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1.
Placenta ; 152: 65-71, 2024 Jul.
Article En | MEDLINE | ID: mdl-38810530

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.


Acyclic Monoterpenes , Monoterpenes , Pre-Eclampsia , Umbilical Arteries , Vasodilator Agents , Humans , Female , Pregnancy , Pre-Eclampsia/physiopathology , Acyclic Monoterpenes/pharmacology , Monoterpenes/pharmacology , Umbilical Arteries/drug effects , Adult , Vasodilator Agents/pharmacology , Umbilical Veins/drug effects , Vasodilation/drug effects
2.
J Appl Physiol (1985) ; 136(6): 1526-1545, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38695358

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.


Fetal Growth Retardation , Nitric Oxide , Phosphodiesterase Inhibitors , Umbilical Arteries , Umbilical Veins , Vasodilation , Humans , Female , Umbilical Arteries/drug effects , Male , Vasodilation/drug effects , Vasodilation/physiology , Umbilical Veins/drug effects , Phosphodiesterase Inhibitors/pharmacology , Fetal Growth Retardation/drug therapy , Fetal Growth Retardation/physiopathology , Nitric Oxide/metabolism , Pregnancy , Infant, Newborn , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , 1-Methyl-3-isobutylxanthine/pharmacology , Sex Factors , Phosphoric Diester Hydrolases/metabolism
3.
Eur J Obstet Gynecol Reprod Biol ; 298: 61-65, 2024 Jul.
Article En | MEDLINE | ID: mdl-38728843

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.


Ultrasonography, Prenatal , Umbilical Cord , Humans , Female , Umbilical Cord/abnormalities , Umbilical Cord/diagnostic imaging , Pregnancy , Vasa Previa/diagnosis , Vasa Previa/diagnostic imaging , Vasa Previa/therapy , Umbilical Arteries/diagnostic imaging , Umbilical Arteries/abnormalities , Europe
4.
Am J Reprod Immunol ; 91(5): e13858, 2024 May.
Article En | MEDLINE | ID: mdl-38762781

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.


Biomarkers , Fetal Growth Retardation , Syndecan-1 , Humans , Syndecan-1/blood , Fetal Growth Retardation/blood , Female , Pregnancy , Adult , Biomarkers/blood , Gestational Age , Infant, Newborn , Umbilical Arteries/diagnostic imaging , Placenta/metabolism , Endothelium, Vascular/physiopathology
5.
Article En | MEDLINE | ID: mdl-38765503

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.


Glyburide , Pre-Eclampsia , Umbilical Arteries , Humans , Female , Pregnancy , Pre-Eclampsia/physiopathology , Umbilical Arteries/physiopathology , Adult , Glyburide/pharmacology , Vasoconstriction/drug effects , Young Adult , KATP Channels/metabolism , Potassium Chloride/pharmacology
6.
Acta Obstet Gynecol Scand ; 103(7): 1396-1407, 2024 Jul.
Article En | MEDLINE | ID: mdl-38567650

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.


Uterine Contraction , Humans , Female , Pregnancy , Uterine Contraction/physiology , Infant, Newborn , Adult , Pregnancy Outcome , Cesarean Section/statistics & numerical data , Fetal Distress/physiopathology , Cohort Studies , Risk Factors , Umbilical Arteries
7.
Int Urogynecol J ; 35(5): 1051-1060, 2024 May.
Article En | MEDLINE | ID: mdl-38635039

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.


Computed Tomography Angiography , Iliac Artery , Humans , Female , Iliac Artery/anatomy & histology , Iliac Artery/diagnostic imaging , Middle Aged , Aged , Adult , Pelvis/blood supply , Pelvis/diagnostic imaging , Pelvis/anatomy & histology , Umbilical Arteries/diagnostic imaging , Umbilical Arteries/anatomy & histology
8.
Eur J Obstet Gynecol Reprod Biol ; 297: 161-168, 2024 Jun.
Article En | MEDLINE | ID: mdl-38657521

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.


