Assessment of arterial pulsatility of cerebral perforating arteries using 7T high-resolution dual-VENC phase-contrast MRI.

PURPOSE: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T. METHODS: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated. RESULTS: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups. CONCLUSION: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD.

The association between discordant umbilical arterial resistance in growth-restricted fetuses and adverse outcomes.

BACKGROUND: Assessing the umbilical artery pulsatility index via Doppler measurements plays a crucial role in evaluating fetal growth impairment. OBJECTIVE: This study aimed to investigate perinatal outcomes associated with discordant pulsatility indices of umbilical arteries in fetuses with growth restriction. STUDY DESIGN: In this retrospective cohort study, all singleton pregnancies were included if their estimated fetal weight and/or abdominal circumference fell below the 10th percentile for gestational age (2017-2022). Eligible cases included singleton pregnancies with concurrent sampling of both umbilical arteries within 14 days of birth at the ultrasound evaluation closest to delivery. The exclusion criteria included births before 22 weeks of gestation, evidence of absent or reverse end-diastolic flow in either umbilical artery, and known fetal genetic or structural anomalies. The study compared cases with discordant umbilical artery pulsatility index values (defined as 1 umbilical artery pulsatility index at ≤95th percentile and the other umbilical artery pulsatility index at >95th percentile for gestational age) to pregnancies where both umbilical artery pulsatility indices had normal pulsatility index values and those with both umbilical arteries displaying abnormal pulsatility index values. The primary outcome assessed was the occurrence of composite adverse neonatal outcomes. Multivariable logistic regressions were performed, adjusting for relevant covariates. RESULTS: The study encompassed 1014 patients, including 194 patients (19.1%) with discordant umbilical artery pulsatility index values among those who had both umbilical arteries sampled close to delivery, 671 patients (66.2%) with both umbilical arteries having normal pulsatility index values, and 149 patients (14.7%) with both umbilical arteries exhibiting abnormal values. Pregnancies with discordant umbilical artery pulsatility index values displayed compromised sonographic parameters compared with those with both umbilical arteries showing normal pulsatility index values. Similarly, the number of abnormal umbilical artery pulsatility index values was associated with adverse perinatal outcomes in a dose-response manner. Cases with 1 abnormal (discordant) umbilical artery pulsatility index value showed favorable sonographic parameters and perinatal outcomes compared with cases with both abnormal umbilical artery pulsatility index values, and cases with both abnormal umbilical artery pulsatility index values showed worse sonographic parameters and perinatal outcomes compared with cases with discordant UA PI values. Multivariate analysis revealed that discordant umbilical artery pulsatility indices were significantly and independently associated with composite adverse perinatal outcomes, with an adjusted odds ratio of 1.75 (95% confidence interval, 1.24-2.47; P = .002). CONCLUSION: Evaluating the resistance indices of both umbilical arteries may provide useful data and assist in assessing adverse perinatal outcomes among fetuses with growth restriction.

Incidence, predictability, and outcomes of systemic venous congestion following a fluid challenge in initially fluid-tolerant preload-responders after cardiac surgery: a pilot trial.

BACKGROUND: Fluid administration has traditionally focused on preload responsiveness (PR). However, preventing fluid intolerance, particularly due to systemic venous congestion (VC), is equally important. This study evaluated the incidence and predictability of VC following a 7 ml/kg crystalloid infusion in fluid-tolerant preload-responders and its association with adverse outcomes. METHODS: This single-center, prospective, observational study (May 2023-July 2024) included 40 consecutive patients who were mechanically ventilated within 6 h of intensive care unit (ICU) admission after elective open-heart surgery and had acute circulatory failure. Patients were eligible if they were both fluid-tolerant and preload-responsive. PR was defined as a ≥ 12% increase in left-ventricular outflow tract velocity time integral (LVOT-VTI) 1 min after a passive leg raising (PLR) test. VC was defined by a portal vein pulsatility index (PVPI) ≥ 50%. Patients received a 7 ml/kg Ringer's Lactate infusion over 10 min. The primary outcome was the incidence of VC 2 min post-infusion (early-VC). Secondary outcomes included VC at 20 min, the incidence of acute kidney injury (AKI) and severe AKI at 7 days, and ICU length of stay (LOS). RESULTS: 45% of patients developed early-VC, with VC persisting in only 5% at 20 min. One-third of patients developed AKI, with 17.5% progressing to severe AKI. The median ICU LOS was 4 days. Patients with early-VC had significantly higher central venous pressure, lower mean perfusion pressure, worse baseline right ventricular function, and a higher incidence of severe AKI. While LVOT-VTI returned to baseline by 20 min in both groups, PVPI remained elevated in early-VC patients (p < 0.001). The LVOT-VTI versus PVPI regression line showed similar slopes (p = 0.755) but different intercepts (p < 0.001), indicating that, despite fluid tolerance and PR at baseline, early-VC patients had reduced right ventricular diastolic reserve (RVDR). Post-PLR PVPI predicted early-VC with an area under the curve of 0.998, using a threshold of 44.3% (p < 0.001). CONCLUSION: Post-PLR PVPI effectively predicts fluid-induced early-VC in fluid-tolerant preload-responders, identifying those with poor RVDR. Its use can guide fluid management in cardiac surgery patients, helping to prevent unnecessary fluid administration and associated complications. TRIAL REGISTRATION: NCT06440772. Registered 30 May 2024. Retrospectively registered.

