Umbilical Vein Flow Research Articles

The role of umbilical vein flow rate and foetal growth velocity in predicting iatrogenic preterm birth and adverse perinatal outcomes in a population of small foetuses

The role of umbilical vein flow rate and foetal growth velocity in predicting iatrogenic preterm birth and adverse perinatal outcomes in a population of small foetuses

Dihydromyricetin suppresses endothelial NLRP3 inflammasome activation and attenuates atherogenesis by promoting mitophagy

BackgroundNOD-like receptor protein 3 (NLRP3) inflammasome activation is indispensable for atherogenesis. Mitophagy has emerged as a potential strategy to counteract NLRP3 inflammasome activation triggered by impaired mitochondria. Our previous research has indicated that dihydromyricetin, a natural flavonoid, can mitigate NLRP3-mediated endothelial inflammation, suggesting its potential to treat atherosclerosis. However, the precise underlying mechanisms remain elusive. This study sought to investigate whether dihydromyricetin modulates endothelial mitophagy and inhibits NLRP3 inflammasome activation to alleviate atherogenesis, along with the specific mechanisms involved.MethodsApolipoprotein E-deficient mice on a high-fat diet were administered daily oral gavages of dihydromyricetin for 14 weeks. Blood samples were procured to determine the serum lipid profiles and quantify proinflammatory cytokine concentrations. Aortas were harvested to evaluate atherosclerotic plaque formation and NLRP3 inflammasome activation. Concurrently, in human umbilical vein endothelial cells, Western blotting, flow cytometry, and quantitative real-time PCR were employed to elucidate the mechanistic role of mitophagy in the modulation of NLRP3 inflammasome activation by dihydromyricetin.ResultsDihydromyricetin administration significantly attenuated NLRP3 inflammasome activation and vascular inflammation in mice on a high-fat diet, thereby exerting a pronounced inhibitory effect on atherogenesis. Both in vivo and in vitro, dihydromyricetin treatment markedly enhanced mitophagy. This enhancement in mitophagy ameliorated the mitochondrial damage instigated by saturated fatty acids, thereby inhibiting the activation and nuclear translocation of NF-κB. Consequently, concomitant reductions in the transcript levels of NLRP3 and interleukin-1β (IL-1β), alongside decreased activation of NLRP3 inflammasome and IL-1β secretion, were discerned. Notably, the inhibitory effects of dihydromyricetin on the activation of NF-κB and subsequently the NLRP3 inflammasome were determined to be, at least in part, contingent upon its capacity to promote mitophagy.ConclusionThis study suggested that dihydromyricetin may function as a modulator to promote mitophagy, which in turn mitigates NF-κB activity and subsequent NLRP3 inflammasome activation, thereby conferring protection against atherosclerosis.

Umbilical Vein Flows and Cardiac Size, Shape, and Ventricular Contractility in Fetuses With Estimated Weight Less-Than 10th Centile.

In a cohort of patients with estimated fetal weights (EFWs) <10th centile, we aimed 1) to compare the prevalence of abnormalities of fetal 4-chamber view (4CV) cardiac size, shape, and ventricular contractility in fetal growth restricted (FGR) and small-for-gestational-age (SGA) fetuses and 2) to compare umbilical vein flow (UVF) measurements to standard Doppler surveillance in predicting abnormalities of cardiac function. Prospective observational cohort study of fetuses with EFW <10th percentile. Measurements of size and shape used were 4CV transverse width, 4CV cardiac area, 4CV global sphericity index, and right-to-left ventricular mid-chamber width ratio. Variables of contractility used were fractional shortening change at the mid-ventricle chamber, global longitudinal strain, fractional area change, and left ventricular cardiac output. The UVF and standard Doppler surveillance including umbilical artery (UA), middle cerebral artery, and cerebroplacental ratio (CPR) were collected. Control data were from previously published studies. A total of 95 fetuses with EFWs <10th centile were included in the study. The rates of abnormalities of cardiac size and shape and ventricular contractility were all significantly elevated compared with normally grown control fetuses but similar between FGR and SGA fetuses. In a subset of 76 patients with UVF data, evaluation UVF identified more patients with any abnormality of contractility compared with UA (37.9 vs 17.2%, P = .02). The addition of UVF doubled the detection rate of ventricular contractility abnormalities. The addition of UVF should be considered in the surveillance of FGR and SGA fetuses to further stratify the severity of hypoxemia and to identify those at greater risk for future cardiovascular dysfunction.

