Search Results (30)

Objective: To describe first-trimester maternal, biochemical, biophysical, and ultrasound characteristics in women with recurrent pregnancy loss (RPL) compared to women without RPL. Methods: This was a retrospective cohort study analyzing data from 4440 pregnant women, including 142 women with previous RPL. Maternal and pregnancy characteristics, first-trimester biochemical markers, biophysical assessments, early-onset preeclampsia (EOPE) risk, and perinatal outcomes were compared. Results: Women with RPL were older (37.8 vs. 34.0 years, p < 0.001) and had higher rates of antiphospholipid syndrome (4.9% vs. 0.9%, p < 0.001), other thrombophilias (5.6% vs. 0.8%, p < 0.001), and thyroid disorders (14% vs. 7.5%, p = 0.010) than women without RPL. First-trimester uterine artery pulsatility index (UtA-PI) values, pregnancy-associated plasma protein-A (PAPP-A) levels, mean arterial pressure, and final risk for EOPE were comparable between groups. However, the RPL group had higher rates of very high risk for PE (10.6 vs. 5.1, p = 0.011). Likewise, second-trimester UtA-PI was higher in this group (1.10 vs. 1.01, p = 0.045). Aspirin and low molecular weight heparin prophylaxis were more frequent in women with RPL (23.8% vs. 9.6%, p < 0.001; 14.7% vs. 0.1%, p < 0.001). Regarding perinatal outcomes, we found a higher incidence of second-trimester intrauterine demise in the RPL group (6.4% vs. 1.4%, p = 0.011), with no other differences observed in the remaining outcomes. Conclusions: Women with RPL exhibit distinct maternal characteristics and worse pregnancy outcomes, although first-trimester markers do not seem to significantly differ from findings in women without RPL. These findings underscore the importance of tailored screening and intervention protocols to improve perinatal outcomes in this high-risk population. Full article

Background/Objective: Preeclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. Early prediction is crucial for timely intervention and management. The ophthalmic artery (OA) Doppler assessment in the first trimester has emerged as a potential tool for predicting PE, particularly early PE, with delivery <37 weeks of gestation. This study aimed to evaluate and compare the relationship of ophthalmic artery Doppler parameters at 11–13 weeks of gestation with the subsequent development of early and late PE. Methods: A prospective observational analysis was conducted on 4054 pregnant women, including 114 who developed PE. OA Doppler assessment of the pulsatility index (PI) and peak systolic velocity (PSV) ratio, mean arterial pressure (MAP), uterine artery PI (UtA-PI), and serum placental growth factor (PlGF) were compared between women who later developed early PE and late PE with those who did not develop PE. Results: In the PE groups, particularly those with early PE, compared to the no PE group, the OA PSV ratio and UtA-PI were higher and PlGF was lower. Conclusion: A first-trimester OA Doppler assessment shows promise as a non-invasive method for the prediction of PE. Further prospective, multicenter studies are needed to validate these findings. Full article

Background: We assessed the relationship between uterine artery (UtA) indices and the occurrence of obstetrical complications in twin pregnancies. Methods: It was a longitudinal, prospective observation of the UtA indices and obstetric outcomes in twin pregnancies between 11 weeks of gestation and delivery. We used a logistic regression model with reliable estimators of standard errors considering the longitudinal structure. In 150 patients with twin pregnancies, 1086 ultrasound examinations were performed. The analysis incorporated nomograms for singletons and dichorionic (DC) twins. Results: In twin pregnancies, we observed a positive relationship between UtA indices and obstetrical complications (OR = 1.32, p = 0.043 for standardized PI and OR = 1.38, p = 0.018 for standardized RI). The risk increased with increasing UtA indices. There was a significant positive relationship between the UtA indices and analyzed pathologies in DC twins. We observed that both DC twins’ UtA indices below the 5th percentile were associated with favorable outcomes, while those above the 95th percentile were associated with adverse outcomes. According to the singleton nomograms, only the UtA PI above the 95th percentile showed significance. In MC twins, only significantly elevated UtA indices above the upper limit of nomogram were associated with adverse outcomes. Conclusions: The UtA nomogram for singleton and DC twins may be used in the prediction of twin pregnancy outcome, but DC nomograms are more accurate. The mechanism of obstetric complications in MC twins differs, and it requires further research. However, it seems that DC twin nomograms can be used in MC twins, but they will be less effective. Full article

