Enhancing electrical conductivity and mechanical properties of decellularized umbilical cord arteries using graphene coatings.

Traditional decellularized bioscaffolds possessing intact vascular networks and unique architecture have been extensively studied as conduits for repairing nerve damage. However, they are limited by the absence of electrical conductivity, which is crucial for proper functioning of nervous tissue. This study focuses on investigating decellularized umbilical cord arteries by applying coatings of graphene oxide (GO) and reduced graphene oxide (RGO) to their inner surfaces. This resulted in a homogeneous GO coating that fully covered the internal lumen of the arteries. The results of electrical measurements demonstrated that the conductivity of the scaffolds could be significantly enhanced by incorporating RGO and GO conductive sheets. At a low frequency of 0.1 Hz, the electrical resistance level of the coated scaffolds decreased by 99.8% with RGO and 98.21% with GO, compared with uncoated scaffolds. Additionally, the mechanical properties of the arteries improved by 24.69% with GO and 32.9% with RGO after the decellularization process. The GO and RGO coatings did not compromise the adhesion of endothelial cells and promoted cell growth. The cytotoxicity tests revealed that cell survival rate increased over time with RGO, while it decreased with GO, indicating the time-dependent effect on the cytotoxicity of GO and RGO. Blood compatibility evaluations showed that graphene nanomaterials did not induce hemolysis but exhibited some tendency toward blood coagulation.

Epigenetic regulation by hypoxia, N-acetylcysteine and hydrogen sulphide of the fetal vasculature in growth restricted offspring: A study in humans and chicken embryos.

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N-acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth-restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near-term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ-lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third-order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third-to-fourth order chorionic arteries from FGR pregnancies and in third-order femoral arteries from hypoxic chicken embryos. This NAC-induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3 methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. KEY POINTS: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction. We investigated the effects between N-acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos. Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature. Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy.

Ultrasound parameters of arteries and heart in normal fetuses.

BACKGROUND: Currently, no normal ultrasound data of the fetuses during the 20-40 gestation have been obtained for references of fetal growth and development. If such ultrasound data existed for prenatal diagnosis of possible diseases and abnormalities, neonates would be able to get timely treatment immediately after birth. This study was thus performed to obtain ultrasound parameters of normal fetuses during the 20-40 week gestation and the distribution of ultrasound parameters with the gestational age for references of detecting potential fetal diseases and abnormalities. METHODS: Normal fetuses without any abnormalities were enrolled, and the ultrasound parameters of the general biology, arteries, and aorta were measured and analyzed. RESULTS: 417 normal fetuses were enrolled. A significant (P < 0.05) negative correlation with the gestational age was detected in the peak systolic velocity/peak diastolic velocity (S/D), pulsatility index (PI) and resistance index (RI) of the umbilical artery (UA). A relatively stable relationship with the gestational age was detected in the fetal weight%, S/D, PI and RI of the middle cerebral artery (MCA), peak systolic velocity (PSV) and velocity time integral (VTI) of the intra-abdominal UA, fetal heart to chest ratio, mitral valve (MV)- and tricuspid valve (TV)-E/A peak flow velocity, aortic isthmic Z-score and displacement, distance between the brachiocephalic artery-left common carotid artery (BA-LCCA) and LCCA-left subclavian artery (LSA), Z-score of aorta, ascending aorta (AAO), pulmonary artery (PA), main pulmonary artery (MPA), and descending aorta (DAO). A significant (P < 0.05) positive correlation with the gestational age was detected in the fetal biological data, MCA PSV and VTI, free-UA PSV and VTI and cardio-thoracic ratio, cardiac parameters, ductus arteriosus (DA) and isthmus diameter, aortic parameters, PA and MPA diameter, MPA PSV and VTI, isthmus flow volume and velocity and PA flow volume, DA and BA parameters, and LCCA and LSA parameters (flow volume, PSV, and VTI). CONCLUSION: A certain correlation and distribution trend is detected in the ultrasound parameters of normal fetuses, and the ratios among different parameters remain relative stable. These findings can be used for determination of abnormal growth of the fetuses in prenatal ultrasound scan.