Nitric oxide donor increases umbilical vein blood flow and fetal oxygenation in fetal growth restriction. A pilot study

IntroductionTo evaluate the maternal and fetal hemodynamic effects of treatment with a nitric oxide donor and oral fluid in pregnancies complicated by fetal growth restriction. Methods30 normotensive participants with early fetal growth restriction were enrolled. 15 participants were treated until delivery with transdermal glyceryl trinitrate and oral fluid intake (Treated group), and 15 comprised the untreated group. All women underwent non-invasive assessment of fetal and maternal hemodynamics and repeat evaluation 2 weeks later. ResultsIn the treated group, maternal hemodynamics improved significantly after two weeks of therapy compared to untreated participants. Fetal hemodynamics in the treated group showed an increase in umbilical vein diameter by 18.87 % (p < 0.01), in umbilical vein blood flow by 48.16 % (p < 0.01) and in umbilical vein blood flow corrected for estimated fetal weight by 30.03 % (p < 0.01). In the untreated group, the characteristics of the umbilical vein were unchanged compared to baseline. At the same time, the cerebro-placental ratio increased in the treated group, while it was reduced in the untreated group, compared to baseline values. The treated group showed a higher birthweight centile (p = 0.03) and a lower preeclampsia rate (p = 0.04) compared to the untreated group. DiscussionThe combined therapeutic approach with nitric oxide donor and oral fluid intake in fetal growth restriction improves maternal hemodynamics, which becomes more hyperdynamic (volume-dominant). At the same time, in the fetal circuit, umbilical vein flow increased and fetal brain sparing improved. Although a modest sample size, there was less preeclampsia and a higher birthweight suggesting beneficial maternal and fetal characteristics of treatment.

Association of umbilical vein flow with abnormal fetal growth and adverse perinatal outcome in low-risk population: multicenter prospective study.

To investigate the relationship of umbilical vein flow (UVF) measured close to term with abnormal fetal growth and adverse perinatal outcome in a cohort of pregnancies at low risk of placental insufficiency. This was a prospective multicenter observational study conducted across two tertiary maternity units. Patients with a singleton appropriate-for-gestational-age fetus between 35 and 38 weeks' gestation were included. Pregnancies at higher risk of placental insufficiency or with fetal anomalies were excluded. At ultrasound examination, the abdominal circumference (AC), umbilical vein diameter and peak velocity of the umbilical vein were measured, and, using these variables, a new variable, UVF/AC, was calculated. The primary outcome was the occurrence of severely stunted fetal growth, defined as a greater than 40-percentile drop between estimated fetal weight at the third-trimester ultrasound and birth weight. The occurrence of adverse perinatal outcome (defined as one of the following: neonatal acidosis (umbilical artery pH < 7.15 and/or base excess > 12 mmol/L) at birth, 5-min Apgar score < 7, neonatal resuscitation or neonatal intensive care unit admission) was analyzed as a secondary outcome. Between April 2021 and March 2023, 365 women were included in the study. The mean UVF/AC at enrolment was 6.4 ± 2.6 mL/min/cm, and 35 (9.6%) cases were affected by severely stunted fetal growth. Severely stunted fetal growth was associated with a lower mean UVF/AC (5.4 ± 2.6 vs 6.5 ± 2.6 mL/min/cm; P = 0.02) and a higher frequency of UVF/AC < 10th percentile (8/35 (22.9%) vs 28/330 (8.5%); P = 0.01). Moreover, UVF/AC showed an area under the receiver-operating-characteristics curve (AUC) of 0.65 (95% CI, 0.55-0.75; P = 0.004) in predicting the occurrence of severely stunted fetal growth, and the optimal cut-off value of UVF/AC for discriminating between normal and severely stunted fetal growth was 7.2 mL/min/cm. This value was associated with a sensitivity and specificity of 0.77 (95% CI, 0.60-0.90) and 0.33 (95% CI, 0.28-0.39), and positive and negative predictive values of 0.11 (95% CI, 0.07-0.15) and 0.93 (95% CI, 0.87-0.97), respectively. Regarding the occurrence of adverse perinatal outcome, this was associated independently with maternal age (adjusted odds ratio (aOR), 0.93 (95% CI, 0.87-0.99); P = 0.04), UVF/AC Z-score (aOR, 0.53 (95% CI, 0.30-0.87); P = 0.01) and augmentation of labor (aOR, 2.69 (95% CI, 1.28-5.69); P = 0.009). UVF/AC showed an AUC of 0.65 (95% CI, 0.56-0.73; P = 0.005) in predicting the occurrence of adverse perinatal outcome, and the optimal cut-off value of UVF/AC for discriminating between normal and adverse perinatal outcome was 6.7 mL/min/cm. This value was associated with a sensitivity and specificity of 0.70 (95% CI, 0.54-0.83) and 0.40 (95% CI, 0.34-0.45), and positive and negative predictive values of 0.14 (95% CI, 0.09-0.19) and 0.91 (95% CI, 0.85-0.95), respectively. Our data demonstrate an association between reduced UVF close to term, severely stunted fetal growth and adverse perinatal outcome in a cohort of low-risk pregnant women, with a moderate ability to rule out and a poor ability to rule in either outcome. Further studies are needed to establish whether the assessment of UVF can improve the identification of fetuses at risk of subclinical placental insufficiency and adverse perinatal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease

BackgroundFetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes. ObjectivesThis study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD. MethodsIn this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content. Superior vena cava (SVC) flow was used as a proxy for cerebral blood flow. Primary outcomes were 18-month mortality and Bayley Scales of Infant Development-III assessment. ResultsA total of 144 fetuses with cyanotic CHD were assessed. By 18 months, 18 patients (12.5%) died. Early mortality was associated with reduced combined ventricular output (P = 0.01), descending aortic flow (P = 0.04), and umbilical vein flow (P = 0.03). Of the surviving patients, 71 had ND outcomes assessed. Cerebral oxygen delivery was the fetal hemodynamic variable most strongly associated with cognitive, language, and motor outcomes (P < 0.05). Fetal SVC flow was also associated with cognitive, language, and motor outcomes (P < 0.01), and it remained an independent predictor of cognitive (P = 0.002) and language (P = 0.04) outcomes after adjusting for diagnosis. Diminished SVC flow also performed better than other fetal CMR and echocardiographic predictors of cognitive ND delay (receiver-operating characteristic curve area: 0.85; SE 0.05). ConclusionsAmong fetuses with cyanotic CHD, diminished fetal combined ventricular output is associated with mortality, whereas cerebral blood flow and oxygen delivery are associated with early cognitive, language, and motor development at 18 months of age. These results support the inclusion of fetal CMR to help identify patients at risk of adverse ND outcomes.

Effects of umbilical vein flow on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values. This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (<fifth centile) UVBF blood flow corrected forAC (UVBF/AC), neurosonography was performed at 33-34weeks of gestation to assess CC and CV lengths and the depth of Sylvian fissure (SF), parieto-occipital (POF) and calcarine fissures (CF). Neurosonographic variables were normalized for fetal head circumference size. The study cohort included 60 late FGR, 31 with normal UVBF/AC and 29 with abnormal UVBF/AC values. The latter group showed significant differences in CC (median (interquartile range (IQR) normal 0.96 (0.73-1.16) vs. abnormal UVBF/AC 0.60 (0.47-0.87); p<0.0001)), CV (normal 1.04 (0.75-1.26) vs. abnormal UVBF (AC 0.76 (0.62-1.18)); p=0.0319), SF (normal 0.83 (0.74-0.93) vs. abnormal UVBF/AC 0.56 (0.46-0.68); p<0.0001), POF (normal 0.80 (0.71-0.90) vs. abnormal UVBF/AC l 0.49 (0.39-0.90); p≤0.0072) and CF(normal 0.83 (0.56-1.01) vs. abnormal UVBF/AC 0.72 (0.53-0.80); p<0.029). Late onset FGR fetuses with of reduced umbilical vein flow showed shorter CC and CV length and a delayed cortical development when compared to those with normal umbilical vein hemodynamics. These findings support the existence of a link between abnormal brain development and changes in umbilical vein circulation.

