The association of heat stress with fetal umbilical artery blood flow: a birth cohort study in Beijing, China

Intervillous thrombi (IVT) is one of the most common pathology findings during placental examination. The etiology and clinical significance of IVT are controversial. We previously collected placental data with fetal birth data and maternal pregnancy characteristics, and we examined IVT in the context of maternal, fetal, and placental pathology. A total of 3119 placentas with fetal birth and maternal pregnancy characteristics were examined, and IVT was found in 644 placentas (20.6%). IVT was statistically associated with advanced maternal age (P = .01) and clinical preeclampsia (P = .02). IVT was significantly associated with placental infarcts (P < .01), mural arterial hypertrophy (P = .02) as well as placental abruption (P < .01). In addition, IVT was significantly associated with velamentous cord insertion (P < .01). Regression analysis demonstrated the persistence of association between IVT placental infarct, in addition to 2 vessel cord (SUA) and fetal inflammatory response (FIR, acute funisitis/fetal vasculitis). Our data showed that IVT was independently associated with placental infarct, single umbilical artery, and fetal inflammatory response after regression analysis. The association of IVT with single umbilical artery and fetal inflammatory response points to fetal blood flow as potential pathogenic basis, providing new insight into pathogenic mechanisms and clinical significance.

IntroductionInterleukin-35 (IL-35), consisting of two subunits - Ebi3 and p35, is a pleiotropic anti-inflammatory cytokine implicated in fetal tolerance and pregnancy maintenance. Reduced IL-35 levels in abortion-prone mice and women with recurrent miscarriage suggest its deficiency contributes to pregnancy failure. In abortion-prone mice, IL-35 administration during mid-term gestation rescued pregnancy. However, it is unclear whether IL-35 administration before implantation (during the time of the first recognition of paternal antigens) can expand regulatory lymphocyte pools and restore maternal tolerance. Therefore, this study aimed to investigate the influence of intraperitoneal administration of recombinant IL-35 (rIL-35) and anti-Ebi3 antibody shortly after mating on successful pregnancy, fetal blood flow, and the profiles of several types of regulatory cells in a murine abortion-prone model.MethodsrIL-35 and anti-Ebi3 antibody were administered on 0 days post coitum (dpc). The embryos were imaged in PW Doppler mode on the 14th day of pregnancy. The frequencies of different subpopulations of Bregs (B10, MZ, T2-MZP, FO), Tregs, iTr35, γδ T, Th17 and NK cells were measured in uterine-draining lymph nodes, spleens and decidua using flow cytometry. The concentrations of Th1/Th2/Th17 cytokines in the serum were analyzed.ResultsThe main finding of our study is that we did not observe any differences in abortion rates between the groups. In the group that received the neutralizing antibody, a lower embryonic heart rate, lower circulatory competence of the fetal placenta, and elevated serum Th17/Th2 cytokine concentrations were observed. IL-35 administration increased the frequency of B10 and IL-35-producing B10 and regulatory T cells at the periphery and NKIL-35+ and CD19+IL-35+ but not Treg cells in the decidua.ConclusionsA single administration of IL-35 shortly after mating, does not have an anti-abortion effect. It exhibits a multifaceted effect on immune regulatory cells and IL-35 neutralization results in decreased embryonic heart rate and impaired placental–fetal circulation.

