Evaluation of umbilical venous flow volume measured using ultrasound compared to circuit flow volume in the EXTra-uterine Environment for Neonatal Development (EXTEND) system in fetal sheep.

OBJECTIVE: To compare and validate umbilical venous flow volume (UVFV) measured at the intra-abdominal portion using ultrasound with actual flow volume of umbilical vein (UV) in fetal sheep sustained on the EXTrauterine Environment for Neonatal Development (EXTEND) system. METHODS: Circuit flow volume through the oxygenator was obtained using sensors. Ultrasound derived UVFV (ml/min) was calculated as (UV diameter [cm]/2)2 × 3.14 × maximum velocity (cm/s) × 0.5 × 60, measured at approximately the mid portion between its abdominal insertion and the origin of the ductus venosus. UVFV was measured by ultrasound once daily and was compared to the average of daily circuit flow volume directly measured. RESULTS: UVFV was measured 168 times in 15 fetal sheep. The ratio of circuit flow volume to combined cardiac output remained stable within the anticipated physiological range throughout. UVFV measured by ultrasound showed good correlation to directly measured circuit flow (r = 0.72). Interclass correlation coefficients for intra-observer variability was 0.991 (95% confidence interval [CI], 0.979-0.996). CONCLUSION: UVFV measured at the intra-abdominal portion using ultrasound shows a good correlation with directly measured circuit flow volume in UV of fetal sheep on the EXTEND system. Regular incorporation of such validated UVFV measures into clinical use may offer opportunities to better understand conditions of placental dysfunction.

Use of the modified myocardial performance index for evaluating fetal cardiac functions in pregestational diabetic pregnancy babies.

The aim of this study is assessment of importance of use of the modified myocardial performance index (Mod-MPI) for the evaluation of foetal cardiac function in foetuses of women with pregestational diabetes mellitus (PDM). In this study, data of 30 pregnant patients aged 18-45 years diagnosed with PDM and 30 pregnant women aged 18-45 years with normal pregnancy and their babies were evaluated. Foetal echocardiographic and doppler measurements, foetal biometric measurements, umbilical artery and ductus venosus pulsatility indexes were measured in both PDM and control groups. The Mod-MPI was significantly higher in foetuses of PDM women. Many influences especially cardiac and postpartum complications are observed in infants of PDM women. The Mod-MPI is a simple and useful method for assessing foetal ventricular function. Our study has shown that PDM is associated with foetal ventricular dysfunction.Impact statementWhat is already known on this subject? Although MPI is frequently used in routine clinical assessment of neonates, it is not used adequately in foetuses. Many influences especially cardiac and postpartum complications are observed in infants of PDM women. However, there are few studies focussed specifically on the assessment of foetal cardiac function in PDM.What do the results of this study add? MPI, which shows both diastolic and systolic functions is independent of ventricular anatomy and foetal heart rate, was found significantly higher in diabetic mother foetuses, can be said to be a valuable parameter in evaluating foetal cardiac functions globally.What are the implications of these findings for clinical practice and/or further research? Our study has shown that foetuses PDM are associated with foetal ventricular dysfunction. For this MPI measurement can be routinely performed at foetal cardiac measurements in foetuses of PDM mothers.

Diagnosing Small for Gestational Age during second trimester routine screening: Early sonographic clues.

OBJECTIVE: Small for gestational age (SGA) is generally defined as birth weight being at or below the 10th percentile. Children with SGA have a higher risk for complications. There is a need for early predictors, as the accurate diagnosis rate is only 50%. In the current study, we aimed to evaluate diagnostic performance of ultrasound (US)/color Doppler ultrasound (CDUS) parameters (umbilical vein-UV, right portal vein-RPV diameter/flow rate, and portal sinus-PS diameter) examined at 20-22 gestational week as SGA diagnostic factors. MATERIALS AND METHODS: 93 pregnant included (32 SGA, 61 controls). All the US examinations were performed between 20 and 22 weeks of gestation. UV, RPV, and PS measurements were performed by using the same image acquired for abdominal circumference measurement. A fetus with as estimated fetal weight (EFW) below the 10th percentile was diagnosed as SGA and SGA at birth was defined as having a birth weight under the 10th percentile. RESULTS: Pregnant women in the SGA group were significantly older (30 ± 4.8 vs. 26.6 ± 5.4 years, p < 0.01). Median UV diameter was significantly lower in SGA group (2.20 vs. 2.40 mm, p = 0.001). Median RPV diameter was significantly lower in SGA group (2 vs. 2.10 mm, p = 0.018). Median PS diameter was significantly lower in SGA group (2 vs. 20.10 mm, p = 0.008). CONCLUSION: UV, RPV, and PS diameters can be earlier predictors for SGA diagnosis. Routinely evaluation of these parameters during second trimester screening can increase SGA diagnosis rates and serve for early diagnose.

Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function.

: Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.

Role of first-trimester umbilical vein blood flow in predicting large-for-gestational age at birth.

OBJECTIVES: To describe umbilical vein (UV) hemodynamics at 11 + 0 to 13 + 6 weeks of gestation in pregnancies delivering a large-for-gestational-age (LGA) neonate, and to build a multiparametric model, including pregnancy and ultrasound characteristics in the first trimester, that is able to predict LGA at birth. METHODS: This was a matched case-control study, of singleton pregnancies that underwent ultrasound examination at 11 + 0 to 13 + 6 weeks for aneuploidy screening, at a single center over a 4-year period. Cases were women who delivered a neonate with birth weight (BW) > 90th centile for gestational age and sex, according to local birth-weight standards, while controls were those who delivered a neonate with BW ranging between the 10th and 90th centiles, matched for maternal and gestational age, at a ratio of 1:3. Each included case underwent Doppler assessment of the uterine arteries and UV, including measurement of its diameter, time-averaged maximum velocity (TAMXV) and UV blood flow (UVBF). UVBF and its components were expressed as Z-scores. Fisher's exact test and Mann-Whitney U-test were used to compare differences in maternal biomarkers and ultrasound characteristics between pregnancies complicated by LGA and controls. Logistic regression and receiver-operating-characteristics (ROC) curve analyses were carried out to identify independent predictors of LGA and to build a multiparametric prediction model integrating different maternal, pregnancy and ultrasound characteristics. Subgroup analysis was also performed, considering women who delivered a neonate with BW > 4000 g. RESULTS: In total, 964 pregnancies (241 with LGA at birth and 723 without) were included in the study. In LGA pregnancies compared with controls, UV-TAMXV Z-score (0.8 (interquartile range (IQR), 0.4-1.5) vs 0.0 (IQR, -0.3 to 0.5); P ≤ 0.001) and UVBF Z-score (1.3 (IQR, 0.8-1.9) vs 0.1 (IQR, -0.4 to 0.4); P ≤ 0.001) were higher, while there was no difference in median UV diameter Z-score (P = 0.56). Median uterine artery pulsatility index multiples of the median (MoM; 0.94 (IQR, 0.78-1.12) vs 1.02 (IQR, 0.84-1.19); P = 0.04) was significantly lower in LGA pregnancies. On multivariate logistic regression analysis, maternal body mass index (BMI; adjusted odds ratio (aOR), 1.2 (95% CI, 1.1-1.7); P < 0.001), parity (aOR, 1.4 (95% CI, 1.2-1.6); P < 0.001), pregnancy-associated plasma protein-A (PAPP-A) MoM (aOR, 1.1 (95% CI, 1.0-1.6); P = 0.04) and UVBF Z-score (aOR, 1.6 (95% CI, 1.1-1.9); P < 0.001) were associated independently with LGA. A multiparametric model integrating parity, BMI and PAPP-A MoM provided an area under the ROC curve (AUC) of 0.72 (95% CI, 0.67-0.76) for the prediction of LGA. The addition of UVBF Z-score to this model significantly improved the prediction of LGA provided by maternal and biochemical factors, with an AUC of 0.79 (95% CI, 0.75-0.83; P = 0.03). Similarly, the model incorporating UVBF Z-score predicted BW > 4000 g with an AUC of 0.83 (95% CI, 0.75-0.93). CONCLUSIONS: UVBF measured at the time of the 11-14-week scan is associated independently with, and is predictive of, LGA and BW > 4000 g. Adding measurement of UVBF to a multiparametric model that includes maternal (parity and BMI) and biochemical (PAPP-A) parameters improves the diagnostic accuracy of prenatal screening for LGA at birth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Screening performance of congenital heart defects in first trimester using simple cardiac scan, nuchal translucency, abnormal ductus venosus blood flow and tricuspid regurgitation.