Abstract 17366: Effects of Acute Maternal Supplemental Oxygen on the Fetal Circulation in Transposition of the Great Arteries

Introduction: The presence of a restrictive atrial septum in the setting of transposition of the great arteries (TGA) is associated with a high risk of hypoxic ischemic injury upon transition to postnatal circulation. Fetal cardiovascular magnetic resonance (CMR) measures of vessel flow and oxygen saturation provide a unique opportunity to study fetal TGA hemodynamics at baseline and during acute maternal hyperoxygenation. Methods: Thirty-one pregnant mothers with fetuses diagnosed with TGA and an intact ventricular septum (n=23) or small ventricular septal defect (n=8) were recruited and underwent fetal CMR in room air and during administration of 10L/min of oxygen by face mask for up to 45 minutes. Blood flow and oxygen saturations were measured in the major fetal vessels using cine phase contrast MRI and MR relaxometry at baseline and during hyperoxygenation. Results: Two patients exhibited severe restriction at the atrial septum, one undergoing fetal atrial septostomy at 37 weeks and one requiring cannulation onto ECMO shortly after birth. Both revealed reversal of the usual relationship of oxygen saturation between the aorta and the main pulmonary artery at baseline and during hyperoxygenation, i.e. in TGA with restrictive atrial septum the saturations are higher in the aorta than pulmonary. Acute maternal supplemental oxygen was associated with increased pulmonary blood flow (p=0.008) and reduced foramen ovale (p=0.01) and ductus arteriosus shunting (p=0.01). There were no significant changes in umbilical vein, descending aorta and superior vena cava flow. Fetal oxygen saturations increased throughout fetal circulation (p&lt;0.0001) with an associated increase in fetal oxygen delivery (p=0.007), but no increase in fetal cerebral oxygen delivery (p=0.58). Conclusions: This study characterized the effects of acute maternal supplemental oxygen on the fetal circulation in patients with TGA and confirmed the redistribution of flow toward the fetal pulmonary circulation. We observed higher oxygen saturations in the aorta than main pulmonary artery in fetuses with TGA with an intact or highly restrictive atrial septal communication. This finding could be helpful in selecting patients for prenatal or emergency neonatal balloon atrial septostomy.

OP05.05: Is the umbilical vein flow associated with birthweight? Multicentre prospective study in a low‐risk population

OP05.05: Is the umbilical vein flow associated with birthweight? Multicentre prospective study in a low‐risk population

The role of different Doppler parameters in predicting adverse neonatal outcomes in fetuses with late-onset fetal growth restriction.

The aim of this study is to clarify the role of different Doppler parameters such as umbilicocerebral ratio (UCR), cerebroplacentouterine ratio (CPUR), aortic isthmus, renal artery, and umbilical vein flow Doppler in predicting adverse neonatal outcomes in fetuses with late -onset fetal growth restriction. The study included all patients diagnosed with fetal growth restriction at 32-39 weeks' gestation between 01/02/2020 and 01/02/2022 and treated at the Department of Obstetrics and Gynecology, Inonu University School of Medicine. Patients included in the study had a median gestational week at delivery of 37 (minimum 33+0-maximum 39+0), median CPR of 1.42 (minimum-maximum 0.43-3.57), and median UCR of 0.7 (minimum-maximum 0.28-2.3). Receiver operating characteristic analysis was performed to determine the performance of the measured obstetric Doppler parameters in predicting the development of adverse neonatal outcomes. Umbilical venous blood flow showed the best performance in predicting adverse neonatal outcomes [area under the curve 0.952, 95% confidence interval (CI) 0.902-0.981, p<0.001]. Multivariate logistic regression analysis showed that fetuses with abnormal CPUR had a 4.5-fold (95% CI 0.084-0.583, p=0.02) increased risk of adverse neonatal outcome, whereas fetuses with abnormal umbilical venous flow had a 1.07-fold (95% CI 0.903-0.968, p<0.001) increased risk of adverse neonatal outcome. The results of this study demonstrate that the use of UCR, CPUR, umbilical venous flow, and aortic isthmus PI Doppler parameters along with umbilical artery PI and CPR are effective in predicting adverse neonatal outcomes in fetuses with late -onset fetal growth restriction.