The significance of Syndecan 1, a new marker for endothelial dysfunction, in cases of fetal growth retardation.

PROBLEM: In the current study we aimed to investigate Syndecan 1 (SDC1) levels in pregnant women diagnosed with fetal growth restriction (FGR) and the relationship between SDC1 levels and clinical and doppler parameters in FGR cases associated with endothelial dysfunction, angiogenesis and uteroplacental insufficiency METHOD OF STUDY: A total of 90 pregnant women included in the study, (45 with FGR, 45 healthy control) matched by week of gestation and maternal age. Venous blood samples were collected and plasma concentrations of SDC1 were determined by a specific immunoassay. Doppler examination was performed to evaluate the relationship between the SDC1 levels and placental blood supply. RESULTS: Doppler parameters; mean UtA-PI (p < .001), CPR (p = .002) and CPUR (p < .001) were different between the groups, however MCA PI, umbilical artery PI and umbilical artery S/D were not (p > .05). While gestational age at delivery, birth weight, APGAR score at 1 and 5 min were significantly lower (all, p < .001) in the study group, non-reassure fetal heart rate tracing (p = .09) and NICU admission (p = .02) were significantly higher. SDC 1 level was 2,00 ± 1,47 ng/mL and 2,34 ± 1,12 ng/mL in the FGR and control groups, respectively (p = .008). In the study group SDC 1 level was 1,69 ± 2,00 in those with gestational age below 32 weeks and 2,13 ± 1,18 in those with gestational age above 32 weeks and there was a statistically significant difference between the groups (p = .015). Plasma SDC 1 concentration of 2,1850 ng/mL or less had a sensitivity of 70%, a specificity of 72%, area under the ROC curve .65 (p < .005). CONCLUSIONS: Low maternal plasma SDC1 level may be associated with placental insufficiency and FGR. Low levels of SDC1 may be helpful as a predictor for the development of FGR during gestation.

Vascular contraction of umbilical arteries of pregnant women with preeclampsia.

Objective: Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium channels (Katp) has been linked to preeclampsia. Activation of Katp induces vasodilation; however, no previous study has been conducted to evaluate the effects of the inhibition of these channels in the contractility of preeclamptic arteries. Glibenclamide is an oral antihyperglycemic agent that inhibits Katp and has been widely used in vascular studies. Methods: To investigate the effects of the inhibition of Katp, umbilical arteries of preeclamptic women and women with healthy pregnancies were assessed by vascular contractility experiments, in the presence or absence of glibenclamide. The umbilical arteries were challenged with cumulative concentrations of potassium chloride (KCl) and serotonin. Results: There were no differences between the groups concerning the maternal age and gestational age of the patients. The percentage of smokers, caucasians and primiparae per group was also similar. On the other hand, blood pressure parameters were elevated in the preeclamptic group. In addition, the preeclamptic group presented a significantly higher body mass index. The newborns of both groups presented similar APGAR scores and weights. Conclusion: In the presence of glibenclamide, there was an increase in the KCl-induced contractions only in vessels from the PE group, showing a possible involvement of these channels in the disorder.

Association between Doppler assessment and secondary cesarean delivery for intrapartum fetal compromise in small-for-gestational-age fetuses.

PURPOSE: To elucidate the association between arterial and venous Doppler ultrasound parameters and the risk of secondary cesarean delivery for intrapartum fetal compromise (IFC) and neonatal acidosis in small-for-gestational-age (SGA) fetuses. METHODS: This single-center, prospective, blinded, cohort study included singleton pregnancies with an estimated fetal weight (EFW) < 10th centile above 36 gestational weeks. Upon study inclusion, all women underwent Doppler ultrasound, including umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, fetal aortic isthmus (AoI) PI, umbilical vein blood flow (UVBF), and modified myocardial performance index (mod-MPI). Primary outcome was defined as secondary cesarean section due to IFC. RESULTS: In total, 87 SGA pregnancies were included, 16% of which required a cesarean section for IFC. Those fetuses revealed lower UVBF corrected for abdominal circumference (AC) (5.2 (4.5-6.3) vs 7.2 (5.5-8.3), p = 0.001). There was no difference when comparing AoI PI, UA PI, ACM PI, or mod-MPI. No association was found for neonatal acidosis. After multivariate logistic regression, UVBF/AC remained independently associated with cesarean section due to IFC (aOR 0.61 [0.37; 0.91], p = 0.03) and yielded an area under the curve (AUC) of 0.78 (95% CI, 0.67-0.89). A cut-off value set at the 50th centile of UVBF/AC reached a sensitivity of 86% and specificity of 58% for the occurrence of cesarean section due to IFC (OR 8.1; 95% CI, 1.7-37.8, p = 0.003). CONCLUSION: Low levels of umbilical vein blood flow (UVBF/AC) were associated with an increased risk among SGA fetuses to be delivered by cesarean section for IFC.