OBJECTIVE: The objective of this study was to analyze if the addition of simple cardiac scan in cases with increased nuchal translucency (NT) and/or abnormal ductus venosus (DV) blood flow, and/or tricuspid regurgitation (TCR) can improve detection of congenital heart defects (CHD) in chromosomally normal fetuses without non-cardiac defects at 11-13 + 6 gestational weeks in a population of singleton pregnancies. METHODS: During the 10 years period, all singleton pregnancies at 11-13 + 6 weeks were routinely scanned for NT, DV blood flow and TCR assessment and, if a single of these parameters was abnormal, simple cardiac scan with 2D gray scale and color and/or directional power Doppler in 4-chamber (4-CV) and 3 vessel and trachea views (3VTV) was performed. RESULTS: The sensitivity and specificity of NT ≥ 95th + DV R/A a-wave + TCR in detecting CHD were 77% and 97%, respectively, and of simple cardiac scan, 67% and 98%, respectively. Area under the curve of receiver operating characteristic curve of NT ≥ 95th + DV R/A a-wave + TCR was 0.838, and of NT ≥ 95th + DV R/A a-wave + TCR + simple cardiac scan was 0.915. CONCLUSIONS: In chromosomally normal fetuses without non-cardiac anomalies, addition of simple cardiac scan to the combined first trimester screening parameters improves detection of major CHD during first trimester.

Umbilical Venous Catheters and Peripherally Inserted Central Catheters: Are They Equally Safe in VLBW Infants? A Non-Randomized Single Center Study.

Background and Objective: Peripherally inserted central catheters (PICC) and umbilical venous catheters (UVC) are frequently used for vascular access in neonatal intensive care units (NICUs). While there is a significant need for these devices for critically ill neonates, there are many complications associated with their use. We aimed at investigating the incidence of UVC and PICC complications in very low birth weight (VLBW) infants. Materials and Methods: This is an observational study performed with neonates of the tertiary General Hospital of Piraeus, Greece, during an 18 month-period. Seventy-one neonates were recruited and divided into two groups: 34 neonates with PICC and 37 neonates with UVC. We recorded: Catheter dwell time, the causes of catheter removal, other complications, infections, and catheter tip colonization rates. Results: No significant statistical differences were noticed between the 2 study groups with regards to demographic characteristics, causes for catheter removal, catheter indwelling time or the incidence of nosocomial infection. Eleven UVC tips and no PICC tips were proved colonized (p = 0.001) following catheter removal. Conclusions: The incidence of complications associated with the use of UVCs and PICCs in VLBW infants did not significantly differ in our study. Their use seems to be equally safe. Further studies, with larger samples, are necessary to confirm our results.

Ductus Venosus Agenesis as a Marker of Pallister-Killian Syndrome.

The ductus venosus (DV) is a shunt that allows the direct flow of well-oxygenated blood from the umbilical vein (UV) to the coronary and cerebral circulation through the foramen ovale. Its agenesis has been associated with chromosomal abnormalities and rare genetic syndromes, structural defects, intrauterine growth restriction (IUGR) and even antepartum fetal demise. Pallister-Killian Syndrome (PKS) is a rare sporadic disorder with specific tissue mosaic distribution of an extra 12p isochromosome (i(12p)). Its main clinical features are moderate to severe intellectual disability/neuromotor delay, skin pigmentation abnormalities, typical facial appearance, variable association with multiple congenital malformations and epilepsy. Though prenatal findings (including congenital diaphragmatic hernia, ventriculomegaly, congenital heart disease, polyhydramnios, and rhizomelic shortening) have been described in literature, prenatal diagnosis is difficult as there are no associated identification signs no distinctive or pathognomonic signs, and some of these malformations are hard to identify prenatally. The tissue mosaicism linked to this syndrome and the decrease of the abnormal clone carrier of the i(p12) after successive trypsinizations of cultured cells makes the diagnosis even more challenging. We present the case of a 27.5 weeks pregnant woman with a fetal ductus venosus agenesis (DVA) as the main guide marker. To our knowledge this is the first case published in literature reporting a DVA as a guide sign to diagnose a complex condition as Pallister-Killian syndrome. We also underscore the key role of new genetic techniques as microarrays to avoid misdiagnosis when only a subtle sonographic sign is present in complex conditions like this.