Acidosis , Intensive Care Units, Neonatal , Humans , Infant, Newborn , Acidosis/blood , Acidosis/epidemiology , Retrospective Studies , Female , Intensive Care Units, Neonatal/statistics & numerical data , Male , Hydrogen-Ion Concentration , Fetal Blood/chemistry , Umbilical Arteries
9.
Anat Histol Embryol ; 53(3): e13041, 2024 May.
Article En | MEDLINE | ID: mdl-38629204

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.


Fetus , Umbilical Cord , Pregnancy , Female , Animals , Swine , Umbilical Cord/anatomy & histology , Allantois/anatomy & histology , Gestational Age , Sus scrofa , Umbilical Arteries
10.
J Sci Med Sport ; 27(7): 480-485, 2024 Jul.
Article En | MEDLINE | ID: mdl-38508889

OBJECTIVES: Antenatal exercise is associated with placental morphological alterations, however research in this area is limited. Given the emphasis on the beneficial effects of antenatal exercise, it is important to understand its effect on placental function and the relationship to foetal development. The aim of this study was to investigate the association between physical activity, sitting time, and placental outcomes measured during gestation. DESIGN: Prospective cohort study. METHODS: Pregnant women in the Queensland Family Cohort study self-reported physical activity at 24 and 36 weeks of gestation (n = 203) and were categorised into physical activity volume groups of nil-low (0-<500 metabolic equivalent of task·minutes/week), moderate (500-<1000 metabolic equivalent of task·minutes/week), or high-volume activity (≥1000 metabolic equivalent of task·minutes/week). Participants reported average daily sitting time, whereby excessive sitting time was considered as ≥8h/day. Placental stiffness, thickness, and uteroplacental blood flow resistance were measured by ultrasound imaging at each timepoint. RESULTS: Physical activity volume was not associated with changes to placental morphometrics or uteroplacental blood flow resistance at 24 or 36 weeks of gestation. Excessive sitting time at 36 weeks was associated with greater placental stiffness (p = 0.046), and a lower umbilical artery pulsatility index (p = 0.001). CONCLUSIONS: Placental tissue stiffness and umbilical artery resistance were altered in late gestation with higher maternal sitting time but not with physical activity volume. Overall, excessive sitting time may be a risk for suboptimal placental function and could be an important focus for antenatal care.


Exercise , Placenta , Sitting Position , Humans , Female , Pregnancy , Exercise/physiology , Placenta/anatomy & histology , Placenta/blood supply , Placenta/physiology , Adult , Prospective Studies , Queensland , Umbilical Arteries/diagnostic imaging , Umbilical Arteries/physiology , Young Adult , Sedentary Behavior
11.
J Clin Ultrasound ; 52(5): 558-565, 2024 Jun.
Article En | MEDLINE | ID: mdl-38538067

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.


Middle Cerebral Artery , Placenta , Pre-Eclampsia , Ultrasonography, Doppler , Ultrasonography, Prenatal , Umbilical Arteries , Uterine Artery , Humans , Female , Pregnancy , Ultrasonography, Prenatal/methods , Adult , Pre-Eclampsia/physiopathology , Pre-Eclampsia/diagnostic imaging , Uterine Artery/diagnostic imaging , Uterine Artery/physiopathology , Ultrasonography, Doppler/methods , Umbilical Arteries/diagnostic imaging , Umbilical Arteries/physiopathology , Middle Cerebral Artery/diagnostic imaging , Middle Cerebral Artery/physiopathology , Placenta/diagnostic imaging , Placenta/blood supply , Fetal Heart/diagnostic imaging , Fetal Heart/physiopathology , Uterus/blood supply , Uterus/diagnostic imaging , Pulsatile Flow/physiology
12.
Am J Obstet Gynecol ; 231(1): 130.e1-130.e10, 2024 Jul.
Article En | MEDLINE | ID: mdl-38527602