Prediction by uterine artery Doppler screening of small-for-gestational-age neonates at 19-24 weeks' gestation.

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of screening performance of first-trimester competing-risks prediction model for small-for-gestational age in Asian population.

OBJECTIVE: To examine the external validity of the Fetal Medicine Foundation (FMF) competing-risks model for the prediction of small-for-gestational age (SGA) at 11-14 weeks' gestation in an Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 120 women with a singleton pregnancy undergoing routine assessment at 11-14 weeks' gestation. We applied the FMF competing-risks model for the first-trimester prediction of SGA, combining maternal characteristics and medical history with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) concentration. We calculated risks for different cut-offs of birth-weight percentile (< 10th , < 5th or < 3rd percentile) and gestational age at delivery (< 37 weeks (preterm SGA) or SGA at any gestational age). Predictive performance was examined in terms of discrimination and calibration. RESULTS: The predictive performance of the competing-risks model for SGA was similar to that reported in the original FMF study. Specifically, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA with birth weight < 10th percentile (SGA < 10th ) and preterm SGA with birth weight < 5th percentile (SGA < 5th ), with areas under the receiver-operating-characteristics curve (AUCs) of 0.765 (95% CI, 0.720-0.809) and 0.789 (95% CI, 0.736-0.841), respectively. Combining maternal factors with MAP and PlGF yielded the best model for predicting preterm SGA with birth weight < 3rd percentile (SGA < 3rd ) (AUC, 0.797 (95% CI, 0.744-0.850)). After excluding cases with pre-eclampsia, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA < 10th and preterm SGA < 5th , with AUCs of 0.743 (95% CI, 0.691-0.795) and 0.762 (95% CI, 0.700-0.824), respectively. However, the best model for predicting preterm SGA < 3rd without pre-eclampsia was the combination of maternal factors and PlGF (AUC, 0.786 (95% CI, 0.723-0.849)). The FMF competing-risks model including maternal factors, MAP, UtA-PI and PlGF achieved detection rates of 42.2%, 47.3% and 48.1%, at a fixed false-positive rate of 10%, for the prediction of preterm SGA < 10th , preterm SGA < 5th and preterm SGA < 3rd , respectively. The calibration of the model was satisfactory. CONCLUSION: The screening performance of the FMF first-trimester competing-risks model for SGA in a large, independent cohort of Asian women is comparable with that reported in the original FMF study in a mixed European population. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Rapid changes in cerebrovascular compliance during vasovagal syncope.