Introduction: Prenatal alcohol exposure (PAE) is a leading cause of birth defects and developmental impairments, resulting in a spectrum of disorders ranging from mild to severe, which are termed fetal alcohol spectrum disorders (FASD). Globally, there is a high prevalence of FASD, and currently, there is no known available cure. PAE most severely impacts the developing brain, causing long-term structural and functional impairments. Cerebral blood circulation plays a critical role in neuronal and overall brain development. Previous studies have shown that PAE leads to a decrease in fetal brain blood flow velocity via fetal cerebral artery dilation, but the specific targets underlying this effect remain largely unknown. Methods and Results: A previous study indicated that a mixture of cannabinoid blockers ablated alcohol-induced vasodilation, but the exact mechanism(s) involved have not been fully elucidated. Here, we investigated the concentration-dependent effects of alcohol on fetal cerebral arteries (anterior, middle, posterior, and basilar) in baboons (Papio sp.) using toxicologically relevant alcohol concentrations. We observed effects best described by polynomial fittings in both male and female fetuses, with low alcohol concentrations (5-30 mM) causing vasodilation. However, the alcohol concentrations that caused maximal dilation varied among cerebral arteries. Quantitative PCR analysis confirmed the presence of cannabinoid receptor 1 (CB1 receptor) but not cannabinoid receptor 2 (CB2 receptor) transcripts in fetal cerebral arteries. Probing of ex vivo pressurized cerebral arteries with a selective CB1 receptor antagonist (AM251) before alcohol exposure at the maximal vasodilating concentration resulted in decreased alcohol effect in the basilar arteries of female fetuses and in the middle cerebral arteries of male fetuses. In addition, liquid chromatography-mass spectrometry revealed no significant changes in endocannabinoid levels (anandamide and 2-arachydoniylglycerol). Our findings suggest that alcohol may activate CB1 receptors independently of endocannabinoid production to trigger vasodilation. Conclusions: In summary, alcohol induces fetal cerebral artery dilation via the CB1 receptor, with regional and sex-specific differences. Our work provides new insights into the role of the fetal cerebrovascular CB1 receptor in the effect of PAE on cerebral circulation.

Fetal growth restriction (FGR) secondary to placental insufficiency often leads to morbidity and mortality in the perinatal period. Fetal adaptations such as "brain sparing" blood flow redistribution offer some protection, but predicting whether a fetus in this state will survive is challenging. The goal of this research was to identify vascular responses predictive of stillbirth or hypoxia based on serial Doppler ultrasound measurement in a mouse model of FGR. We performed serial Doppler ultrasound observations of fetal blood flow redistribution in a murine model of FGR, where prolongation of pregnancy was induced pharmacologically with progesterone in 56 CD-1 mice. Observations were made at E18.5 (physiologic term), E19.5 (term +1), and E20.5 (term +2). Flow velocity waveforms were obtained from the middle cerebral artery (MCA), ductus arteriosus (DA), main pulmonary artery (MPA), ductus venosus (DV), umbilical artery (UA), and umbilical vein (UV). Following euthanasia, pimonidazole immunohistochemistry quantified tissue hypoxia. Among 56 pregnancies, the strongest predictor of stillbirth was low DA peak systolic velocity at E19.5 (<217 mm/s, P = 0.021, R2 = 0.52). Among survivors, cerebral hypoxia was predicted by elevated MCA peak systolic (>26.6 mm/s, P = 0.022, R2 = 0.59) and end-diastolic velocity (>10.1 mm/s, P = 0.043, R2 = 0.53, whereas high MPA flow (>0.73 mL/min, P = 0.029, R2 = 0.51) predicted hepatic hypoxia. Overall, fetuses with a weaker pulmonary blood flow redistribution response were found to have worse outcomes, despite cerebral vasodilation. This minimally invasive murine model offers valuable insights into this pathophysiology of FGR-related stillbirth and highlights the prognostic potential of assessing fetal brain flow and pulmonary perfusion in tandem during sonographic surveillance of high-risk pregnancies.NEW & NOTEWORTHY Fetal growth restriction, often caused by placental disease, is an important cause of fetal injury and stillbirth. Understanding how the fetus adapts under these conditions is key to predicting survival. Here we report physiological adaptations in a mouse of model of fetal growth restriction that predict the risk of stillbirth.