Neonates from women with pregestational maternal obesity show reduced umbilical vein endothelial response to insulin.

OBJECTIVE: Pregestational maternal obesity (PGMO) associates with foetoplacental vascular endothelial dysfunction and higher risk for insulin resistance in the neonate. We characterised the PGMO consequences on the insulin response of the human foetoplacental vasculature. METHODS: Umbilical veins were from pregnancies where the mother was with PGMO (body mass index 30-42.3 kg/m2, n = 33) or normal pregestational weight (PGMN) (body mass index 19.5-24.4 kg/m2, n = 21) with total gestational weight gain within the physiological range. Umbilical vein ring segments were mounted in a myograph for isometric force measurements. Primary cultures of human umbilical vein endothelial cells were used in passage 3. Vessel rings and cells were exposed to 1 nmol/L insulin (20 min) in the absence or presence of 100 µmol/L NG-nitro-l-arginine methyl ester (inhibitor of nitric oxide synthase, NOS). RESULTS: Vessel rings from PGMO showed reduced nitric oxide synthase-activity dependent dilation to insulin or calcitonin-gene related peptide compared with PGMN. PGMO associated with higher inhibitor phosphorylation of the insulin receptor substrate 1 (IRS-1) and lower activator phosphorylation of protein kinase B/Akt (Akt). Cells from PGMO also showed lower nitric oxide level and reduced activator serine1177 but increased inhibitor threonine495 phosphorylation of endothelial nitric oxide synthase (eNOS) and saturable transport of l-arginine. HUVECs from PGMO were not responsive to insulin. CONCLUSION: The lack of response to insulin by the foetoplacental endothelium may result from reduced IRS-1/Akt/eNOS signalling in PGMO. These findings may result in higher risk of insulin resistance in neonates to PGMO pregnancies.

Hemodynamic factors associated with fetal cardiac remodeling in late fetal growth restriction: a prospective study.

Background Altered cardiac geometry affects a proportion of fetuses with growth restriction (FGR). The aim of this study was to explore the hemodynamic factors associated with cardiac remodeling in late FGR. Methods This was a prospective study of singleton pregnancies complicated by late-onset FGR undergoing assessment of left (LV) and right (RV) ventricular sphericity-index (SI). The study population was divided in two groups according to the presence of cardiac remodelling, defined as LVSI <5th centile. The following outcomes were explored: gestational age at birth, birthweight, caesarean section (CS) for fetal distress, umbilical artery (UA) pH and neonatal admission to special care unit. The differences between the 2 groups in UA pulsatility index (PI), middle cerebral artery (MCA) PI, uterine artery PI, cerebroplacental ratio (CPR) and umbilical vein (UV) flow corrected for fetal abdominal circumference (UVBF/AC) were tested. Results In total, 212 pregnancies with late FGR were enrolled in the study. An abnormal LV SI was detected in 119 fetuses (56.1%). Late FGR fetuses with cardiac remodeling had a lower birthweight (2390 g vs. 2490; P = 0.04) and umbilical artery pH (7.21 vs. 7.24; P = 0.04) and were more likely to have emergency CS (42.8% vs. 26.9%; P = 0.023) and admission to special care unit (13.4% vs. 4.3%; P = 0.03) compared to those with normal LVSI. No difference in either UA PI (p = 0.904), MCA PI (P = 0.575), CPR (P = 0.607) and mean uterine artery PI (P = 0.756) were present between fetuses with or without an abnormal LV SI. Conversely, UVBF/AC z-score was lower (-1.84 vs. -0.99; P ≤ 0.001) in fetuses with cardiac remodeling and correlated with LV (P ≤ 0.01) and RV SI (P ≤ 0.02). Conclusion Fetal cardiac remodelling occurs in a significant proportion of pregnancies complicated by late FGR and is affected by a high burden of short-term perinatal compromise. The occurrence of LV SI is independent from fetal arterial Dopplers while it is positively associated with umbilical vein blood flow.