Placental and Doppler ultrasound findings in pregnant women with SARS-CoV-2 infection

Several viral infections cause changes in the placenta. Cytomegalovirus, herpes viruses, and HIV cause increased placental thickness; Zika virus induces focal regions of necrosis; parvovirus B19 causes a structural injury. Umbilical flow can be considered a direct measurement of vascular placental function. This study aimed to compare placental ultrasound and umbilical Doppler findings in pregnant women who tested positive or negative for SARS-CoV-2. Our work aimed to confirm the suspicion of placental infection and the consequence in fetal physiopathology. Fifty-seven pregnant women who tested positive for SARS-CoV-2 at the time of or 1 month before the ultrasound scan were evaluated. Cases included 9 first trimester, 16 second trimester, and 32 third trimester ultrasound scans. For comparison, 110 pregnant women (controls) were evaluated. They included 19 women in their first trimester, 43 in their second trimester, and 48 in the third trimester. Controls were asymptomatic and tested negative for SARS-CoV-2 infection in the last 72 hours before the ultrasound scan. Fetal biometry, placental thickness, placental lakes and Doppler umbilical vein parameters, including venous cross-sectional area (mean transverse diameter and radius of umbilical vein, mean velocity of umbilical vein), and umbilical vein blood flow were evaluated. Placental thickness (in millimeter) was significantly higher in the group of pregnant women with SARS-CoV-2 infection (53.82 [10-115]) than in the control group (33.82 [12-66]; P<.001) in their second and third trimesters. The frequency of >4 placental lakes was significantly higher in the group of pregnant women with SARS-CoV-2 infection (28/57 [50.91%]) than in the control (7/110 [6.36]; P<.001) in all 3 trimesters. The mean velocity of umbilical vein was significantly higher in the group of pregnant women with SARS-CoV-2 infection (12.45 [5.73-21]) than in the control group (10.81 [6.31-18.80]; P=.001) in all 3 trimesters. Umbilical vein blood flow (in milliliter per minute) was significantly higher in the group of pregnant women with SARS-CoV-2 infection (389.9 [6.52-1496.1]) than in the control group (305.05 [3.11-1441]; P=.05) in all 3 trimesters. Significant differences in placental and venous Doppler ultrasound were documented. Placental thickness, placental venous lakes, mean velocity of umbilical vein, and umbilical vein flow were significantly higher in the group of pregnant women with SARS-CoV-2 infection in all 3 trimesters.

Altered Right Portal and Umbilical Vein Doppler Parameters in Fetal Macrosomia Resulting from Pregestational andGestational Diabetic Mothers: A Prospective Case-Control Study

Objective: To evaluate the blood flow of the umbilical vein and right portal vein in macrosomic fetuses of diabetic mothers and investigate the effect of maternal insulin treatment on these blood flows. Material and Methods: This prospective case-control study was conducted between March 2019 and December 2019. Fetuses of the 49 pregestational and gestational diabetic mothers who had an abdominal circumference percentile above 97% were evaluated as macrosomic and formed the study group. The study group was divided into two subgroups: patients treated with insulin and those who did not. In the control group, 48 non-diabetic pregnant women with matched gestational weeks whose fetuses are at the 10-90% percentile were included. Time-averaged maximum blood velocity (TAMXV) values of the right portal vein and the free loop of the umbilical vein were measured. Results: The median right portal vein TAMXV value and umbilical vein TAMXV value were found to be significantly higher in diabetic pregnancies (16.25 cm/s, and 15.28 cm/s, respectively) than in the control group (12.76 cm/s, and 13.38 cm/s, respectively, p<0.001). Umbilical and right portal vein flows were similar in macrosomic fetuses of diabetic mothers who were treated with insulin or those who did not. While umbilical vein flow in macrosomic fetuses increased as the gestational age progressed (p=0.028), it was observed steadily in normally growing fetuses. Conclusion: The umbilical and right portal vein flows are higher in macrosomic fetuses of diabetic mothers than in appropriately grown fetuses. Maternal insulin treatment does not affect fetal umbilical vein and right portal vein blood flow in macrosomic fetuses.

