of ≥ 0.9 or an absolute CPR threshold of < 1.11 (corresponding to ≥ 1.75 MoM), and 1.6 (95% CI, 0.9-2.9) for an absolute UCR threshold of ≥ 0.7 to < 0.9 or an absolute CPR threshold of ≥ 1.11 to < 1.43 (corresponding to ≥ 1.25 to < 1.75 MoM).Conclusions: In the gestational-age range of 32 to 36 weeks, adjustment of CPR or UCR for gestational age is not necessary when assessing the risk of adverse outcome in pregnancies at risk of fetal growth restriction. The adoption of absolute CPR or UCR thresholds, independent of reference charts, is feasible and makes clinical assessment simpler than if using percentiles or other gestational-age normalized units. The high variability in percentile threshold values among the commonly used UCR and CPR reference charts hinders reliable diagnosis and clinical management of late preterm fetal growth restriction. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >−11 mEq/mL, or neonatal intensive care unit admission). Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512–0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507–0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR. [ABSTRACT FROM AUTHOR]

Objectives: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction.Methods: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored.Results: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association.Conclusion: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: Observational studies have shown that low cerebroplacental ratio (CPR) values predict an increased risk of adverse perinatal outcome. The inverse ratio, i.e. the umbilicocerebral ratio (UCR), has been suggested to be a better predictor as it rises with increasing degree of fetal compromise. However, longitudinal reference ranges for UCR have not been established, and whether gestational-age-dependent changes in CPR or UCR differ between male and female fetuses has not been studied. Thus, the aims of this study were to investigate sex-specific, gestational-age-associated serial changes in CPR and UCR during the second half of pregnancy and to establish longitudinal reference ranges.Methods: This was a secondary analysis of prospectively collected data from a dual-center longitudinal observational cohort study of low-risk singleton pregnancies. Doppler blood-flow velocity waveforms were obtained serially from the umbilical artery (UA) and fetal middle cerebral artery (MCA) from 19-41 weeks' gestation, and pulsatility indices (PIs) were determined. CPR and UCR were calculated as the ratios MCA-PI/UA-PI and UA-PI/MCA-PI, respectively. The course and outcome of pregnancies were recorded, and the sex of the fetus was determined after delivery. Reference intervals for CPR and UCR were constructed using multilevel modeling, and gestational-age-specific Z-scores in male and female fetuses were compared.Results: Of a total of 299 pregnancies enrolled, 284 (148 male and 136 female fetuses) were included in the final analysis, and 979 paired measurements of UA-PI and MCA-PI were used to construct sex-specific longitudinal reference intervals. The relationship of both CPR and UCR with gestational age was U-shaped, but in opposite directions. There was a small but significant difference in Z-scores of CPR and UCR between male and female fetuses throughout the second half of pregnancy (P = 0.007).Conclusions: We have established longitudinal reference ranges for CPR and UCR suitable for serial monitoring, with the possibility of refining assessment by using fetal sex-specific ranges and conditioning by a previous measurement. The clinical significance of such refinements needs further evaluation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]