Background and Objectives: Pregnancies resulting from assisted reproductive technology (ART) have been associated with placenta-related adverse outcomes. Uterine artery Doppler pulsatility index (UtA-PI) reflects placental function. This study aimed to examine whether second-trimester UtA-PI differs according to the conception method after adjusting for potential confounding factors. Materials and Methods: In this retrospective cohort study, we included data from February 2015 to August 2024, at the third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, on singleton pregnancies presenting for their routine antenatal care, including a second-trimester anomaly scan. Pregnancies conceived via ART, including those conceived via ovulation induction/intrauterine insemination (OI/IUI) or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), were compared to those conceived spontaneously. Multiple linear regression was employed to investigate the association between the mode of conception and log₁₀ UtA-PI values, adjusting for various confounders, including gestational age at the time of the scan, maternal weight, height, age, parity, mode of delivery, smoking status, pre-existing diabetes mellitus (type I or II), and pre-existing thyroid disease. Results: The study included 15,552 singleton pregnancies, of which 82 (0.5%) were conceived via OI/IUI and 690 (4.4%) were conceived via IVF/ICSI. The median UtA-PI values were 0.99 (IQR: 0.85–1.17) for spontaneous conception (SC), 1.00 (IQR: 0.86–1.16) for OI/IUI, and 0.90 (IQR: 0.76–1.12) for IVF/ICSI. The Kruskal–Wallis test indicated a statistically significant difference among these groups (p < 0.001). Pairwise comparisons using the Wilcoxon rank-sum test with Bonferroni correction revealed that UtA-PI values in IVF/ICSI pregnancies were significantly lower compared to both SC and OI/IUI pregnancies (p < 0.001 for both). No significant difference was observed between the SC and OI/IUI groups. In the multivariable linear regression model, IVF/ICSI conception was independently associated with lower log₁₀ UtA-PI values (estimate = −0.076, 95% CI: −0.096, −0.056) while no association was found for OI/IUI conception. Conclusions: Although ART has been associated with placental-related complications, mid-trimester UtA flow was found to be lower in IVF/ICSI pregnancies, suggesting better utero-placental flow in ART pregnancies and other possible mechanisms in the maternal–placental interplay for the development of pregnancy complications. Full article

Background and Objectives: This meta-analysis aimed to determine whether pre-implantation uterine artery (UtA) Doppler measurements are associated with clinical pregnancy in women undergoing assisted reproductive technologies (ART). Materials and Methods: A systematic search of MEDLINE, Scopus, and the Cochrane Library from inception until 25 March 2025 was conducted to identify relevant studies. Additional records were retrieved through grey literature searching and manual reference checks. Eligible publications were observational studies or clinical trials that evaluated UtA Doppler indices prior to embryo transfer in adult women undergoing ART. Studies were required to report on clinical pregnancy rates, while those enrolling participants under 18 years of age, lacking Doppler data, or providing no pregnancy endpoints were excluded. Three reviewers independently assessed study quality using the Newcastle–Ottawa Scale and the Quality in Prognosis Studies tool. Meta-analyses were performed using a random-effects model to calculate mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was examined via Cochran’s Q and the I² statistic. Sensitivity analyses excluded studies at high risk of bias. Results: In total, 12 studies met the inclusion criteria, including a population of 3317 women. Women who achieved clinical pregnancy had a lower mean UtA pulsatility index (PI) (MD, −0.26; 95% CI, −0.46 to −0.06) and a higher peak systolic velocity (PSV) (MD, 8.59; 95% CI, 2.31 to 14.87) than those who did not conceive. Subgroup analyses showed that UtA PI measured during the menstrual cycle was lower in clinical pregnancy cases (MD, −0.38; 95% CI, −0.66 to −0.10). Measurements on the day of hCG administration or the day before showed a non-significant difference in UtA PI (MD, −0.43; 95% CI, −1.03 to 0.17), while assessments on the day of embryo transfer showed no significant difference between groups (MD, −0.02; 95% CI, −0.28 to 0.24). Conclusions: This meta-analysis suggests that lower UtA PI and higher PSV prior to embryo transfer are associated with higher clinical pregnancy rates in ART, particularly when measurements are taken during the menstrual cycle. Although these findings highlight a potential role for uterine hemodynamics in successful clinical pregnancy, UtA Doppler alone may not be a reliable predictor. Future studies should focus on earlier-cycle Doppler measurements and their integration into multifactorial models to improve prognostic accuracy. Full article