PURPOSE: The compensatory mechanisms supporting cerebral perfusion throughout head-up tilt (HUT) in patients with vasovagal syncope (VVS) remain unclear. We tested the hypothesis that increased cerebrovascular compliance (Ci) and decreased cerebrovascular resistance (CVR) support cerebral blood velocity (CBV) during pre-syncope in VVS. METHODS: Finger arterial blood pressure (ABP) and right middle cerebral artery blood velocity (CBV) were recorded in 15 individuals diagnosed with VVS (n = 11 female, mean age: 40 ± 16 years, mean body mass index: 24.9 ± 4.0 kg/m2) at supine rest and during HUT (80 degree angle). Individual ABP and CBV waveforms during VVS were input into a modified Windkessel model to calculate Ci and ohmic CVR. Gosling's pulsatility index (Pi; pulse amplitude/mean CBV) was calculated. RESULTS: Diastolic ABP, systolic ABP, mean ABP (72 ± 11 to 51 ± 12 mmHg), and CVR decreased progressively during presyncope (all P ≤ 0.04). As expected, systolic CBV was sustained (all P ≥ 0.29) while diastolic and mean CBV (51 ± 13 to 38 ± 13 mmHg) fell during presyncope (all P ≤ 0.04). Both Ci and Pi increased during presyncope (128 ± 97 and 60 ± 41%, respectively; all P ≤ 0.049) and were positively correlated (R2 = 0.79, P < 0.01). Increased Ci contributed to changes in mean CBV (P < 0.01) but decreased CVR did not (P = 0.28). CONCLUSIONS: These data provide evidence that Ci increases during presyncope in patients with VVS and is likely involved in the maintenance of systolic CBV during a fall in diastolic CBV. However, this regulation is not sufficient to preserve CBV in the presence of such extreme and progressive reductions in ABP.

Assessment of childhood intracranial pressure: a comparative study of transcranial Doppler ultrasound indices and findings at ventriculoperitoneal shunt.

PURPOSE: This study compares transcranial Doppler (TCD) Pulsatility Index (PI) and Resistivity Index (RI) with intra-operative CSF opening pressure measured by manometric technique during ventriculoperitoneal (V-P) shunt in children with hydrocephalus. METHODS: It was a prospective, hospital-based study performed among patients diagnosed with hydrocephalus. Patients had TCD ultrasonography before V-P shunt. The TCD sonography was repeated within 1 week post-op, and at 1 month post-op. The PI and RI were retrieved after insonating the middle cerebral artery. Ventricular CSF opening pressure was measured. Associations between TCD indices and CSF pressure were determined using the t-test and the Wilcoxon rank /Mann-Whitney tests where the normality test failed. A p-value of < 0.05 was considered significant for associations. RESULTS: Fifty-two patients were enrolled with a mean age of 9.9 ± 11.5 months. Of these, 41 (78.8%) were aged ≤ 12 months. The mean CSF opening pressure was 21.4 ± 9.0. When raised, ICP was defined as opening pressure > 15 cm of H2O, high PI (≥ 1.19), and high RI (> 0.8) diagnosed it with a sensitivity of 55% and 50%, respectively. The mean pre-operative PI (1.17 ± 0.56) reduced to 0.96 (Z = - 2.032, p = 0.042), while that of RI (0.66 ± 0.17) also decreased to 0.58 (t = 2.906, p = 0.044) after V-P shunt surgery. A strong positive correlation exists between a reduction in PI and RI after V-P shunt (r = 0.743, p = 0.014). CONCLUSION: Both PI and RI significantly decrease following V-P shunt, but a single reading has a poor sensitivity in predicting ICP.

Pulsatile Femoral Vein Doppler Pattern is a Parameter of Venous Congestion in ICU Patients.

OBJECTIVES: The aim of this study was to evaluate if the presence of a pulsatile femoral vein pattern is an indicator of venous congestion in the intensive care unit (ICU). DESIGN: Retrospective observational study. SETTING: Three medico-surgical university-affiliated ICUs. PARTICIPANTS: Adult patients who had an ultrasound evaluation at several time points during their ICU stay: at baseline (within 24 hours of admission to ICU), daily during their ICU stay, and within 24 hours before ICU discharge. INTERVENTIONS: At each time point, the hemodynamic, respiratory, and cardiac ultrasound parameters were recorded. The common femoral vein was studied with pulsed-wave Doppler at the level of the femoral trigonum, with high frequency (5-13 MHz) linear array vascular probe and venous vascular mode, in supine patients. MEASUREMENTS AND MAIN RESULTS: One hundred eight patients who underwent 400 ultrasound evaluations (3.7 ± 1 ultrasound evaluations per patient) during their ICU stay were included. Seventy-nine of 108 patients (73%) had a pulsatile femoral vein pattern at least at 1 time point. The multivariable mixed effects logistic regression model demonstrated an association among pulsatile femoral vein pattern, body mass index (OR: 0.91[95% CI 0.85-0.96], p = 0.002), inferior vena cava mean diameter (OR: 2.35 [95% CI 1.18-4.66], p = 0.014), portal vein pulsatility (OR: 2.3 [95% CI 1.2-4.4], p = 0.012), and congestive renal vein flow pattern (OR: 4.02 [95% CI 2.01-8.03], p < 0.001). The results were confirmed by principal component analysis. CONCLUSION: In the ICU, a pulsatile femoral vein pattern is associated with parameters of venous congestion, independently of the patient's volume status, and ventilatory treatment. These results suggest the femoral vein Doppler pulsatility as a parameter of congestion in ICU patients.