During pregnancy, the maternal hemostatic system undergoes significant changes to support placental angiogenesis, maintain fetal blood flow, and ensure safe delivery. This study investigates the dysregulation of hemostasis in placental insufficiency and explores potential markers for diagnosing and managing this gestational complication. Thromboelastography, coagulation and fibrinolysis functional assays, ELISA, and immunoblotting were employed to assess hemostasis dysregulation in placental dysfunction of two cohorts of pregnant women with placental dysfunction and healthy controls. Thromboelastographic analysis revealed no significant differences in clot lysis indices between the control and placental dysfunction groups, with values remaining within normal ranges, suggesting this method's limitations for assessing fibrinolysis in pregnancy. The placental dysfunction group demonstrated moderately increased fibrinogen levels and platelet sensitivity to ADP, indicating hemostasis reactiveness. Significantly lower D-dimer levels, decreased plasminogen activator inhibitor activity (total PAI-1 + PAI-2), and increased plasminogen activator activity, driven primarily by uPA in the placental dysfunction group, indicated abnormal fibrinolysis. Immunoblotting confirmed elevated uPA/uPA-PAI complexes and reduced tPA/tPA-PAI complexes, indicating that shutdown of tPA-mediated fibrinolysis and induction of uPA-driven vessel-wall-associated proteolysis are linked to placental dysfunction. Placental dysfunction involves fibrinolytic system dysregulation, marked by decreased PAI and tPA, uPA overproduction, and hypofibrinolysis, contributing to thrombotic risks, impaired placental flow, and complications like fetal growth retardation. PAI/PA ratio and D-dimer levels have diagnostic potential for placental-dysfunction-associated complications.

Placental hexokinase activity is related to fetal blood flow distribution in a cross-sectional study of healthy human pregnancies at term.

The effects of rIL-35 and anti-Ebi3 neutralizing antibody on regulatory lymphocytes and fetal blood flow in abortion-prone murine pregnancy model

ABSTRACTObjectiveTo characterize the fetoplacental response to acute maternal hyperoxygenation (AMH) in fetuses with suspected coarctation of the aorta (CoA) using fetal cardiac magnetic resonance imaging (MRI).MethodsPregnant women carrying a fetus with suspected CoA were recruited prospectively from a tertiary fetal cardiology center as part of the Fetal Imaging with Maternal Oxygen (FIMOx) study between February 2019 and April 2022. MRI included phase‐contrast flow measurements and oxygen‐sensitive T2* sequences to assess placental and fetal brain oxygenation. Results were analyzed on a groupwise basis, comparing true‐positive CoA cases (requiring surgical CoA repair ≤ 28 days after birth) to false positives.ResultsFetal MRI with AMH was performed in 20 pregnancies (mean ± SD gestational age, 33.0 ± 1.3 weeks), of which five had CoA and 15 were false positives. In both groups, AMH significantly increased the placental T2* signal but had no effect on cerebral T2*. Increased pulmonary blood flow with AMH was associated with reduced right–left shunting at the foramen ovale (r = −0.74, P < 0.001), but not with increased ascending aortic flow (r = 0.36, P = 0.177). Compared with baseline, AMH increased anterograde flow at the aortic isthmus from −2 (interquartile range (IQR), −57 to 10) mL/kg/min to 32 (IQR, −14 to 48) mL/kg/min (P < 0.001); however, this was associated with a reduction in superior vena cava flow (median, −29% (IQR, −41% to 0%); P < 0.001) and not with changes in ascending aortic flow. No differences in baseline or AMH phase‐contrast or T2* values usefully distinguished true‐ and false‐positive cases in this pilot study.ConclusionsAMH leads to a significant reduction in cerebral blood flow in fetuses with suspected CoA, which is the primary driver of changes in flow at the aortic isthmus. Future studies should consider the effects of maternal oxygen on the entirety of fetoplacental circulation, particularly for cases in which chronic maternal hyperoxygenation administration is being considered. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The application of Intuitionistic fuzzy total edge magic labelling to a graphical image at the 20th week of gestation provides insights into facilitates gender prediction as well as assessment of fetal blood flow on a second-trimester Doppler ultrasound screen. Ultrasounds screen the fetal heart rate during the 20th week of gestation using Doppler ultrasound for blood flow. A fetal heart rate above 2.5 beats per second suggests a female baby, while a rate less than 2.5 beats per second indicates a male baby. We convert the fetal heart blood flow into a graphical image and label it using intuitionistic fuzzy total edge magic labelling.

The role of umbilical vein blood flow assessment in the prediction of fetal growth velocity and adverse outcome: a prospective observational cohort study.