Correction of fetal umbilical vein flow imbalance following laser surgery for twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) is characterized by unequal hemodynamics between the twins. We aimed to assess preoperatively the difference in umbilical vein flow (UVF) between the recipient and donor monochorionic diamniotic twins and evaluate the change in UVF following laser surgery in both twins. This was a retrospective cohort study of differences in UVF that occurred following laser surgical treatment of TTTS. Sonographic assessment of the umbilical vein before and 24 h after fetoscopic laser surgery for TTTS was performed. Umbilical vein diameter and time-averaged maximum velocity were measured, and UVF per kg (UVF/kg) was converted into a Z-score by a calculator created using gestational age as an independent variable. Z-score values were converted into centiles, which were evaluated statistically. Median differences in UVF/kg centile values were adjusted for TTTS stage and presence of arterioarterial anastomoses. The study population consisted of 363 TTTS patients. The adjusted preoperative median difference in UVF/kg centile between the recipient vs donor twin was 17.9% (-17.1% to 57.6%), P < 0.0001. The adjusted median difference in UVF/kg centile between the postoperative vs preoperative period among recipients was 2.2% (-10.8% to 13.8%), P < 0.0001, while the adjusted median difference among donors was 27.3% (8.2%-34.6%), P < 0.0001. The preoperative difference in UVF between the recipient and donor twins confirms the pathophysiology of TTTS. Postoperatively, the substantial increase in UVF of the donor twin and the relatively small increase in UVF of the recipient twin confirm that ablation of the vascular communications resulted in rapid improvement in perfusion of the donor twin. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The cardiac-fetal-placental unit: fetal umbilical vein flow rate is linked to the maternal cardiac profile in fetal growth restriction

The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance. This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction. This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery. A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P<.0001), umbilical vein velocity (P=.02), umbilical vein flow (P<.0001), and umbilical vein flow corrected for fetal weight (P<.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rs=0.261), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.338) and maternal potential energy-to-kinetic energy ratio (rs=-0267). The fetal umbilical vein time averaged max velocity was positively correlated to maternal cardiac output (rs=0.189) and maternal inotropy index (rs=0.162), whereas there was a negative correlation with maternal systemic vascular resistance (rs=-0.264) and maternal potential energy-to-kinetic energy ratio (rs=-0.171). The fetal umbilical vein flow and the flow corrected for estimated fetal weight were positively correlated with maternal cardiac output (rs=0.339 and rs=0.297) and maternal inotropy index (rs=0.217 and r=0.336), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.461 and rs=-0.409) and maternal potential energy-to-kinetic energy ratio (rs=-0.336 and rs=-0.408). Maternal and fetal hemodynamic parameters were different in the 3 groups of fetuses: fetal growth restriction, small for gestational age, and adequate for gestational age. Maternal hemodynamic parameters were closely and continuously correlated with fetal hemodynamic features. In particular, a maternal hemodynamic profile with high systemic vascular resistance, low cardiac output, reduced inotropism, and hypodynamic circulation was correlated with a reduced umbilical vein flow and increased umbilical artery pulsatility index. The mother, placenta, and fetus should be considered as a single cardiac-fetal-placental unit. The correlations of systemic vascular resistance, cardiac output, and inotropy index with umbilical artery impedance indicate the key role of these 3 parameters in placental vascular tree development. The umbilical vein flow rate and, therefore, the placental perfusion seems to be influenced not only by these three parameters but also by the maternal cardiovascular kinetic energy.

Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit (n = 12; 98 ± 4 days; 743 ± 350 g). The umbilical vessels were cannulated, and fetuses were supported for 46.4 ± 46.8 h using the pumped AP versus 11 ± 13 h on the pumpless AP circuit. Upon initiation of AP support on the pumped system, we observed supraphysiologic circuit flows, tachycardia, and hypertension, while animals maintained on a pumpless AP circuit exhibited subphysiologic flows. On the pumped AP circuit, there was a progressive decline in umbilical vein (UV) flow and oxygen delivery. We conclude that the addition of a centrifugal pump to the AP circuit improves survival of preterm pigs by augmenting UV flow through the reduction of right ventricular afterload. However, we continued to observe the development of heart failure within a matter of days.

Umbilical Venous Volume Flow in Late-Onset Fetal Growth Restriction.