Altered development of fetal liver perfusion in pregnancies with pregestational diabetes.

BACKGROUND: Pregestational diabetes is associated with fetal macrosomia, and umbilical perfusion of the fetal liver has a role in regulating fetal growth. We therefore hypothesized that pregestational diabetes alters fetal liver blood flow depending on degree of glycemic control. METHODS: In a prospective study, 49 women with pregestational diabetes underwent monthly ultrasound examinations during 24-36 gestational weeks. Blood flow was determined in the umbilical vein, ductus venosus and portal vein, and blood velocity was measured in the left portal vein, the latter reflecting the watershed between splanchnic and umbilical flow. The measurements were compared with reference values by z-score statistics, and the effect of HbA1c assessed. RESULTS: The umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p<0.001) and left portal vein blood velocity (z-score 0.64, p<0.001), were higher in the study group. Normalized portal venous flow was lower (z-score -0.42, p = 0.002), and normalized total venous liver flow tended to be lower after 30 gestational weeks (z-score -0.54, p = 0.047) in the diabetic pregnancies compared with reference values from a low-risk population. The left portal vein blood velocity was positively, and the portal fraction of total venous liver flow negatively correlated with first trimester HbA1C. CONCLUSIONS: In spite of increased umbilical blood distribution to the fetal liver, graded according to glycemic control, the total venous liver flow did not match third trimester fetal growth in pregnancies with pregestational diabetes, thus contributing towards increased perinatal risks and possibly altered liver function with long-term metabolic consequences.

Arginine bioavailability and endothelin-1 system in the regulation of vascular function of umbilical vein endothelial cells from intrauterine growth restricted newborns.

BACKGROUND AND AIMS: Intrauterine growth restriction (IUGR) is a major risk factor for perinatal morbidity and mortality, leading to long-term adverse cardiovascular outcomes. The present study aimed to investigate the potential mechanisms in IUGR-associated vascular endothelial dysfunction. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were derived from IUGR or normal newborns. We found that the proliferation of IUGR-derived HUVECs was accelerated compared to those from normal subjects. Gene profiles related to vascular function including vasomotion, oxidative stress, and angiogenesis were dysregulated in IUGR-HUVECs. Compared with HUVECs from normal newborns, nitric oxide (NO) production was reduced, with imbalance between endothelial nitric oxide synthase (eNOS) and arginase-2 (Arg-2) in IUGR. Meanwhile, intracellular asymmetric dimethylarginine (ADMA) level was elevated with diminished dimethylarginine dimethylaminohydrolase 1 (DDAH1) expression in IUGR-HUVECs. Furthermore, endothelin-1 (ET-1) and hypoxia-inducible factor 1α (HIF-1α) expression were increased, and endothelin receptor type-B (ETBR) was reduced in the IUGR group. IUGR-HUVECs exposed to hypoxia increased the ratio of ADMA to l-arginine, HIF-1α and protein arginine methyltransferase 1 (PRMT1) expression compared to controls. CONCLUSIONS: The present study demonstrated that the reduction of NO bioavailability and release results from elevated Arg-2, accumulation of intracellular ADMA, and imbalance of ET-1 and ETBR, further leading to IUGR-associated vascular endothelial dysfunction. Our study provides novel evidence on the mechanism underlying fetal programming associated with IUGR, which will serve as potential therapeutic targets in the prevention of adverse cardiovascular consequences in adulthood.

Neonatal Micro-RNA Profile Determines Endothelial Function in Offspring of Hypertensive Pregnancies.