Background: Oligohydramnios, defined by reduced amniotic fluid volume, is a significant indicator of placental insufficiency and fetal compromise. Amniotic fluid plays a critical role in cushioning the fetus, supporting pulmonary development, and facilitating fetal movements. Doppler ultrasound of key fetal vessels, such as the umbilical artery (UA) and middle cerebral artery (MCA), provides valuable insights into fetal hemodynamics in compromised pregnancies. Evaluating these indices can help clinicians identify fetuses at risk and guide timely intervention. Objective: To compare the Doppler indices of the umbilical artery and middle cerebral artery between pregnant women diagnosed with oligohydramnios and those with normal amniotic fluid levels. Methods: This cross-sectional observational study was conducted at Jinnah Hospital Lahore and included 73 pregnant women between 18 and 40 years of age. Participants were divided into two groups: oligohydramnios (n=29) and normal amniotic fluid (n=44). Amniotic fluid levels were assessed using the amniotic fluid index (AFI) and single deepest pocket (SDP) methods. Doppler ultrasonography was used to measure peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI), resistance index (RI), and systolic/diastolic (S/D) ratios for both UA and MCA. Statistical analyses were performed using SPSS version 24, with a significance level set at p&lt;0.05. Results: The mean umbilical artery PSV was significantly lower in the oligohydramnios group (34.53 ± 17.60 cm/s) compared to the normal fluid group (52.85 ± 16.39 cm/s). Similarly, the MCA PSV was 36.54 ± 15.05 cm/s in oligohydramnios and 57.66 ± 19.71 cm/s in the normal group. MCA EDV was 10.62 ± 6.44 cm/s in oligohydramnios versus 21.39 ± 11.65 cm/s in controls. Although MCA PI was higher in oligohydramnios (1.40 ± 0.21) compared to normal (1.22 ± 0.35), this was not statistically significant (p=0.2668). No significant differences were observed in most RI and PI values. Conclusion: Oligohydramnios is associated with marked reductions in fetal blood flow velocities, especially in the umbilical and middle cerebral arteries, reflecting compromised fetal circulation. Doppler evaluation of these vessels offers a reliable, non-invasive method to monitor fetal well-being and anticipate adverse outcomes in high-risk pregnancies.

Background: Assessing fetal status and predicting perinatal outcomes in pregnant women with pre-eclampsia is a pressing issue in contemporary obstetrics. The management of pregnant women with pre-eclampsia and fetal growth retardation primarily relies on instrumental diagnostic methods; however, an additional biomarker capable of predicting the progression of this pregnancy complication and fetal deterioration is highly relevant. Aim: To determine the prognostic value of brain natriuretic peptide (NT-proBNP) for perinatal outcomes in patients with pre-eclampsia. Methods: A prospective study was conducted involving 110 pregnant women at 22–40 weeks of gestation to improve perinatal outcomes and reduce neonatal morbidity and mortality. The main group included 80 patients with confirmed pre-eclampsia of varying severity. Two subgroups were identified: 40 (50%) patients with fetal growth retardation and impaired umbilical artery blood flow, and 40 (50%) patients with pre-eclampsia without fetal growth retardation. The control group consisted of 30 women with uncomplicated pregnancies. The study was conducted from November 2022 to July 2024. Serum NT-proBNP levels were measured using electrochemiluminescence immunoassay. Uteroplacental and fetal blood flow was assessed upon the patient’s admission to the hospital using a Siemens ultrasound machine. Results: All patients completed the study. A statistically significant association was found between elevated NT-proBNP levels and fetal growth retardation with impaired umbilical artery blood flow (p 0.001). In the subgroup with fetal growth retardation and impaired umbilical artery blood flow, the NT-proBNP level was significantly higher compared with the subgroup without fetal growth retardation (227.25 vs. 79.50 pg/mL, respectively). Conclusion: Patients with pre-eclampsia of any severity who develop fetal growth retardation and impaired fetal circulation have NT-proBNP levels 2.8 times higher than those with pre-eclampsia without growth retardation. This supports the role of maternal cardiac maladaptation in pre-eclampsia. A threshold NT-proBNP value predictive of fetal growth retardation and impaired umbilical artery flow has been identified.