Fetal sex and the relative reactivity of human umbilical vein and arteries are key determinants in potential beneficial effects of phosphodiesterase inhibitors.

Intrauterine growth restriction (IUGR) is a common complication of pregnancy. We previously demonstrated that IUGR is associated with an impaired nitric oxide (NO)-induced relaxation in the human umbilical vein (HUV) of growth-restricted females compared to appropriate for gestational age (AGA) newborns. We found that phosphodiesterase (PDE) inhibition improved NO-induced relaxation in HUV, suggesting that PDEs could represent promising targets for therapeutic intervention. This study aimed to investigate the effects of PDE inhibition on human umbilical arteries (HUAs) compared to HUV. Umbilical vessels were collected in IUGR and AGA term newborns. NO-induced relaxation was studied using isolated vessel tension experiments in the presence or absence of the nonspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX). PDE1B, PDE1C, PDE3A, PDE4B, and PDE5A were investigated by Western blot. NO-induced vasodilation was similar between IUGR and AGA HUAs. In HUAs precontracted with serotonin, IBMX enhanced NO-induced relaxation only in IUGR females, whereas in HUV IBMX increased NO-induced relaxation in all groups except IUGR males. In umbilical vessels preconstricted with the thromboxane A2 analog U46619, IBMX improved NO-induced relaxation in all groups to a greater extent in HUV than HUAs. However, the PDE protein content was higher in HUAs than HUV in all study groups. Therefore, the effects of PDE inhibition depend on the presence of IUGR, fetal sex, vessel type, and vasoconstrictors implicated. Despite a higher PDE protein content, HUAs are less sensitive to IBMX than HUV, which could lead to adverse effects of PDE inhibition in vivo by impairment of the fetoplacental hemodynamics.NEW & NOTEWORTHY The effects of phosphodiesterase inhibition on the umbilical circulation depend on the presence of intrauterine growth restriction, the fetal sex, vessel type, and vasoconstrictors implicated. The human umbilical vascular tone regulation is complex and depends on the amount and activity of specific proteins but also probably on the subcellular organization mediating protein interactions. Therefore, therapeutic interventions using phosphodiesterase inhibitors to improve the placental-fetal circulation should consider fetal sex and both umbilical vein and artery reactivity.

European association of perinatal medicine (EAPM) position statement: Screening, diagnosis and management of congenital anomalies of the umbilical cord.

Congenital anomalies of the umbilical cord are associated with an increased risk of pregnancy and perinatal complications. Some anomalies of the cord have a higher prevalence than other fetal structural anomalies. The most common anomalies are the absence of an umbilical artery and velamentous insertion of the cord (with or without vasa previa). These anomalies, even when not associated with fetal structural defects, increase the risk of adverse perinatal outcome including, fetal growth restriction and stillbirth. In the absence of prenatal diagnosis, vasa previa is associated with the highest perinatal morbidity and mortality of all congenital anomalies of the umbilical cord. Most cases can be detected by ultrasound from the beginning of the second trimester and should be included in the routine mid-pregnancy ultrasound examination. Documentation should include cord insertion site, number of vessels in the cord, and if other pathologies have been detected. Pregnancies at increased risk of velamentous cord insertion should be screened for vasa previa using transvaginal ultrasound and colour Doppler imaging. If a velamentous cord insertion or isolated single umbilical artery is detected, individualised follow-up during pregnancy and tailored obstetric management are indicated.