Offspring of hypertensive pregnancies are at increased risk of developing hypertension in adulthood. In the neonatal period they display endothelial cell dysfunction and altered microvascular development. MicroRNAs, as important endothelial cellular regulators, may play a role in this early endothelial dysfunction. Therefore we identified differential microRNA patterns in endothelial cells from offspring of hypertensive pregnancies and determined their role in postnatal vascular cell function. Studies were performed on human umbilical vein endothelial cell (HUVECs) samples from 57 pregnancies. Unbiased RNA-sequencing identified 30 endothelial-related microRNAs differentially expressed in HUVECs from hypertensive compared to normotensive pregnancies. Quantitative reverse transcription PCR (RT-qPCR) confirmed a significant higher expression level of the top candidate, miR-146a. Combined miR-146a targeted gene expression and pathway analysis revealed significant alterations in genes involved in inflammation, angiogenesis and immune response in the same HUVECs. Elevated miR-146a expression level at birth identified cells with reduced ability for in vitro vascular tube formation, which was rescued by miR-146a inhibition. In contrast, miR-146a overexpression significantly reduced vascular tube formation in HUVECs from normotensive pregnancies. Finally, we confirmed that mir146a levels at birth predicted in vivo microvascular development during the first three postnatal months. Offspring of hypertensive pregnancy have a distinct endothelial regulatory microRNA profile at birth, which is related to altered endothelial cell behaviour, and predicts patterns of microvascular development during the first three months of life. Modification of this microRNA profile in vitro can restore impaired vascular cell function.

Case 253: Thrombosed Umbilical Venous Varix in an Infant.

History A 3-month-old previously healthy girl presented to an outside institution with a 4-day history of low-grade fever, irritability, and a tender "knot" in the upper abdomen. Ultrasonography (US) was performed at an outside hospital. US images were not available for review; however, they showed a mass in the left hepatic lobe, per the outside report, and the patient was referred to our institution for further evaluation. Her parents reported a normal full-term pregnancy, with regular prenatal care and normal prenatal US findings. The baby was born after an uncomplicated gestation. She was delivered at term via an uncomplicated cesarean section due to a maternal history of cesarean section. The perinatal course was uncomplicated, and there was no history of umbilical catheterization, per the parents. On arrival at our institution, the patient had a temperature of 38.2°C. All other vital signs were normal. Palpation revealed a tender and firm mass in the periumbilical region; otherwise, physical examination findings were normal. Results of laboratory work-up were normal, except for elevated white blood cell count (26 600/mm3 [26.6 × 109/L]; normal, 6000-17 500/mm3 [6-17.5 × 109/L]). The patient underwent US followed by intravenous contrast material-enhanced (10 mL ioversol, Optiray 320; Medtronic, Santa Rosa, Calif) computed tomography (CT) on the same day.

Characterization of the hemodynamic wall shear stresses in human umbilical vessels from normal and intrauterine growth restricted pregnancies.

Significant reductions in blood flow and umbilical diameters were reported in pregnancies affected by intrauterine growth restriction (IUGR) from placental insufficiency. However, it is not known if IUGR umbilical blood vessels experience different hemodynamic wall shear stresses (WSS) compared to normal umbilical vessels. As WSS is known to influence vasoactivity and vascular growth and remodeling, which can regulate flow rates, it is important to study this parameter. In this study, we aim to characterize umbilical vascular WSS environment in normal and IUGR pregnancies, and evaluate correlation between WSS and vascular diameter, and gestational age. Twenty-two normal and 21 IUGR pregnancies were assessed via ultrasound between the 27th and 39th gestational week. IUGR was defined as estimated fetal weight and/or abdominal circumference below the 10th centile, with no improvement during the remainder of the pregnancy. Vascular diameter was determined by 3D ultrasound scans and image segmentation. Umbilical artery (UA) WSS was computed via computational flow simulations, while umbilical vein (UV) WSS was computed via the Poiseuille equation. Univariate multiple regression analysis was used to test for the differences between normal and IUGR cohort. UV volumetric flow rate, UA and UV diameters were significantly lower in IUGR fetuses, but flow velocities and WSS trends in UA and UV were very similar between normal and IUGR groups. In both groups, UV WSS showed a significant negative correlation with diameter, but UA WSS had no correlation with diameter, suggesting a constancy of WSS environment and the existence of WSS homeostasis in UA, but not in UV. Despite having reduced flow rate and vascular sizes, IUGR UAs had hemodynamic mechanical stress environments and trends that were similar to those in normal pregnancies. This suggested that endothelial dysfunction or abnormal mechanosensing was unlikely to be the cause of small vessels in IUGR umbilical cords.