INTRODUCTION: The American College of Obstetricians and Gynecologists recommends moderate exercise during pregnancy; however, guidelines primarily target recreational exercisers and may not fully address the unique needs of athletes. As more women pursue athletic careers, there is a need for tailored recommendations that balance physiological changes during pregnancy with athletic performance. This study presents findings on the effects of pregnancy on physiology and athletic performance as well as the risks and benefits of exercise for pregnant athletes. METHODS: This review examines the existing literature on the relationship between exercise, maternal health, and athletic performance. A total of 22 studies involving 4,163 participants were analyzed. RESULTS: Regular exercise during pregnancy is associated with reduced risk of gestational diabetes and hypertensive disorders, and improved cardiovascular fitness. Exercise enhances fetal vascular function, potentially reducing the risk of a macrosomic infant. For professional athletes, individualized exercise regimens are essential, as high-intensity activities can affect fetal heart rate and blood flow. Training at more than 90% of maximal heart rate may lead to fetal growth retardation. Strength training in elite athletes, although beneficial, must be approached with caution due to potential risks such as elevated intra-abdominal pressure and reduced fetal blood flow. Endurance athletes may maintain fitness during pregnancy without adverse outcomes, whereas those engaging in high-altitude or contact sports require adjustments to training protocols. CONCLUSIONS/IMPLICATIONS: Exercise during pregnancy benefits both maternal and fetal health; however, elite athletes need individualized guidelines to safely continue training. Further research is required to establish specific recommendations that support the health and career longevity of pregnant athletes.

Reduced placental microvascular perfusion is the most important cause of fetal growth restriction (FGR), yet there are currently no effective tools available for assessing placental microcirculation. Ultrasound microangiography is an emerging technology capable of imaging vessels at the micron level. Currently, there is no research on the application of ultrasound microangiography technology for assessing placental microcirculation. This study innovatively explores the feasibility and practicality of using this new technology to evaluate microvascular changes in the placenta in cases of FGR. Ultrasound microangiography was used to image the microvascular structure and quantitatively analyze microvascular density in 10 FGR placentas and 10 normal placentas from Sprague-Dawley rats. Doppler ultrasound measurements were performed on the uterine arteries, the fetal umbilical arteries, and the middle cerebral arteries of pregnant rats. Placental area and thickness were measured, and hematoxylin and eosin (H&E)-stained placental sections were analyzed to assess the uterine spiral artery wall-to-lumen ratio. Histological determination of placental microvascular density served as the standard for validation. In FGR cases, the remodeling of the uterine spiral arteries was obstructed, with the placenta exhibiting thinning and increased area. Both placental and fetal blood flow dynamics were altered. Using ultrasound microangiography, real-time dynamic imaging of blood flow from the large placental vessels to the micro-branching vessels was achieved. The shapes of the microvessels were rapidly visualized and reached peak visibility, displaying microvessels with slower flow rates. The boundaries between the microvessels and the placental background were sharply defined, and the placental vasculature formed an orderly, detailed vascular tree. Quantitative analysis of microvascular density in FGR placentas revealed a significant reduction compared with the control group (P < 0.01), a finding further confirmed by immunohistochemistry. Ultrasound microangiography demonstrates significant advantages in visualizing and quantifying the microvascular features of FGR placentas, enhancing the diagnostic capability for placental vascular diseases in FGR. This new technology provides a novel approach to the prenatal diagnosis of FGR.