Assessment of Pulmonary Arterial Vascular Impedance in Fetuses With Tetralogy of Fallot.

OBJECTIVE: To evaluate the vascular impedance of the pulmonary arteries in fetuses with tetralogy of Fallot (TOF) by Doppler echocardiography. METHODS: A total of 42 fetuses with TOF (TOF group) and 84 gestational age-matched normal fetuses (control group) were prospectively collected from the Second Xiangya Hospital of Central South University from August 2022 to January 2023. The severity of TOF was classified into mild TOF (z score ≥-2), moderate TOF (-4 < z score < -2), or severe TOF (z score ≤-4) according to the z score value of the pulmonary annulus diameter. The pulsatility index (PI) of the main pulmonary artery (MPA), distal left pulmonary artery (DLPA), and distal right pulmonary artery (DRPA) were measured by pulsed-wave Doppler. The differences in clinical data and echocardiographic parameters between TOF group, control group, and TOF subgroups were compared. RESULTS: Compared with the control group, MPA-PI increased significantly, whereas DLPA-PI and DRPA-PI decreased in TOF group (all P < .001). There were no significant differences in MPA-PI and DRPA-PI among mild TOF, moderate TOF, and severe TOF (all P > .05). However, DLPA-PI decreased significantly in severe TOF compared with mild TOF (P < .05). CONCLUSION: Fetuses with TOF presented increased vascular impedance in the pulmonary trunk and decreased impedance in distal pulmonary artery branches. Further large and follow-up studies are needed to demonstrate the associations between those changed vascular impedances and the development of PA in patients with TOF.

Successful management of HeartMate 3 in a patient with arrhythmogenic right ventricular cardiomyopathy.

The management of right heart failure during durable left ventricular assist device (LVAD) support remains an unsolved issue so far. We had a 44-year-old male patient who was diagnosed with arrhythmogenic right ventricular cardiomyopathy and received HeartMate 3 LVAD (Abbott, USA) implantation as a bridge-to-transplant indication. The pump speed was adjusted as low as 4500 rpm to avoid the left ventricular narrowing and interventricular septal leftward shift. Riociguat was administered to decrease the afterload of the right ventricle and increase the preload of the left ventricle, in addition to the combination of neurohormonal blockers. Frequent low-flow alarm events eventually disappeared after amlodipine administration, and he was successfully returned to work. We here present a unique management in a patient with right heart failure due to arrhythmogenic right ventricular cardiomyopathy during HeartMate 3 LVAD support.

Incidence and first trimester risk factors of stillbirth in Indonesia.

OBJECTIVES: To determine the incidence and the risk factors of stillbirth from maternal biophysical, ultrasound, and biochemical markers at 11-13 weeks of gestation in the Indonesian population. METHODS: This was a retrospective cohort study of pregnant women for first-trimester preeclampsia screening at 11-13 weeks of gestation in some clinics and hospital in Jakarta. Maternal characteristics and history, mean arterial pressure (MAP) measurement, uterine artery pulsatility index (UtA-PI) ultrasound, maternal ophthalmic peak ratio (Oph-PR) Doppler, and placental growth factor (PlGF) serum were collected during the visit. Stillbirth was classified into placental dysfunction-related when it occurred with preeclampsia or birth weight <10th percentile and non-placental dysfunction-related. Bivariate and multivariate logistic regression analyses were employed to determine the risk factors associated with stillbirth. RESULTS: Of 1,643 eligible participants, 13 (0.79 %) stillbirth cases were reported. More than half of the stillbirths (7) were placental dysfunction-related. After adjusted with maternal age, body mass index (BMI), and parity status, chronic hypertension (aOR (adjusted odds ratio)) 24.41, 95 % CI {confidence interval} 5.93-100.43), previous pregnancy with preeclampsia (aOR 15.79, 95 % CI 4.42-56.41), MAP >101.85 (aOR 26.67, 95 % CI 8.26-86.06), UtA-PI >1.90 (aOR 10.68, 95 % CI 2.34-48.58, and PlGF <28.77 pg/mL (aOR 18.60, 95 % CI 5.59-61.92) were associated with stillbirth. CONCLUSIONS: The incidence of stillbirth in the population is comparable to studies conducted in developed countries. Most routine variables assessed at the 11-13 weeks combined screening for preeclampsia are associated with the risk of stillbirth.