Postnatal dilatation of umbilical cord vessels and its impact on wall integrity: Prerequisite for the artificial placenta.

INTRODUCTION: A lung assist device, which acts as an artificial placenta, can provide additional gas exchange for preterm and term newborns with respiratory failure. The concept of the lung assist device requires a large bore access via umbilical vessels to allow pumpless extracorporeal blood flow rates up to 30 mL/kg/min. After birth, constricted umbilical vessels need to be reopened for vascular access. The objective is to study the impact of umbilical vessel expansion on vessel integrity for achieving large bore access. METHODS: Umbilical cords from healthy term deliveries were cannulated and dilatated with percutaneous transluminal angioplasty catheters in 1 mm increments from 4 to 8 mm for umbilical artery and from 4 to 15 mm for umbilical vein, n = 6 per expansion diameter. Paraffin-embedded transverse sections of dilated and control samples were HE & Van Gieson stained. Effects of dilatation, shown by splitting, were measured. RESULTS: Umbilical vessel expansion led to concentric splitting, shown by areas devoid of extracellular matrix and nuclei in the tunica intima and media. No radial splitting was observed. Results suggest an expansion threshold of umbilical artery at 6 mm and umbilical vein at 7 mm, while maximal splitting was observed above this threshold (3.6 ± 0.8%, p = 0.043 for umbilical artery 7 mm and 6.3 ± 1.8%, p = 0.048 for umbilical vein 8 mm). Endothelial cell sloughing was present in all dilated samples but not in the control samples. CONCLUSION: The suggested thresholds for safe expansions are similar to in utero umbilical vessel diameters and demonstrate a proof of concept for attaining large bore access for the lung assist device.

Risk of fetal death in growth-restricted fetuses with umbilical and/or ductus venosus absent or reversed end-diastolic velocities before 34 weeks of gestation: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to establish the risk of fetal death in early-onset growth-restricted fetuses with absent or reversed end-diastolic velocities in the umbilical artery or ductus venosus. DATA SOURCES: A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, or German using the databases PubMed, ISI Web of Science, and SCOPUS, without publication time restrictions. STUDY ELIGIBILITY CRITERIA: The study criteria included observational cohort studies and randomized controlled trials of early-onset growth-restricted fetuses (diagnosed before 34 weeks of gestation), with information on the rate of fetal death occurring before 34 weeks of gestation and absent or reversed end-diastolic velocities in the umbilical artery and/or ductus venosus. STUDY APPRAISAL AND SYNTHESIS METHODS: For quality assessment, 2 reviewers independently assessed the risk of bias using the Newcastle-Ottawa Scale for observational studies and the Cochrane Collaboration's tool for randomized trials. For the meta-analysis, odds ratio for both fixed and random-effects models (weighting by inverse of variance) were used. Heterogeneity between studies was assessed using tau2, χ2 (Cochrane Q), and I2 statistics. Publication bias was assessed by a funnel plot for meta-analyses and quantified by the Egger method. RESULTS: A total of 31 studies were included in this meta-analysis. The odds ratios for fetal death (random-effects models) were 3.59 (95% confidence interval, 2.3-5.6), 7.27 (95% confidence interval, 4.6-11.4), and 11.6 (95% confidence interval, 6.3-19.7) for growth-restricted fetuses with umbilical artery absent end-diastolic velocities, umbilical artery reversed end-diastolic velocities, and ductus venosus absent or reversed end-diastolic velocities, respectively. There was no substantial heterogeneity among studies for any of the analyses. CONCLUSION: Early-onset growth-restricted fetuses with either umbilical artery or ductus venosus absent or reserved end-diastolic velocities are at a substantially increased risk for fetal death.