Preeclampsia (PE) induces adverse cardiovascular outcomes for both mother and offspring. We established a novel leptin-induced mouse model of PE that induces hypertension, endothelial dysfunction, and fetal growth restriction, which are collectively ablated by endothelial cell mineralocorticoid receptor (MR) deletion. However, literature lacks preclinical evidence to use MR antagonism for PE patients. We hypothesize eplerenone will improve blood pressure, vascular function and fetal outcomes in leptin-infused pregnant mice. We infused timed-pregnant Balb/c mice with saline (sham) or leptin (LEP, 0.9mg/kg/day) via s.c. osmotic minipump and administered vehicle (VEH) or eplerenone (EPL, 200mg/kg/day) from gestation day (GD)11-18 (n=9-15). We measured mean arterial blood pressure (BP) via radiotelemetry, vascular function in 2 nd order mesenteric arteries by wire myography, and pup/placental weights on GD18. We measured uterine artery resistance index (UARI) via ultrasound measurement of peak systolic and end diastolic velocities. Pairwise comparisons were by student’s t-test and myography analyzed by 2-Way ANOVA w/RM, mean±SEM (*p&lt;0.05, **p&lt;0.01). EPL ablated LEP-induced increases in BP (98±4 LEP-EPL vs 113±3LEP-VEH mmHg,*) and prevented LEP from decreasing vascular relaxation responses to acetylcholine, a measure of endothelial function (concentration-response curve, p&gt;0.05 vs SHAM-VEH). LEP decreased placental efficiency and pup weight, however, so also did EPL treatment as an independent variable (pup/placenta ratio: 8.1±0.1 SHAM-VEH, 7.4±0.1 LEP-VEH, 8.1±0.2 SHAM-EPL, 6.9±0.1 LEP-EPL, *for both effect of LEP and EPL), (pup weight: 0.73±0.007g SHAM-VEH, 0.71±0.010 LEP-VEH, 0.71±0.009 SHAM-EPL, 0.66±0.007 LEP-EPL, *for both effect of LEP and EPL). LEP increases plasma endothelin-1 measured via ELISA (2.132±0.389 LEP-VEH vs. 1.359±0.109 SHAM-VEH) and UARI data indicates that EPL treatment increases UARI in leptin-infused pregnant mice (0.52 LEP-VEH vs 0.60 LEP-EPL PSV/EDV). Interestingly, mRNA expression of NADPH oxidase (NOX) 1 and 2 in mouse placenta were significantly increased in the EPL treated mice compared to VEH (∆∆Ct to 18s: 1.2±0.28 SHAM-VEH, 1.1±0.317 LEP-VEH, 1.9±0.3462 SHAM-EPL, 2.9±0.706 LEP-EPL, **, NOX1; 1.1±0.306 SHAM-VEH, 1.1±0.253 LEP-VEH, 1.7±0.369 SHAM-EPL, 3.0±0.684 LEP-EPL, **, NOX2; both for effect of EPL). Collectively, these data suggest that EPL may ablate LEP-induced hypertension and endothelial dysfunction in PE mice. However, EPL did not improve fetal growth in LEP-induced PE. EPL increases NOX1/2, indicating an increase for ROS and may fail to improve placental function induced by leptin, potentiating an increase in UARI and potentially lower fetal blood flow. AHA 24PRE1192508, NIH 1R01HL169576 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Present study included 28 healthy bitches which, based on modes of whelping, were divided into four groups viz., Group I (Vaginal whelping/VW), Group II (elective caesarean section/CS), Group III (emergency CS) and Group IV (induction of whelping). Doppler evaluations were conducted within one hour before whelping to assess blood flow measurements in the uteroplacental artery (UPA), umbilical artery (UMA), and fetal abdominal aorta (FAA) using pulsatility (PI) and resistance indices (RI). The mean PI and RI of UPA were 1.10 ± 0.06, 1.30 ± 0.09, 1.07 ± 0.06, and 1.07 ± 0.10, and 0.62 ± 0.02, 0.71 ± 0.02, 0.64 ± 0.02 and 0.66 ± 0.04 respectively, in Groups I, II, III and IV. The mean PI and RI of UMA were 1.26 ± 0.05, 1.39 ± 0.07, 1.23 ± 0.07 and 1.21± 0.11, and 0.67 ± 0.01, 0.73 ± 0.02, 0.70 ± 0.03 and 0.67 ± 0.03 respectively, in the aforesaid groups. The mean PI and RI of FAA were 1.36 ± 0.11, 1.55 ± 0.10, 1.55 ± 0.07 and 1.40 ± 0.16, and 0.73 ± 0.02, 0.72 ± 0.02, 0.75 ± 0.01 and 0.71 ± 0.03, respectively in the aforesaid groups. No significant difference (p&gt;0.05) could be noticed in the mean PI and RI of different vessels between the groups on the day of parturition. Increased Doppler indices, especially in the UPA, close to whelping may result from reduced diastolic blood flow to the uterus due to uterine contractions.