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


Fetal Growth Retardation , Pulsatile Flow , Ultrasonography, Prenatal , Umbilical Arteries , Humans , Female , Umbilical Arteries/diagnostic imaging , Umbilical Arteries/physiopathology , Pregnancy , Fetal Growth Retardation/physiopathology , Fetal Growth Retardation/diagnostic imaging , Retrospective Studies , Adult , Vascular Resistance , Infant, Newborn , Ultrasonography, Doppler , Pregnancy Outcome , Gestational Age , Cohort Studies
13.
BJOG ; 131(8): 1042-1053, 2024 Jul.
Article En | MEDLINE | ID: mdl-38498267

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.


Fetal Growth Retardation , Infant, Small for Gestational Age , Middle Cerebral Artery , Pregnancy Trimester, Third , Ultrasonography, Doppler , Ultrasonography, Prenatal , Umbilical Arteries , Humans , Female , Pregnancy , Fetal Growth Retardation/diagnostic imaging , Umbilical Arteries/diagnostic imaging , Middle Cerebral Artery/diagnostic imaging , Adult , Infant, Newborn , Delivery, Obstetric/methods , Pregnancy Outcome , Cohort Studies , Gestational Age
14.
Sci Rep ; 14(1): 7517, 2024 03 29.
Article En | MEDLINE | ID: mdl-38553483

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.


Hypertension, Pregnancy-Induced , Pre-Eclampsia , Pregnancy , Female , Humans , Umbilical Arteries/metabolism , Pre-Eclampsia/genetics , Sulfonylurea Receptors/metabolism , Myocytes, Smooth Muscle/metabolism , Adenosine Triphosphate/metabolism , KATP Channels/genetics , KATP Channels/metabolism
15.
Orphanet J Rare Dis ; 19(1): 100, 2024 Mar 05.
Article En | MEDLINE | ID: mdl-38444029

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.


Thrombosis , Umbilical Arteries , Infant, Newborn , Pregnancy , Humans , Female , Umbilical Arteries/diagnostic imaging , Retrospective Studies , Cesarean Section , Fetus , Fetal Growth Retardation
16.
BMC Pregnancy Childbirth ; 24(1): 193, 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38475732

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.


Esophageal Stenosis , Single Umbilical Artery , Pregnancy , Female , Humans , Single Umbilical Artery/epidemiology , Retrospective Studies , Ultrasonography, Prenatal , Umbilical Arteries/diagnostic imaging , Fetus/abnormalities
17.
J Perinat Med ; 52(4): 416-422, 2024 May 27.
Article En | MEDLINE | ID: mdl-38407148

OBJECTIVES: To investigate the clinical outcomes and Doppler patterns changes in monochorionic diamniotic (MCDA) twins with selective fetal growth restriction (sFGR). METHODS: We retrospectively analyzed 362 sFGR cases from January 2010 to May 2016 at a single tertiary referral center. The Doppler waveforms of umbilical artery end-diastolic flow were collected, and all neonates were subjected to an early neonatal brain scan. RESULTS: A total of 66/100 (66 %) type I cases were stable, whereas 25/100 (25 %) cases changed to type II and 9/100 (9 %) changed to sFGR complicated twin-twin transfusion syndrome (TTTS). A total of 48.9 % (22/45) sFGR cases were complicated with polyhydramnios and 30.4 % (7/23) sFGR cases were complicated with oligohydramnios, both of which were progressed to sFGR with TTTS. Mild cerebral injury was significantly associated with Doppler flow abnormalities, earlier gestational age at delivery and type of sFGR diagnosis. Severe cerebral injury was significantly associated with gestational age at delivery (31.6 vs. 34.1, p=0.002) and larger birthweight discordance (43.9 vs. 29.3 %, p=0.011). CONCLUSIONS: Doppler patterns in sFGR can gradually change, with important consequences with regard to management and outcomes. Along with abnormal Doppler findings, earlier occurrence of sFGR and delivery are associated with subsequent neonatal cerebral injury.