Evaluation of Umbilical Vein Blood Volume Flow in Preeclampsia by Angle-Independent 3D Sonography.

OBJECTIVES: To investigate the association between umbilical vein blood volume flow and the condition of preeclampsia in an at-risk maternal patient cohort. Umbilical vein volume flow was quantified by a 3-dimensional (3D) sonographic technique that overcomes several limitations of standard sonographic flow measurement methods. METHODS: A total of 35 patients, each with a singleton pregnancy, were recruited to provide 5 patients with preeclampsia, derived as a subset from a 26-patient at-risk group, and 9 patients with normal pregnancies. An ultrasound system equipped with a 2.0-8.0-MHz transducer was used to acquire multivolume 3D color flow and power mode data sets to compute the mean umbilical vein volume flow in patients with normal pregnancies and preeclampsia. RESULTS: The gestational ages of the pregnancies ranged from 29.7 to 34.3 weeks in the patients with preeclampsia and from 25.9 to 34.7 weeks in the patients with normal pregnancies. Comparisons between patients with normal pregnancies and those with preeclampsia showed weight-normalized flow with a moderately high separation between groups (P = .11) and depth-corrected, weight-normalized flow with a statistically significant difference between groups (P = .035). Umbilical vein volume flow measurements were highly reproducible in the mean estimate, with an intrapatient relative SE of 12.1% ± 5.9% and an intrameasurement relative SE of 5.6% ± 1.9 %. In patients who developed pregnancy-induced hypertension or severe pregnancy-induced hypertension, umbilical vein volume flow suggested gestational hypertensive disorder before clinical diagnosis. CONCLUSIONS: Results indicate that mean depth-corrected, weight-normalized umbilical vein volume flow is reduced in pregnancies complicated by preeclampsia and that volume flow may indicate hypertensive disorder earlier in gestation. Volume flow measurements are highly reproducible, and further study in a larger clinical population is encouraged to determine whether 3D volume flow can complement the management of preeclampsia and, in general, at-risk pregnancy.

Acardiac twin pregnancies part IV: Acardiac onset from unequal embryonic splitting simulated by a fetoplacental resistance model.

BACKGROUND: Benirschke postulated that acardiac twinning occurs when markedly unequal embryonic splitting combines with arterioarterial (AA) and venovenous placental anastomoses. We tested this hypothesis by model simulations and by comparison of outcomes with 18 "pseudo-" (twin fetus with beating heart but otherwise with clear signs of an acardiac) and 3 "normal" acardiac cases. METHODS: The smaller/larger cell volume ratio at embryonic splitting becomes the smaller/larger embryonic/fetal blood volume ratio (a). From a, we derived nonpulsating blood pressures using normal values (larger twin) and normal values at an appropriate earlier gestational age (smaller twin). These unequal pressure sources were used in a linear resistance fetoplacental network to calculate umbilical venous diameter ratios. Acardiac onset occurs when the smaller twin has 50% left of its normal, singleton placenta. Comparison with clinical cases approximated a by crown-rump-length-ratio to the 3rd power. Input parameters are a and the AA-radius at 40 weeks. RESULTS: Acardiacs can be small or large, can occur early or late, earlier at smaller a and larger AA, with larger umbilical venous diameter ratios at smaller a and smaller AA. Comparison with the 21 clinical cases was good, except for 2. CONCLUSION: Our analysis supports Benirschke's hypothesis. The smaller twin has to share its placental perfusion with the larger twin, which is a novel finding. The AA size is essential for the future of both fetuses but complicates easy understanding of (pseudo-)acardiac clinical presentations. Late acardiac onset occurs infrequently. Using nonpulsating circulations may have caused our extensive predictions of late onset. An improved model requires including hypoxemia in the smaller twin from chronic placental hypoperfusion. Birth Defects Research 109:211-223, 2017. © 2016 Wiley Periodicals, Inc.