Citral relaxes umbilical vessels of normotensive and preeclamptic parturients.

INTRODUCTION: Citral is a low-toxicity monoterpene that has a vasodilator effect on various smooth muscles, and The present study aimed to evaluate its vasorelaxant effect on umbilical vessels of normotensive parturients (NTP) and with preeclampsia parturients (PEP). METHOD: Segments of human umbilical artery (HUA) and vein (HUV) of NTP or PEP were mounted in a bath to record the force of contraction, under tension of 3.0 gf and contracted with the contracting agents: K+ (60 mM), 5 -HT (10 µM) and Ba2+ (1-30 mM). Next, the effect of citral (1-3000 µM) on these contractions and on basal tone was evaluated. RESULTS: In HUA and HUV, citral (1-1000 µM), in NTP condition, inhibited contractions evoked by K+ (IC50 of 413.5 and 271.3, respectively) and by 5-HT (IC50 of 164.8 and 574.3). In the PEP condition, in HUA and HUV, citral also inhibited the contractions evoked by K+ (IC50 of 363.3 and 218.3, respectively) and 5-HT (IC50 of 432.1 and 520.4). At a concentration of 1000 µM, citral completely or almost completely (>90 %) inhibited all contractions. At a concentration of 100-1000 µM, citral, in general, was already able to reduce the contraction induced by 1-3 mM Ba2+ in both AUH and VUH, under NTP and PEP conditions. DISCUSSION: Citral has been shown to be an effective HUA and HUV vasodilator in NTP and PEP. As its toxicity is low, it suggests that this substance can be considered a potential therapeutic agent.

Fetal external features and morphology of the umbilical cord of wild boars.

This study aimed to describe the gestational and morphological aspects of the fetuses and their respective umbilical cords from two pregnant wild boars (Sus scrofa). Morphological descriptions were provided for 23 fetuses and the gestational ages were estimated through fetal characteristics and formula application. The specimens were fixed in 10% formalin for subsequent macroscopic and microscopic examination. Histological characterization was performed using haematoxylin-eosin (H&E), Masson's trichrome (MT) and Verhöeff's staining techniques. The wild boar fetuses exhibited an estimated gestational age of 55 days (in the larger uterus) and 45 days (in the smaller uterus). They displayed well-developed features consistent with domestic pig fetuses, except for the presence of five pairs of mammae. Additionally, the umbilical cord consisted of two arteries, one vein, an allantoic duct, and a vitelline duct (the latter two identified only microscopically), located in the juxtafetal, intermediate and juxtaplacental portions. The arteries and veins were comprised of endothelium, smooth muscle and collagen fibres, with no elastic fibres observed in the vessel walls. The allantoic duct was lined with simple cuboidal epithelium, while the vitelline duct featured a simple squamous epithelium. In conclusion, the morphological characteristics observed in the examined structures align with the expected patterns for species of the Suidae family. Furthermore, these findings contribute substantially to the morphological characterization of the wild boar, yielding valuable insights into the fetal morphology and the structure of the umbilical cord.

Changes in metabolic acidosis following birth in intensive care unit neonates.