Umbilical vein flow (UVF) is reduced in fetal growth restriction (FGR). We compared absolute and size-adjusted UVF (estimated fetal weight [EFW] and abdominal circumference [AC]) and rates of abnormal UVF parameters (<10th percentile) among FGR fetuses meeting Delphi criteria (FGR-D) against small for gestational age (SGA) fetuses and appropriate for gestational age (AGA) controls. Absolute UVF, UVF/EFW, and UVF/AC were compared between 73 FGR pregnancies (35 FGR-D, 38 SGA) and 108 AGA controls. Rates of abnormal UVF were compared to abnormal umbilical artery pulsatility index (UAPI). Independent samples t-tests, Mann-Whitney U, odds ratio (OR), chi-squared, and Fisher's exact tests were used as appropriate. Mean absolute UVF was significantly decreased in FGR-D compared to AGA (P=.0147), but not between SGA and AGA fetuses. The incidence of both abnormal absolute UVF and UVF/AC values (<10th centile) was higher among late-onset FGR fetuses versus AGA fetuses (UVF: OR 2.7, confidence interval [CI] 1.37-5.4; UVF/AC: OR 2.73, CI 1.37-5.4). UVF was more frequently abnormal than UAPI and in only two fetuses were both Doppler values abnormal. Absolute UVF is altered in late-onset FGR, and most pronounced among FGR-D. UVF may provide additional insight into fetal compromise in those affected by growth restriction.

Effect of SARS-CoV-2 infection on fetal umbilical vein flow and cardiac function: a prospective study.

To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect umbilical vein blood flow (UVBF) and fetal cardiac function. Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. Measurements of UVBF normalized for fetal abdominal circumference (UVBF/AC), atrial area (AA) and ventricular sphericity indices (SI) were compared between the two study groups. Chi-square and Mann-Whitney U tests were sued to analyze the data. Fifty-four consecutive pregnancies complicated and 108 not complicated by SARS-CoV-2 infection were included. The median gestational age at infection was 30.2 (interquartile range [IQR] 26.2 34.1). General baseline and pregnancy characteristics were similar between pregnant women with compared to those without SARS-CoV-2 infection. There was no difference in UVBF/AC (study groups z value-0.11 vs. 0.14 control p 0.751) values between pregnancies complicated compared to those not complicated by SARS-CoV-2 infection. Likewise, there was no difference in the left and right AA (left 1.30 vs. 1.28 p=0.221 and right 1.33 vs. 1.31 p=0.324) and SI (left 1.75 vs. 1.77 p=0.208 and right 1.51 vs. 1.54 p=0.121) between the two groups. SARS-CoV-2 infection does not affect UVBF and fetal cardiac function in uncomplicated pregnancies.

Computing Z‐Score Equations for Clinical Use to Measure Fetal Umbilical Vein Size and Flow Using Six Independent Variables of Age and Size

Measurements of the umbilical vein diameter (UVD) and blood flow (mL/min) (UVF) have been demonstrated to be decreased in fetuses with growth restriction (FGR) using gestational age (GA) as the independent variable. However, no previous studies have used the biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and the estimated fetal weight (EFW) to create equations to be used for z-score computations when evaluating fetuses at risk foran abnormal UVD and UVF. Two hundred and forty normal fetuses between 20 and 40 weeks of gestation were examined in which the UVD and time averaged maximal velocity (TAMX) were measured from which the UVF, UVF/HC, UVF/AC, and UVF/kg were computed. Fractional polynomial regression analysis was used to compute z-score equations using the above independent variables. Thirty-six fetuses with abnormal growth of the AC were examined to test the validity of the equations. The UVD, TAMX, UVF, UVF/HC, and UVF/AC all increased with gestatonal age and fetal growth except for the UVF/kg, which decreased with age and growth. From the regression equations, two z-score calculators were created using an Excel spreadsheet that can be used in clinical practice. Abnormal measurements of the UVD, UVF, UVF/HC, UVF/AC, and UVF/kg were observed in the 36 study fetuses, 21 with an AC < 10th centile and 15 with an AC > 90th centile. Using the equations generated from this study and the z-score calculators provides a clinical tool to measure the size and flow of the umbilical vein that may have clinical implications.