Uterine arteries pulsatility index by Doppler ultrasound in the prediction of preeclampsia: an updated systematic review and meta-analysis.

BACKGROUND: Preeclampsia is a common pregnancy complication with serious potential risks for maternal and neonatal health. Early prediction of preeclampsia is crucial for timely prevention, surveillance, and treatment to improve maternal and neonatal outcomes. This systematic review aimed to summarize the available evidence on the prediction of preeclampsia based on Doppler ultrasound of uterine arteries at different gestational ages. METHODS: A systematic literature search and meta-analysis were conducted to evaluate the sensitivity and specificity of the pulsatility index of Doppler ultrasound of uterine arteries for predicting preeclampsia. The timing of ultrasound scans within and beyond 20 weeks of gestational age was compared to assess its effect on the sensitivity and specificity of the pulsatility index. RESULTS: This meta-analysis included 27 studies and 81,673 subjects (3309 preeclampsia patients and 78,364 controls). The pulsatility index had moderate sensitivity (0.586) and high specificity for predicting preeclampsia (0.879) (summary point: sensitivity 0.59; 1-specificity 0.12). Subgroup analysis revealed that ultrasound scans performed within 20 weeks of gestational age did not significantly affect the sensitivity and specificity for predicting preeclampsia. The summary receiver operator characteristic curve showed the pulsatility index's optimal range of sensitivity and specificity. CONCLUSIONS: The uterine arteries pulsatility index measured by Doppler ultrasound is useful and effective for predicting preeclampsia and should be implemented in the clinical practice. The timing of ultrasound scans at different gestational age ranges does not significantly affect the sensitivity and specificity.

The role of the cerebroplacental ratio in predicting pregnancy outcomes at 40-42 gestational weeks: a prospective observational trial.

PURPOSE: The cerebroplacental ratio is a sonographic tool used to predict poor pregnancy outcomes. Data are insufficient regarding its use in postdate pregnancy. We evaluated the cerebroplacental ratio's prediction of unfavorable pregnancy outcomes in women at 40-42 weeks gestation with normal amniotic fluid index. METHODS: This prospective observational study included 101 women with low-risk singleton pregnancy and gestational age > 40 weeks who delivered in a university affiliated hospital during 2020-2021. The middle cerebral artery pulsatility index, the umbilical artery pulsatility index, and the cerebroplacental ratio, which is their quotient, were compared between women with favorable and unfavorable pregnancy outcomes. The latter included: meconium-stained amniotic fluid, cesarean or vacuum-assisted delivery due to pathological cardiotocography (category 2 or 3), 5-min Apgar score < 7, umbilical cord pH < 7.1, neonatal intensive care unit admission, and neonatal death. RESULTS: Fetal Doppler, performed at a median gestational age of 40.3 (40.0-41.6), did not differ between 75 (74.3%) women with favorable obstetrical outcomes and 26 (25.7%) with unfavorable outcomes. In multivariate analysis, advanced maternal age and a history of a cesarean section were correlated with unfavorable outcomes, while Doppler indices were not found to be predictive. Among women at 41-42 weeks' gestation, for those with intrapartum fetal monitor category 2-3 vs. category 1, the mean umbilical artery pulsatility index was higher: 0.92 ± 0.34 vs. 0.71 ± 0.11 (p = 0.044). CONCLUSION: According to the study results, fetal Doppler indices, including the cerebroplacental ratio, are not predictive of unfavorable outcome in women with pregnancies exceeding 40 weeks. Larger prospective studies are needed.

Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method. DATA SOURCES: A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1- placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460). METHODS: Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, ß, θi, and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool. RESULTS: The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62-106.16 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 6.96; 95% confidence interval, 1.76-27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04-10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52-59.85 vs 7.09; 95% confidence interval, 3.74-13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67-33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41-14.35 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 14.94; 95% confidence interval, 9.42-23.70). CONCLUSION: Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery.