BACKGROUND: Little is known about how and why metabolic acidosis changes within the first six hours of life in intensive care unit neonates. OBJECTIVE: To determine changes in pH and base excess between paired umbilical cord arterial and neonatal arterial blood samples during the first 6 h of life, to identify factors associated with the direction and magnitude of change, and to examine morbidity and mortality in newborns with acidosis at birth or as neonates. STUDY DESIGN: Retrospective cohort study of all deliveries from a single institution between 2016-2020 with paired umbilical cord arterial and neonatal arterial samples obtained within 6 h of life meeting rigorous criteria to ensure sample integrity. The primary outcomes were the direction and magnitude of change of pH and base excess. Multiple factors were assessed for possible correlation with pH and base excess change. The secondary outcome was the association between a composite outcome of death or cerebral palsy and pathologic acidosis (pH ≤ 7.1) at birth or as a neonate. RESULTS: 102 patients met inclusion criteria. Newborn arterial gasses were obtained at a median of 1.5 h (74 % < 2 h). pH improved in 71 % of cases and worsened in 29 %, and base excess improved in 52 % and worsened in 48 %, with wide observed ranges in both parameters. The paired pH and base excess values were moderately (r = 0.38) and strongly (r = 0.63) positively correlated, respectively, but were not correlated with time since birth (r = 0.14). Low birth weight, prematurity or respiratory failure were associated with worsening or less improvement, while worse initial acidosis was associated with greater improvement. Death or survival with cerebral palsy was more common with pathologic acidosis in either cord or newborn sample as compared with those without acidosis (27.3 % vs 3.7 %, p = 0.003), and was more common in those with isolated neonatal acidosis as compared to those without acidosis (50 % vs 3.7 %, p = 0.016). CONCLUSIONS: Changes in pH and base excess occurred over a wide range between delivery and the first newborn blood gas in the first 6 h of life, and we identified several factors associated with direction of change. Metabolic acidosis at birth cannot reliably be inferred from neonatal arterial values. Neonatal acidosis, including acidosis following a normal pH and base excess at birth, was associated with morbidity and mortality.

Fetal hemodynamics and placental histopathology in Down syndrome.

OBJECTIVE: To evaluate the association between Doppler patterns in fetuses with Down syndrome (DS) and their placental histopathologic findings. METHODS: A retrospective cross-sectional study was performed by collecting data from medical records of singleton pregnancies between January 2014 and January 2022, whose fetuses had a confirmed diagnosis of DS either prenatally or postnatally. Placental histopathology, maternal characteristics, and prenatal ultrasound (biometric parameters and umbilical artery [UA] Doppler) were evaluated. RESULTS: Of 69 eligible pregnant women, 61 met the inclusion and exclusion criteria. In the sample, 15 fetuses had an estimated fetal weight < 10th percentile for gestational age (GA) and were considered small for gestational age (SGA). Thirty-eight fetuses had increased resistance on the UA Doppler. Histologic changes were detected in 100% of the placentas, the most common being delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism. More than 50% of the placentas showed alterations related to placental insufficiency. We did not observe a statistically significant association between UA Doppler examination and placental alterations. All placentas analyzed in the SGA subgroup showed findings compatible with placental insufficiency. CONCLUSION: We found no statistically significant association between placental histopathologic findings and UA Doppler abnormalities in fetuses with DS. The placental alterations identified were delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism.

Exploring the Topography of the Obturator Artery and Corona Mortis: a Detailed Analysis with Surgical Implications.

INTRODUCTION AND HYPOTHESIS: The obturator artery (ObA) is described as a branch of the anterior division of the internal iliac artery. It arises close to the origin of the umbilical artery, where it is crossed by the ureter. The main goal of the present study was to create an anatomical map of the ObA demonstrating the most frequent locations of the vessel's origin and course. METHODS: In May 2022, an evaluation of the findings from 75 consecutive patients who underwent computed tomography angiography studies of the abdomen and pelvis was performed. RESULTS: The presented results are based on a total of 138 arteries. Mostly, ObA originated from the anterior trunk of the internal iliac artery (79 out of 138; 57.2%). The median ObA diameter at its origin was found to be 3.34 mm (lower quartile [LQ] = 3.00; upper quartile [UQ] = 3.87). The median cross-sectional area of the ObA at its origin was found to be 6.31 mm2 (LQ = 5.43; UQ = 7.32). CONCLUSIONS: Our study developed a unique arterial anatomical map of the ObA, showcasing its origin and course. Moreover, we have provided more data for straightforward intraoperative identification of the corona mortis through simple anatomical landmarks, including the pubic symphysis. Interestingly, a statistically significant difference (p < 0.05) between the morphometric properties of the aberrant ObAs and the "normal" ObAs originating from the internal iliac artery was found. It is hoped that our study may aid in reducing the risk of serious hemorrhagic complications during various surgical procedures in the pelvic region.

Uterine contractile activity and neonatal outcome - A blind analysis of a randomized controlled trial cohort.