SummaryObjectiveThe aim was to evaluate the association between fetal vascular malperfusion (FVM) and the umbilical cord characteristics in stillbirth. FVM is a category of placental lesions consistent with restriction/interruption of fetal blood flow, frequently associated with a “cord accident”. In some stillbirths, gross umbilical cord abnormalities unravel at birth, helping to elucidate the cause of death; however, other cases do not show any structural alterations and therefore these cases do not have an obvious cause of death.MethodsRetrospective histopathological evaluation of singleton antepartum stillbirths affected by of FVM. Clinical and histopathological findings were compared among cases with or without gross umbilical cord abnormalities.ResultsOne hundred and three cases were evaluated. Forty-eight cases (48/103; 46.6%) of stillbirth with FVM showed gross umbilical cord abnormalities, whereas 55/103 cases (53.4%) did not show any gross anomalies. Clinical risk factors for stillbirth were equally distributed between cases. Notably, the main histological lesion observed in cases without gross umbilical cord abnormalities was fatal thrombosis of the fetal vessels along the cord-placental vascular tree. This finding implies that the absence of macroscopic cord anomalies is not a sufficient criterion to exclude reduction/interruption of fetal blood flow and cord accidents as a potential cause of stillbirth.ConclusionKnowing the cause of fetal death is paramount both for bereaved parents and clinicians, helping in stillbirth acceptance and future prevention strategies. Our findings show the occurrence of FVM in cases without macroscopic umbilical cord anomalies. Therefore, an in-depth placental histopathological examination is mandatory to unravel signs of fetal blood flow obstruction in cases in which umbilical cord looks grossly normal. This knowledge helps parents, and health care providers in the real identification of the pathogenesis of fetal death, as the first step for personalized future actions of stillbirth prevention.

Aim - to study ultrasound signs of perinatal complications in newborns born to mothers who suffered from COVID-19 during pregnancy. Materials and methods. All pregnant women (140 women with a positive test for COVID-19 gave birth, from whom 142 children were born (2 dichorionic, diamniotic twins) of the main group and 103 children (3 dichorionic, diamniotic twins) of the control group) underwent a full ultrasound of the fetus with fetal echocardiography, as well as an assessment of the state of the uteroplacental and fetal blood flow in different vascular pools in the period of 11-39 weeks of pregnancy to determine the presence of signs of intrauterine infection, detection of accompanying pathology, structural changes in the placenta, the amount of amniotic fluid and the degree of hemodynamic disturbances in the fetoplacental system. Results. 20 (14%) newborns required treatment in the intensive care unit and intensive care unit after delivery. Significant changes were registered in the structure of the placenta, vessels of the subchorionic space, which was accompanied by an increase in the amount of amniotic fluid (17.1% versus 8.0% in the control group). There was an increase in the percentage of fetuses with distress (18.6% vs. 8.0%) and fetal growth retardation syndrome (11.4% vs. 3.0%) compared to the control group. It should be noted that the risk of premature birth increased in the presence of fever, hypoxemia, severe respiratory disorders and increased amounts of amniotic fluid. In the main group of newborns, in comparison with the control group, respiratory distress syndrome, pneumonia, damage to the cardiovascular system were more often noted. At the same time, the percentage of congenital malformations practically did not differ in the main and control groups, on the basis of which it can be concluded that the SARS-CoV-2 virus does not cause the formation of congenital malformations associated with this disease. Thus, detection of ventriculodilatation, pyeloectasia , and expansion of intestinal loops were the basis for urgent ultrasound of newborns. Features detected during fetal echocardiography in fetuses from mothers of the main group, namely: dilatation of the right parts of the fetal heart, thickening of the walls of the ventricles due to the endocardium with an increase in its echogenicity, disturbances of the heart rhythm and conduction, hydropericardium indicated the probability of the presence of myocarditis. Conclusions. A complex non-invasive ultrasound examination of fetuses and newborns, when mothers are infected with COVID-19, reveals manifestations of damage to the cardiovascular, digestive, urinary systems and brain structures. The most threatening condition is myocarditis of newborns. The study was conducted in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent was obtained from the patients for conducting the study. The authors declare no conflict of interest.