Feasibility and Clinical Value of Intraprocedural Doppler Ultrasonography Blood Flow Parameters During Peripheral Endovascular Procedures for Limb Salvage: A Pilot Study.

PURPOSE: To investigate whether Doppler ultrasound (DUS) blood flow parameters could serve as quantifiable functional endpoints of peripheral endovascular arterial procedures for chronic limb-threatening ischemia (CLTI), influencing wound healing. METHODS: This is a prospective single-center study investigating intraprocedural DUS parameters (pulsatility index [PI] and pedal acceleration time [PAT]) in quantifying immediate hemodynamic alterations in consecutive CLTI patients with wound, ischemia, and foot infection wound class ≥1 undergoing endovascular interventions. Primary endpoints were feasibility of preendovascular and postendovascular treatment measurements of PI/PAT, quantification of immediate PI/PAT modifications of the posterior and anterior foot circulation following revascularization, the correlation between PI and PAT, and 6-month complete wound healing. Secondary endpoints included the 6-month limb salvage (no major amputation) and complete and partial wound healing rates. RESULTS: A total of 28 patients (75.0% male) were enrolled, and 68 vessels were treated. The overall mean PAT values significantly decreased from 154.15±70.35 ms preprocedural to 107.21±49.6 ms postprocedural (p<0.01), and the mean PI values significantly increased from 0.93±0.99 to 1.92±1.96 (p<0.01). Postprocedural PAT at the anterior tibial (r2=0.804; p=0.346) and the posterior tibial arteries (r2=0.784; p=0.322) had a strong correlation and postprocedural PI at the anterior tibial (r2=0.704; p=0.301) and the posterior tibial arteries (r2=0.707; p=0.369) had a good correlation with 6-month complete wound healing. The 6-month complete and partial wound healing rates were 38.1% and 47.6%, respectively. Limb salvage was 96.4% and 92.4% at 6 and 12 months of follow-up, respectively. CONCLUSIONS: Pedal acceleration time and PI accurately detected immediate hemodynamic changes of foot perfusion following revascularization and could serve as prognostic factors of wound healing in patients with CLTI. CLINICAL IMPACT: Intraprocedural measurement of simple Doppler ultrasound blood flow parameters, Pulsatility Index (PI) and Pedal Acceleration Time (PAT), accurately detected immediate hemodynamic changes of foot perfusion following endovascular revascularization and could therefore serve as intraprocedural prognostic factors of wound healing in patients with chronic limb-threatening ischemia. This is the first time that PI has been proposed as a hemodynamic index of successful angioplasty outcome. The optimization of intraprocedural PAT and PI could be used to guide angioplasty and predict clinical success.

Placental biomarkers and fetoplacental Dopplers in combination reliably predict preterm birth in pregnancies complicated by fetal growth restriction.

OBJECTIVE: To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Dopplers - Umbilical Artery Pulsatility Index (UA PI) and Uterine Artery Pulsatility Index (UtA PI) in various combinations for the likelihood of preterm birth (PTB) in women with fetal growth restriction (FGR). METHODS: A prospective cohort study of pregnancies complicated by FGR. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA PI and UtA PI were measured at 4-weekly intervals from recruitment to delivery. Harrell's concordance statistic was used to evaluate various combinations of placental biomarkers and fetoplacental Dopplers to ascertain the ideal combination to predict PTB (<37 weeks). Multivariable Cox regression was used as time-varying covariates. RESULTS: There were 320 pregnancies in the study cohort - 179 (55.9%) were FGR and 141 (44.1%) were AGA. In the FGR cohort, both low PlGF levels and elevated sFlt-1/PlGF ratio significantly affected time to PTB. Low PlGF was a better predictor of PTB than either sFlt-1/PlGF ratio or combination of PlGF and sFlt-1/PlGF ratio (Harrell's C 0.81, 0.79, 0.75 respectively). Similarly, although both UA PI and UtA PI >95th centile for gestation significantly affected the time to PTB, in combination, they were better predictors than either measure alone (Harrell's C 0.82, 0.75, 0.76 respectively). The predictive utility was highest when PlGF <100ng/L, UA PI and UtA PI >95th centile was combined (Harrell's C 0.88) (HR 32.99 95% CI 10.74, 101.32). CONCLUSIONS: Low maternal PlGF levels (<100ng/L) and abnormal fetoplacental Dopplers (UA PI and UtA PI >95th centile) in combination have greatest predictive utility for PTB in pregnancies complicated with FGR and may help guide clinical management of these complex pregnancies. This article is protected by copyright. All rights reserved.