INTRODUCTION: Sufficient contractions are necessary for a successful delivery but each contraction temporarily constricts the oxygenated blood flow to the fetus. Individual fetal or placental characteristics determine how the fetus can withstand this temporary low oxygen saturation. However, only a few studies have examined the impact of uterine activity on neonatal outcome and even less attention has been paid to parturients' individual characteristics. Our objective was therefore to find out whether fetuses compromised by maternal or intrapartum risk factors are more vulnerable to excessive uterine activity. MATERIAL AND METHODS: Uterine contractile activity was assessed by intrauterine pressure catheters. Women (n = 625) with term singleton pregnancies and fetus in cephalic presentation were included in this secondary, blind analysis of a randomized controlled trial cohort. Intrauterine pressure as Montevideo units (MVU), contraction frequency/10 min and uterine baseline tone were calculated for 4 h prior to birth or the decision to perform cesarean section. Uterine activity in relation to umbilical artery pH linearly or ≤7.10 was used as the primary outcome. Need for operative delivery (either cesarean section or vacuum-assisted delivery) due to fetal distress was analyzed as a secondary outcome. In addition, belonging to vulnerable subgroups with, for example, chorioamnionitis, hypertensive or diabetic disorders, maternal smoking or neonatal birthweight <10th percentile were investigated as additional risk factors. RESULTS: A linear decline in umbilical artery pH was seen with increasing intrauterine pressure in all deliveries (p < 0.001). Among parturients with suspected chorioamnionitis, every increasing 10 MVUs increased the likelihood of umbilical artery pH ≤7.10 (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.02-1.34, p = 0.023). The need for operative delivery due to fetal distress was increased among all laboring women by every increasing 10 MVUs (OR 1.05, 95% CI 1.01-1.09, p = 0.015). This association with operative deliveries was further increased among parturients with hypertensive disorders (OR 1.23, 95% CI 1.05-1.43, p = 0.009) and among those with diabetic disorders (OR 1.13, 95% CI 1.04-1.28, p = 0.003). CONCLUSIONS: Increasing intrauterine pressure impairs umbilical artery pH especially among parturients with suspected chorioamnionitis. Fetuses in pregnancies affected by chorioamnionitis, hypertensive or diabetic disorders are more vulnerable to high intrauterine pressure.

Continuous Fetal Cardiac Monitoring during Fetoscopic Myelomeningocele Repair and Relationship to Spectral Doppler Changes.

INTRODUCTION: No evidence-based protocols exist for fetal cardiac monitoring during fetoscopic myelomeningocele (fMMC) repair and intraprocedural spectral Doppler data are limited. We determined the feasibility of continuous fetal echocardiography during fMMC repair and correlated Doppler changes with qualitative fetal cardiac function during each phase of fMMC repair. METHODS: Patients undergoing fMMC repair had continuous fetal echocardiography interpreted in real-time by pediatric cardiology. Fetal data included fetal heart rate (FHR), qualitative cardiac function, mitral and tricuspid valve inflow waveforms, and umbilical artery (UA), umbilical vein (UV), ductus arteriosus (DA), and ductus venosus (DV) Dopplers. RESULTS: UA abnormalities were noted in 14/25 patients, UV abnormalities were observed in 2 patients, and DV and DA abnormalities were each noted in 4 patients. Qualitative cardiac function was normal for all patients with the exception of one with isolated left ventricular dysfunction during myofascial flap creation, concurrent with an abnormal UA flow pattern. All abnormalities resolved by the first postoperative day. CONCLUSIONS: Continuous fetal echocardiography was feasible during all fMMC repairs. Spectral Doppler changes in the UA were common during fMMC procedures but qualitative cardiac dysfunction was rare. Abnormalities in the UV, DV, and DA Dopplers, FHR, and cardiac function were less common findings.

Hemodynamic changes and perinatal outcome associated with umbilical artery thrombosis: a retrospective study.