Cerebral hemodynamic adaptation in fetal growth restriction (FGR) is primarily assessed using middle cerebral artery (MCA) Doppler and cerebroplacental (CPR) or umbilicocerebral ratio (UCR). The superior vena cava (SVC) blood flow may provide additional hemodynamic insights. Our objective was to evaluate fetal SVC blood flow velocities, pulsatility index for vein (PIV), volume blood flow (QSVC), and volume blood flow (Q)-based indices of fetal brain sparing in small-for-gestational-age (SGA) and FGR fetuses in the third trimester of pregnancy and compare with appropriately grown (AGA) fetuses. This was a prospective cohort study of 40 non-anomalous, singleton fetuses during 32 + 0 to 36 + 6 gestational weeks. Fetuses with abdominal circumference or estimated fetal weight below the 10th percentile were classified into SGA and FGR groups based on Delphi criteria. Doppler velocimetry of the umbilical artery (UA), umbilical vein (UV), fetal MCA and SVC was performed. UV and SVC diameters were measured, and their volume blood flows, i.e. QUV and QSVC were calculated. Both pulsatility index (PI)-based and Q-based indices of fetal brain sparing were calculated and compared to previously reported reference ranges for AGA fetuses using z-scores. In our study population, z-scores of SVC velocities (except the end-diastolic A-wave velocity) and PIV were significantly lower than the gestational age-specific mean values for AGA fetuses (p-values 0.005 to 0.018). Similarly, z-scores of SVC diameter (p < 0.001), QSVC normalized to fetal weight (QSVCw) (p < 0.001), blood flow volume-based QCPR (p < 0.001) were higher and QUCR (p < 0.001) was lower. However, z-scores of PI-based CPR (p = 0.195), UCR (p = 0.195), and the end-diastolic (A wave) velocity (p = 0.177) were not significantly different compared to AGA fetuses. Subgroup analysis demonstrated that the FGR fetuses (n = 21) had increased SVC diameter (p < 0.001), QSVCw (p < 0.001), QCPR (p < 0.001), UCR (p < 0.001), and decreased CPR (p < 0.001), QUCR (p < 0.001) and SVC PIV (p = 0.030), but no significant change in velocities was observed compared to AGA fetuses (n = 98) of similar gestational age. The SGA fetuses (n = 19) had decreased SVC S velocity (p = 0.013), D velocity (p = 0.005), TAMxV (p = 0.030), PIV (p = 0.005), QUCR (p = 0.014), and increased SVC diameter (p = 0.026), QSVCw (p = 0.034) and QCPR (p = 0.014) in comparison to AGA fetuses. When compared to SGA fetuses, the FGR fetuses had significantly lower QUVw (60.5 ± 19.7 vs. 80.1 ± 20.2 ml/min/kg, p = 0.004), QUCR (0.79 ± 0.45 vs. 1.34 ± 0.52 p < 0.001) and birthweight (2181 ± 577 vs. 2848 ± 330 g, p < 0.001) but higher QSVCw (91.82 ± 39.56 vs. 65.53 ± 17.79 ml/min/kg, p = 0.039) and QCPR (1.63 ± 0.74 vs. 0.90 ± 0.45, p < 0.001). In conclusion, third-trimester fetuses < 10th percentile had significantly increased SVC diameter, resulting in increased QSVCw in SGA and FGR despite reduced or unchanged TAMxV. Significantly altered QCPR and QUCR confirmed circulatory redistribution with increased brain and upper body venous return both in FGR and SGA fetuses. However, as the magnitude of increase in QSVCw and QCPR was significantly larger in FGR compared to SGA fetuses, it could be potentially used as a quantifiable marker to differentiate FGR from SGA. The role of SVC Doppler in refining the diagnosis of late FGR should be further investigated.