Gut-derived uremic toxins (UTs) contribute to cardiovascular disorders like atherosclerosis and cardiomyopathy in patients with chronic kidney disease (CKD), causing increased cardiovascular morbidity and mortality. The intermediate steps between higher concentrations of gut-derived UTs and organ damage caused by UTs are still insufficiently understood. Glycosaminoglycans (GAGs) as components of the extracellular matrix are known to interact with various ligands such as growth factors or receptors, thereby influencing (patho)physiological processes. We previously found that the UT inorganic phosphate (Pi) induces the synthesis and sulphation of the GAGs heparan sulphate and chondroitin sulphate in the rat vascular smooth muscle cell (VSMC) line A7r5 and in the human endothelial cell (EC) line EA.Hy926. The aim of this study was to investigate if other organic UTs modulate GAGs in vascular cells as well. We treated ex vivo cultures of rat aortic rings as well as primary rat VSMCs and human ECs with the UTs Pi, indoxylsulphate (IS), p-cresylsulphate (pCS), trimethylamine N-oxide (TMAO), and urea, and analyzed the samples by histological staining, qPCR, western blot, HPLC, and colorimetric assays. The UT treatment of aortic rings and cells increased contents of sulphated GAGs and hyaluronic acid. UT-treated cells contained higher amounts of 4S- and 6S-sulphated GAGs compared to controls. This was accompanied by altered expressions of genes and proteins relevant for GAG metabolism. Mechanistically, the effects of the UTs on GAGs involve the activation of the PI3K/Akt pathway and of the transcription factor NF-κB. In conclusion, the UT-induced remodeling of the cardiovascular matrix by upregulation of sulphated GAGs and hyaluronic acid in aortic tissue and vascular cells might be a missing link between gut-derived UT and pathophysiological alterations in the cardiovascular system in the sense of a gut–matrix axis. Full article

Objectives: The aim of this study was to investigate the factors associated with the prediction of perinatal survival in pregnancies with extreme preterm delivery between 24⁺⁰ and 27⁺⁶ weeks’ gestation. Methods: This screening cohort study was undertaken at a large tertiary obstetric and neonatal unit in the United Kingdom. We included singleton pregnancies that booked and delivered at our hospital. Logistic regression analysis was carried out to determine risks of complications in pregnancies delivering preterm after adjusting for maternal and pregnancy characteristics. Effect sizes were expressed as absolute risks (ARs) and odds ratios (ORs) (95% confidence intervals [CI]). Results: The study population included 53,649 singleton pregnancies, including 139 (0.3%) with preterm delivery between 24⁺⁰ and 27⁺⁶ weeks and 47,006 (99.7%) with term delivery ≥37 weeks. Multivariate regression analysis demonstrated that there was a significant contribution of uterine artery pulsatility index (UtA-PI) and cervical length, but not of maternal factors, in the prediction of preterm delivery <28 weeks. The risk of neonatal death and intact neurological survival in pregnancies delivering <28 weeks was 11.5% and 79.1%, respectively. Caesarean compared to vaginal delivery and female compared to male neonates were associated with a lower incidence of neurological morbidity (6.1% vs. 19.3%; p = 0.016 and 13.1% vs. 26.9%; p = 0.036, respectively). In the prediction of intact perinatal survival, the only significant variable was gestational age at delivery, with survival rates of about 50%, 65%, 80% and 90% at 24, 25, 26 and 27 weeks, respectively. Conclusions: In pregnancies with extreme preterm delivery between 24⁺⁰ and 27⁺⁶ weeks, caesarean compared to vaginal delivery and female compared to male neonates are associated with a lower incidence of neurological morbidity. The only significant factor in the prediction of intact perinatal survival is gestational age at delivery. Full article

Background and Objectives: To evaluate the diagnostic accuracy of widely available biomarkers longitudinally measured throughout pregnancy to predict all and term (delivery at ≥37 weeks) preeclampsia (PE). Materials and Methods: This is a longitudinal retrospective study performed at Hospital Universitario de Torrejón (Madrid, Spain) and Shterev Hospital (Sofia, Bulgaria) between August 2017 and December 2022. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination and first-trimester screening for preterm PE at 11 + 0 to 13 + 6 weeks’ gestation at the participating centers were invited to participate in a larger study for the prediction of pregnancy complications. The dataset was divided into two subsets to develop and validate a joint model of time-to-event outcome and longitudinal data, and to evaluate how the area under the receiving operating characteristic curve (AUROC) evolved with time. Results: 4056 pregnancies were included in the training set (59 all PE, 40 term PE) and 944 in the validation set (23 all PE, 20 term PE). For the joint model and all PE, the AUROC was 0.84 (95% CI 0.73 to 0.94) and the detection rate (DR) for a 10% screening positive rate (SPR) was 56.5 (95% CI 34.5 to 76.8). For term PE, AUROC was 0.80 (95% CI 0.69 to 0.91), and DR for a 10% SPR was 55.0 (95% CI 31.5 to 76.9). The AUROC using only information from the first trimester was 0.50 (95% CI 0.37 to 0.64) and it increased to 0.84 (0.73 to 0.94) when using all information available. Conclusions: Routinely measuring MAP and UtA-PI throughout pregnancy may improve the predictive prediction power for all and term-PE. Full article