OBJECTIVE: Poor fetal and perinatal outcomes in fetuses associated with umbilical artery thrombosis (UAT), such as severe intrauterine growth restriction (IUGR) and intrauterine asphyxia have been reported by some case series. Its hemodynamic impact remains unclear. The aim of this study was to evaluate the hemodynamic changes and perinatal outcome in UAT fetuses with a relatively large sample. METHODS: We included singleton fetuses diagnosed with UAT and with at least one available Doppler evaluation before the end of pregnancy in our center from 2016 to 2023. Fetuses with structural abnormalities and with no follow-up results were excluded. Doppler waveforms from the Umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and uterine artery (UtA) were routinely evaluated according to ISUOG Practice Guidelines from diagnosis. The same sample of GA-matched normal fetuses with Doppler measurements during the same period were randomly selected as control group. RESULTS: Eighty-nine singleton fetuses with UAT with at least one Doppler evaluation before the end of pregnancy were identified, 13 fetuses with no follow-up results were excluded. After comprehensive prenatal counseling, 14 cases received urgent cesarean section, the remaining 55 cases received expectant management, the median day between GA at diagnosis and end of pregnancy was 13 (5-53) days (range, 2-159). 7 (7/76, 9.2%) cases occurred stillbirth, and the incidence of IUGR and Neonatal Intensive Care Unit (NICU) admission were 18.4% (14/76) and 13.2% (10/76) respectively. 49 fetuses (49/76, 64.5%) combined with Doppler abnormalities. UA abnormalities (35/76, 46.1%) and MCA abnormalities (34/76, 44.7%) were the most changes at presentation. Compared to control group, UA-EDV was significantly increased in UAT fetuses [21.84 (15.59-26.64) vs. 16.40 (12.43-20.70) cm/s, p < 0.001], UA-PI and UA-RI significantly decreased [0.68 (0.57-0.84) vs. 0.92 (0.79-1.11), p<0.001; 0.51 (0.44-0.59) vs. 0.62 (0.55-0.68), p < 0.001, respectively]. Both the MCA-PSV and MCA-EDV were significantly higher in UAT fetuses [54.60 (48.00-61.34) vs. 44.47 (29.66-57.60) cm/s, p < 0.001; 11.19 (7.84-17.60) vs. 8.22 (5.21-12.00) cm/s, p < 0.001, respectively], this led to a lower MCA-PI and MCA-RI. Meanwhile, DV-PIV was significantly higher in UAT fetuses [0.6 (0.47-0.87) vs. 0.45 (0.37-0.55), p < 0.001], CPR and UtA-PI were no significant difference between these two groups. Multivariate logistic regression analysis showed that DV-PIV was an independent risk factor for adverse pregnancy outcomes (OR 161.922, p<0.001), the area under the ROC curve (AUC) was 0.792 (95% CI 0.668-0.917; p < 0.001). CONCLUSION: Our data showed serious adverse pregnancy consequences are combined with UAT fetuses. Hemodynamic changes in UAT fetuses showed the remaining artery for compensation and brain perfusion derangement. With a comprehensive and standardized Doppler evaluation, progression of fetal deterioration may be detailed presented.

Expression and influence of KATP in umbilical artery smooth muscle cells of patients with hypertensive disorders of pregnancy.

The objective of this study is to investigate the expression and influence of adenosine triphosphate-sensitive potassium channel (KATP) in human umbilical arterial smooth muscle cells (HUASMCs) of patients with hypertensive disorders of pregnancy (HDP). Western blotting was used to detect the protein expression levels of KATP inwardly rectifying potassium channel (Kir)6.1 and sulphonylurea receptor (SUR)2B subunits in HUASMCs from patients with normal parturients (NP), gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE) and chronic hypertension with superimposed preeclampsia (CHSP), respectively. There was no significant difference in the protein expression of Kir6.1 subunit in NP group, GH group, CH group, PE group and CHSP group (P > 0.05). The protein expression of SUR2B subunit was gradually decreased in NP group, GH group, CH group, PE group and CHSP group, with statistically significant difference among the groups (P < 0.05). The altered expression level of KATP SUR2B subunit may be involved in the pathogenesis of HDP. The severity of HDP may be related to the degree of decrease of SUR2B subunit.

Diagnosis of single umbilical artery and risk of foetal congenital malformations by prenatal ultrasound: a retrospective study.