Fetal Growth Retardation , Ultrasonography, Doppler , Ultrasonography, Prenatal , Humans , Fetal Growth Retardation/diagnostic imaging , Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/physiopathology , Female , Pregnancy , Retrospective Studies , Ultrasonography, Prenatal/methods , Infant, Newborn , Ultrasonography, Doppler/methods , Umbilical Arteries/diagnostic imaging , Fetofetal Transfusion/diagnostic imaging , Fetofetal Transfusion/diagnosis , Fetofetal Transfusion/physiopathology , Twins, Monozygotic , Adult , Pregnancy, Twin , Pregnancy Outcome/epidemiology , Gestational Age
18.
Eur J Pediatr ; 183(5): 2163-2172, 2024 May.
Article En | MEDLINE | ID: mdl-38367065

Low Apgar scores and low umbilical arterial (UA) blood pH are considered indicators of adverse perinatal events. This study investigated trends of these perinatal health indicators in Germany. Perinatal data on 10,696,831 in-hospital live births from 2008 to 2022 were obtained from quality assurance institutes. Joinpoint regression analysis was used to quantify trends of low Apgar score and UA pH. Additional analyses stratified by mode of delivery were performed on term singletons with cephalic presentation. Robustness against unmeasured confounding was analyzed using the E-value sensitivity analysis. The overall rates of 5-min Apgar scores < 7 and UA pH < 7.10 in liveborn infants were 1.17% and 1.98%, respectively. For low Apgar scores, joinpoint analysis revealed an increase from 2008 to 2011 (annual percent change (APC) 5.19; 95% CI 3.66-9.00) followed by a slower increase from 2011 to 2019 (APC 2.56; 95% CI 2.00-3.03) and a stabilization from 2019 onwards (APC - 0.64; 95% CI - 3.60 to 0.62). The rate of UA blood pH < 7.10 increased significantly between 2011 and 2017 (APC 5.90; 95% CI 5.15-7.42). For term singletons in cephalic presentation, the risk amplification of low Apgar scores was highest after instrumental delivery (risk ratio 1.623, 95% CI 1.509-1.745), whereas those born spontaneous had the highest increase in pH < 7.10 (risk ratio 1.648, 95% CI 1.615-1.682).          Conclusion: Rates of low 5-min Apgar scores and UA pH in liveborn infants increased from 2008 to 2022 in Germany. What is Known: • Low Apgar scores at 5 min after birth and umbilical arterial blood pH are associated with adverse perinatal outcomes. • Prospective collection of Apgar scores and arterial blood pH data allows for nationwide quality assurance. What is New: • The rates of liveborn infants with 5-min Apgar scores < 7 rose from 0.97 to 1.30% and that of umbilical arterial blood pH < 7.10 from 1.55 to 2.30% between 2008-2010 and 2020-2022. • In spontaneously born term singletons in cephalic presentation, the rate of metabolic acidosis with pH < 7.10 and BE < -5 mmol/L in umbilical arterial blood roughly doubled between the periods 2008-2010 and 2020-2022.


Apgar Score , Umbilical Arteries , Humans , Germany/epidemiology , Infant, Newborn , Hydrogen-Ion Concentration , Female , Pregnancy , Live Birth/epidemiology , Male , Cohort Studies , Fetal Blood/chemistry , Retrospective Studies
19.
Vet Res Commun ; 48(3): 1545-1561, 2024 Jun.
Article En | MEDLINE | ID: mdl-38379058