Reference ranges of uterine artery pulsatility index from first to third trimester based on serial Doppler measurements: longitudinal cohort study.

OBJECTIVE: To provide gestational-age (GA)-specific reference ranges for mean uterine artery (UtA) pulsatility index (PI) based on longitudinal data assessment throughout pregnancy. METHODS: This was a prospective longitudinal cohort study of singleton low-risk pregnancies with adequate health and nutritional status at the time of enrolment and without fetal anomaly, receiving prenatal care between January 2018 and July 2021 at the Maternal Fetal Medicine Unit of IRCCS San Raffaele Scientific Institute, Milan, Italy. Women were recruited at ≤ 12 + 6 weeks' gestation and underwent serial standardized ultrasound monitoring, including UtA-PI measurement, by experienced certified operators until delivery. Association of UtA-PI with GA was modeled with fractional polynomial regression. Equations for mean ± SD of the estimated curves were calculated, as well as GA-specific reference charts of centiles for UtA-PI from 10 + 0 to 39 + 0 gestational weeks. RESULTS: We included 476 healthy, low-risk pregnant women and a total of 2045 ultrasound scans (median, 4 (range, 3-9) per patient) were available for analysis. Mean UtA-PI was 1.84 ± 0.55, 1.07 ± 0.38 and 0.78 ± 0.23 in the first, second and third trimesters of pregnancy, respectively. Goodness-of-fit assessment revealed that second-degree smoothing was the most accurate fractional polynomial for describing the course of UtA-PI throughout gestation; therefore, it was modeled in a multilevel framework for the construction of UtA-PI curves. We observed a rapid and substantial decrease in mean UtA-PI before 16 weeks, with subsequent smoother decrement of the slope and more stable values from 20 until 39 weeks. The 3rd , 5th , 10th , 25th , 50th , 75th , 90th , 95th and 97th centiles according to GA for UtA-PI are provided, as well as equations to allow calculation of any value as a centile. CONCLUSIONS: UtA-PI shows a progressive non-linear decrease throughout pregnancy. The new reference ranges for GA-specific mean UtA-PI constructed using rigorous methodology may have a better performance compared with previous models for screening for placenta-associated diseases in the early stages of pregnancy and for evaluating the potential risk for pregnancy-induced hypertension and/or small-for-gestational age later in pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

External validation of Fetal Medicine Foundation competing-risks model for midgestation prediction of small-for-gestational-age neonates in Spanish population.

OBJECTIVE: To examine the external validity of the new Fetal Medicine Foundation (FMF) competing-risks model for prediction in midgestation of small-for-gestational-age (SGA) neonates. METHODS: This was a single-center prospective cohort study of 25 484 women with a singleton pregnancy undergoing routine ultrasound examination at 19 + 0 to 23 + 6 weeks' gestation. The FMF competing-risks model for the prediction of SGA combining maternal factors and midgestation estimated fetal weight by ultrasound scan (EFW) and uterine artery pulsatility index (UtA-PI) was used to calculate risks for different cut-offs of birth-weight percentile and gestational age at delivery. The predictive performance was evaluated in terms of discrimination and calibration. RESULTS: The validation cohort was significantly different in composition compared with the FMF cohort in which the model was developed. In the validation cohort, at a 10% false-positive rate (FPR), maternal factors, EFW and UtA-PI yielded detection rates of 69.6%, 38.7% and 31.7% for SGA < 10th percentile with delivery at < 32, < 37 and ≥ 37 weeks' gestation, respectively. The respective values for SGA < 3rd percentile were 75.7%, 48.2% and 38.1%. Detection rates in the validation cohort were similar to those reported in the FMF study for SGA with delivery at < 32 weeks but lower for SGA with delivery at < 37 and ≥ 37 weeks. Predictive performance in the validation cohort was similar to that reported in a subgroup of the FMF cohort consisting of nulliparous and Caucasian women. Detection rates in the validation cohort at a 15% FPR were 77.4%, 50.0% and 41.5% for SGA < 10th percentile with delivery at < 32, < 37 and ≥ 37 weeks, respectively, which were similar to the respective values reported in the FMF study at a 10% FPR. The model had satisfactory calibration. CONCLUSION: The new competing-risks model for midgestation prediction of SGA developed by the FMF performs well in a large independent Spanish population. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Added value of the pulmonary vein pulsatility index and its correlation to neonatal umbilical artery pH in fetal growth restrictions: a Vietnamese matched cohort study.