BACKGROUND: Single umbilical artery (SUA) is strongly associated with foetal structural abnormalities; however, the exact pattern of this association has not been described. We aimed to investigate the occurrence of malformations in singleton pregnancies with SUA in China and to study the association between the absent side of the umbilical artery and foetal malformations. METHODS: This was a retrospective study of singleton pregnancies for which routine first-trimester anatomical screening was performed at 11+ 0-13+ 6 gestational weeks and, if the pregnancy continued, a second-trimester scan was performed at 20+ 0-24+ 0 weeks. Data were extracted from records at the referral centre, the Obstetrics and Gynecology Hospital of Fudan University, between January 2011 and April 2019 (n = 47,894). Using logistic regression, the odds ratios (OR) with 95% confidence intervals (CIs) were calculated for malformations associated with SUA. RESULTS: The incidence of SUA in our study was 2.0% (970/47,894). Of all foetuses with SUA, 387 (39.9%) had structural malformations. The malformation type varied, with cardiovascular complications being the most common. A robust association was observed between SUA and oesophageal stenosis or atresia (OR: 25.33), followed by cardiovascular (OR: 9.98-24.02), scoliosis (OR: 18.62), genitourinary (OR: 2.45-15.66), and brain malformations (OR: 4.73-9.12). The absence of the left umbilical artery (n = 445, 45.9%) was consistent with that of the right umbilical artery (n = 431, 44.4%). Furthermore, a significantly higher rate of an absent right than the left umbilical artery (p<0.01) was observed in SUA with foetal abnormalities than in SUA with no malformations. CONCLUSIONS: Overall, we observed a higher risk of various specific malformations in foetuses with SUA, and a strong association between SUA and oesophageal stenosis or atresia. The absence of the right umbilical artery was most common in foetuses with SUA and structural malformations. This study provides a reference for ultrasonographers in conducting foetal structural screening for pregnant women with SUA.

Doppler ultrasound of umbilical and middle cerebral artery in third trimester small-for-gestational age fetuses to decide on timing of delivery for suspected fetal growth restriction: A cohort with nested RCT (DRIGITAT).

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

A new Doppler index, cerebro-placental-uterine ratio, and fetal cardiac parameters in early onset preeclampsia.

OBJECTIVE: Our aim was to investigate the significance of cerebro-placento-uterine ratio CPUR, a new Doppler index, and fetal cardiac parameters (Mod MPI, EFT) in early-onset preeclampsia (EOPE) and to examine whether these parameters are related to perinatal outcome. STUDY DESIGN: Forty participants diagnosed with EOPE (preeclampsia cases diagnosed before 34 weeks of gestation) and 40 healthy pregnant women were included in this study. Demographic data were recorded. Doppler parameters such as middle cerebral artery (MCA), umbilical artery (UA), and uterine artery (Ut-A), and left modified myocardial performance index (Mod-MPI) and epicardial fat thickness (EFT) were measured. Cerebroplacental ratio (CPR) was determined by dividing MCA pulsatility index (PI) by UA PI. CPUR was calculated as the ratio of CPR to mean UtA-PI (CPUR = CPR/UtA-PI). All parameters were compared between the EOPE and control groups. Correlation tests were used to examine the relationship between Doppler parameters and perinatal outcome. p values less than 0.05 were considered statistically significant. RESULTS: The pulsatility index of the middle cerebellar artery, CPUR and CPR values were statistically lower in the EOPE group than in the control group (p = 0.002; p = <0.001; p = <0.001; respectively). No statistical differences were found between groups for isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), ejection time (ET), left mod-MPI, EFT (p = 0.117; p = 0.093; p = 0.398; p = 0.882; p = 0.202, respectively). Umbilical artery Doppler pulsatility index (PI), mean uterine artery Doppler pulsatility index (PI), were higher in the EOPE group than in the control group (p = 0.006; and p = <0.001, respectively). The CPUR value for predicting EOPE was ≤1.3652 with 74. 4% sensitivity and 94.9% specificity. Positive correlations were found between CPUR, CPR, and some neonatal parameters. CONCLUSION: CPUR, a new index combining fetal and uterine Doppler indices, may add contribution to predict adverse perinatal outcome and EOPE.