The current study aimed to investigate the effect of xylazine sedation (non-sedated versus sedated conditions) and animal temperament on the fetal and maternal hemodynamics during the late stage of gestation in goats. In addition, it aimed to study the concentrations of cortisol and the echotexture of the placentome. Fourteen goats were assigned into two equal groups (n = 7, each) based on the animal's emotional temperament (calm versus nervous groups). All goats were examined for assessment of the blood flow within the fetal aorta (FA), umbilical artery (UMA), and middle uterine artery (MUA) using color-pulsed Doppler ultrasonography. Goats were exposed to light sedation using the recommended dose of xylazine (0.05 mg/Kg Bw) intramuscularly. Goats in each group were reassessed for the studied parameters after sedation. Blood samples were drawn to determine the concentrations of cortisol. Placentome echotexture pixel intensity (PXI) was evaluated using computer image analysis software. Results revealed the significant impact of the xylazine sedation on the Doppler indices of the blood flow within the measured arteries (FA, UMA, and MUA), the PXI of placentome echotexture, and cortisol concentrations. The emotional temperament of goats had significant effects on the blood flow parameters of the MUA and UMA, concentrations of cortisol, and the PXI of the placentome. The interaction effect (sedation x temperament) was noticed in the measured parameters of the UMA blood flow, fetal heart rate, and cortisol concentrations. In conclusion, xylazine sedation and emotional temperaments induced alterations in the echotexture of the placentomes as well as the hemodynamic parameters of late-stage pregnant goats without affecting the pregnancy outcomes.


Goats , Placenta , Xylazine , Animals , Female , Goats/physiology , Pregnancy , Placenta/blood supply , Placenta/drug effects , Xylazine/pharmacology , Xylazine/administration & dosage , Hydrocortisone/blood , Temperament/physiology , Umbilical Arteries/diagnostic imaging , Umbilical Arteries/drug effects , Umbilical Arteries/physiology , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/administration & dosage , Fetus/blood supply , Fetus/physiology , Fetus/drug effects
20.
Fetal Diagn Ther ; 51(3): 300-309, 2024.
Article En | MEDLINE | ID: mdl-38368864

INTRODUCTION: The aim of the study was to identify predictors of poor outcomes in monochorionic diamniotic twin (MCDA) pregnancies with selective fetal growth restriction (sFGR), irrespective of the umbilical artery (UA) Doppler abnormalities. METHODS: Single-center retrospective analysis of MCDA twins diagnosed with sFGR that opted for expectant management between 2010 and 2021. The presence of any of the following variables in the growth-restricted fetus: low amniotic fluid volume (DVP ≤2 cm), lack of a cycling bladder, absent or reversed flow in the ductus venosus (DV) with atrial contraction, and elevated middle cerebral artery peak systolic velocity (MCA-PSV) defined as ≥1.50 multiples of the median was categorized as complicated. sFGR cases were classified as simple in the absence of the above-mentioned variables. RESULTS: Overall, 63.3% of cases qualified as simple, and 36.7% were complicated. Intertwin EFW discordance was higher in the complicated category (26 vs. 33%, p = 0.0002). The median gestational age at delivery was earlier (33 weeks vs. 30.5 weeks, p = 0.002), and the likelihood of survival was lower in the complicated category (p < 0.0001). The likelihood of two survivors to discharge was lower in type I complicated cases (70% in complicated type I vs. 97.1% in simple type I, p = 0.0003). On logistic regression analysis, an increase in the "complicated" score negatively correlated with two survivors to discharge (p < 0.0001). An ROC curve was created, and the AUC was 0.79. Increasing intertwin EFW discordance also decreased the probability of two survivors to discharge. CONCLUSION: The presence of oligohydramnios, lack of a cycling bladder, abnormal DV Doppler, and elevated MCA-PSV in the growth restricted fetus is associated with poor perinatal outcomes and a lower likelihood of having two survivors to discharge. The addition of intertwin EFW discordance to these variables helped improve the survival predictability.


Fetal Growth Retardation , Pregnancy, Twin , Ultrasonography, Prenatal , Humans , Female , Pregnancy , Retrospective Studies , Fetal Growth Retardation/diagnostic imaging , Fetal Growth Retardation/physiopathology , Adult , Pregnancy Outcome/epidemiology , Umbilical Arteries/diagnostic imaging , Twins, Monozygotic , Gestational Age
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