Abstract 11766: Late Gestation Fetal Oxygenation is Associated With Birthweight and Head Circumference in Patients With Cyanotic Congenital Heart Disease

Introduction: Abnormal fetal growth and development are evident in patients with cyanotic congenital heart disease (cCHD). However, the relationship between growth and fetal oxygenation is unknown. We sought to investigate the relationship between fetal hemodynamics and fetal growth in cCHD using fetal cardiovascular Magnetic Resonance Imaging (MRI). Hypothesis: The impaired fetal oxygenation would be associated with diminished fetal brain and body growth in cCHD. Methods: We performed a prospective observational study in fetuses diagnosed with cCHD at our institution from June 2010 to January 2020. Late-gestational fetal cardiovascular MRI was performed in 152 fetuses with cCHD to assess fetal blood flow (phase-contrast MRI) and oxygen saturation (T2 oximetry) in the major fetal vessels to calculate oxygen delivery to the brain and body according to our previously published techniques. Results are provided as medians with IQR and compared with 30 gestational age-matched normal controls using Mann-Whitney U test. A Pearson’s correlation was used to examine the relationships between variables. Results: Compared with normal controls, fetuses with cCHD had significantly reduced birth weight Z-scores [-0.41 (-0.29, 0.84) vs. -0.19 (-0.46, 0.37), p = 0.03], and neonatal head circumference Z-scores [0.1 (-1.75, 0.95) vs. 0.69 (0.1, 1.79), p = 0.003]. As a combined cohort, birthweight Z-score was correlated with fetal oxygen delivery (r = 0.33, p = 0.003), umbilical vein flow (r = 0.2, p = 0.006) and oxygen saturation (r = 0.25, p = 0.02). Birth head circumference Z-score was correlated with fetal cerebral oxygen delivery (r = 0.33, p = 0.01) and ascending aorta oxygen saturation (r = 0.33, p = 0.009). We also found an inverse relationship between ascending aorta oxygen saturation and superior vena cava flow (r = -0.24, p = 0.036). Conclusions: In conclusion, we observed associations between placental function in late gestation and birthweight, as well as cerebral oxygen delivery in utero and head circumference at birth. Our findings are in keeping with the concept that cCHD impacts fetal development through abnormal circulatory physiology and placental function.

Abstract 12589: Fetoscopic Selective Laser Photocoagulation of Placental Anastomoses Leads to Early Reduction of Cardiovascular Burden in the Twin-Twin Transfusion Syndrome

Background: Twin-twin transfusion syndrome (TTTS) occurs with an incidence of 10-15% in monochorionic pregnancies. The Children’s Hospital of Philadelphia (CHOP) TTTS Cardiovascular Score (CVS) is a 20-point scale and encompasses evaluation of five domains: Recipient (R) abnormalities of 1) ventricular hypertrophy/systolic dysfunction, 2) atrioventricular valve insufficiency, 3) diastolic ventricular inflow, ductus venosus and umbilical vein flow patterns and 4) right ventricular outflow/pulmonary obstruction; Donor (D) abnormalities of 5) umbilical arterial (UA) flow. We explore the early impact of selective fetoscopic laser photocoagulation (SLPC) of placental anastomoses on fetal cardiovascular (CV) burden. Methods: Fetal echocardiograms performed prior to and one week post SLPC from 11/2012 to 6/2018 were reviewed. Pulsatility indices (PI) of the UA and middle cerebral artery (MCA), cerebroplacental ratio (CPR) and CHOP CVS elements were analyzed pre and post SLPC using paired t-tests. Results: SLPC was performed in 198 subjects; 17 excluded due to one twin demise post SLPC. Of the 181 analyzed, mean gestational age at SLPC was 19.8 (95% CI: ±0.3) weeks. Following SLPC, R demonstrated an increase in MCA PI and decrease in UA PI, with increase in CPR. D demonstrated a similar magnitude decrease in both MCA PI and UA PI, yielding no change in CPR. Following SLPC, mean CHOP CVS decreased. CHOP pre SLPC CVS was ≥6 in 62 (34%). The magnitude of change was greater in the subgroup with greater pre SLPC CV burden (CVS &gt; 6). Most common elements to improve were systolic dysfunction, tricuspid inflow, ductus venosus and umbilical vein flow patterns; least likely to improve was ventricular hypertrophy. Conclusions: Improvement in CV burden is seen as early as 1 week post SLPC, which supports acute alteration of loading conditions as contributing to the disease. Further study of the trajectory of CV alterations may provide insight into the complex mechanisms underlying TTTS.