BACKGROUND: In clinical obstetrics, many guidelines recommended the use of Doppler fetal ductus venosus blood flow to monitor and to manage fetal growth restriction (FGR). The ductus venosus and the pulmonary venous flow pattern of fetuses are similar. Umbilical artery pH (UA pH) is essential in identifying adverse pregnancy outcomes, particularly in fetal growth restriction cases. Nevertheless, the literature indicates that the relationship between pulmonary vein pulsatility index (PVPI) and UA pH in FGR cases has not been well investigated. This study aimed to identify the alteration in PVPI in FGR cases and evaluate the correlation between PVPI and UA pH in FGR newborns. METHODS: This matched cohort study of singleton pregnancies from 28+ 0 to 40+ 0 weeks of gestation without congenital abnormalities included 135 cases of FGR (disease group) and 135 cases of normal growth (control group). The PVPI was measured at the proximal segment of the right or left pulmonary vein, approximately 5 mm from the left atrium wall. The umbilical artery pulsatility index (UAPI) was measured on the free umbilical cord. An elective cesarean section or labor induction are both options for ending the pregnancy, depending on the condition of the mother or fetus. Umbilical artery blood samples were collected within 5 min of delivery for UA pH measurement. SPSS version 20 and Medcalc version 20.1 were used for data analysis. RESULTS: FGR cases had a significantly higher mean fetal PVPI than the control group (1.16 ± 0.26 vs. 0.84 ± 0.16; p < 0.01), and PVPI and UAPI were positively correlated (r = 0.63; p < 0.001). PVPI and UA pH were negatively correlated in FGR patients, with r = -0.68; p < 0.001. The PVPI value on the 95th percentile had a prognostic value of UA pH < 7.20 with a sensitivity of 88.2%, specificity of 66.3%, positive predictive value of 46.9%, and negative predictive value of 94.3%. CONCLUSIONS: There was a statistically significant difference in PVPI values in FGR cases compared to the normal growth group, a positive correlation between PVPI and UAPI, and a negative correlation between PVPI and UA pH. PVPI might have a prognostic meaning in predicting UA pH at birth.

Association between transabdominal uterine artery Doppler and small-for-gestational-age: a systematic review and meta-analysis.

BACKGROUND: The association between uterine artery Doppler (UtA) measurements and small for gestational age (SGA) has not been quantitatively analyzed throughout the whole pregnancy. This systematic review and meta-analysis aims to comprehensively explore the association between UtA measurements and SGA in the first, second, and third trimesters. METHODS: Studies were searched from Pubmed, Embase, Cochrane Library, and Web of Science. Weighted mean difference (WMD), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were used as the effect size. Heterogeneity of all effect sizes was tested and quantified using I2 statistics. Sensitivity analysis was conducted for all outcomes, and publication bias was evaluated using Begg's test. RESULTS: A total of 41 studies were finally included in our meta-analysis. In the first trimester, mean PI was significantly higher in the SGA group than the non-SGA group (WMD: 0.31, 95%CI: 0.19-0.44). In the second trimester, odds of notch presence (OR: 2.54, 95%CI: 2.10-3.08), mean PI (WMD: 0.21, 95%CI: 0.12-0.30), and mean RI (WMD: 0.05, 95%CI: 0.05-0.06) were higher in the SGA group. Also, abnormal UtA measurements were associated with the increased odds of SGA (all P < 0.05). In the third trimester, PI z-score (WMD: 0.62, 95%CI: 0.33-0.91) and PI MoM (WMD: 0.08, 95%CI: 0.06-0.09) showed a significant increase in the SGA group. The odds of SGA were higher in the women with mean PI > 95% (OR: 6.03, 95%CI: 3.24-11.24). CONCLUSIONS: Abnormal UtA measurements were associated with high odds of SGA, suggesting that UtA might be an adjunctive screening method for SGA in the whole pregnancy.