Background: SCUBE-1 (Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-domain-containing protein 1) is a novel marker of ischemia, which is a cell surface-secreted protein in the platelets and endothelial cells. The aim of the study is to measure serum SCUBE-1 levels and investigate their association with uteroplacental blood flow in patients with preeclampsia. Methods: The study was conducted on patients with preeclampsia. Maternal serum SCUBE1 and IMA levels were the main outcomes. The control group consisted of gestational-age-matched pregnant women. Fetal umbilical artery (UA) pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio (CPR), and maternal uterine artery (UtA)-PI were also examined, and correlation analysis was performed to reveal the association between maternal serum SCUBE1 levels and Doppler findings. Results: The study group consisted of thirty-two preeclamptic patients, and the control group consisted of thirty-two uncomplicated singleton pregnancies. Maternal serum SCUBE1 and IMA levels were significantly higher in preeclamptic women compared to the control group (p < 0.000, p < 0.004, respectively). Mean UtA-PI values and fetal UA-PI values were significantly higher in preeclamptic pregnant women compared to the control group (p < 0.05, p < 0.05, respectively). However, the average CPR was significantly lower in pregnant women with preeclampsia (p < 0.05). While no significant correlation was found between maternal serum SCUBE1 levels and UA-PI and CPR (p > 0.05, p > 0.05, respectively), a significant correlation was found between right and left UtA-PI (p < 0.004, p < 0.006, respectively). Conclusions: The maternal serum SCUBE1 level is increased in patients with preeclampsia, and this increase is significantly correlated with the maternal uterine artery pulsatility index. Full article

Traumatic damage to the spinal cord (SCI) frequently leads to irreversible neurological deficits, which may be related to apoptotic neurodegeneration in nerve tissue. The MLC901 treatment possesses neuroprotective and neuroregenerative activity. This study aimed to explore the regenerative potential of MLC901 and the molecular mechanisms promoting neurogenesis and functional recovery after SCI in rats. A calibrated forceps compression injury for 15 s was used to induce SCI in rats, followed by an examination of the impacts of MLC901 on functional recovery. The Basso, Beattie, and Bresnahan (BBB) scores were utilized to assess neuronal functional recovery; H&E and immunohistochemistry (IHC) staining were also used to observe pathological changes in the lesion area. Somatosensory Evoked Potentials (SEPs) were measured using the Nicolet^® Viking Quest™ apparatus. Additionally, we employed the Western blot assay to identify PI3K/AKT/GSK-3β pathway-related proteins and to assess the levels of GAP-43 and GFAP through immunohistochemistry staining. The study findings revealed that MLC901 improved hind-limb motor function recovery, alleviating the pathological damage induced by SCI. Moreover, MLC901 significantly enhanced locomotor activity, SEPs waveform, latency, amplitude, and nerve conduction velocity. The treatment also promoted GAP-43 expression and reduced reactive astrocytes (GFAP). MLC901 treatment activated p-AKT reduced p-GSK-3β expression levels and showed a normalized ratio (fold changes) relative to β-tubulin. Specifically, p-AKT exhibited a 4-fold increase, while p-GSK-3β showed a 2-fold decrease in T rats compared to UT rats. In conclusion, these results suggest that the treatment mitigates pathological tissue damage and effectively improves neural functional recovery following SCI, primarily by alleviating apoptosis and promoting neurogenesis. The underlying molecular mechanism of this treatment mainly involves the activation of the PI3K/AKT/GSK-3β pathway. Full article

Background: The examination of the uterine arteries using Doppler in the first trimester of pregnancy serves as a valuable tool for evaluating the uteroplacental circulation. Diabetes mellitus is associated with altered placental implantation and pregnancy-related pathologies, such as preeclampsia. The aim of this study was to compare the uterine arteries’ pulsatility indices (UtA PI) in women with diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), gestational diabetes mellitus (GDM), and uncomplicated pregnancies. Methods: This was a retrospective case–control trial including pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, presenting for first-trimester ultrasound screening in two tertiary university hospitals between 2013 and 2023. The first-trimester UtA pulsatility index (PI), expressed in multiples of medians (MoMs), was compared between the four groups. Results: Out of 15,638 pregnant women, 58 women with DM1, 67 women with DM2, 65 women with GDM, and 65 women with uncomplicated pregnancies were included. The mean UtA PI were 1.00 ± 0.26 MoMs, 1.04 ± 0.32 MoMs, 1.02 ± 0.31 MoMs, and 1.08 ± 0.33 MoMs in pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, respectively (p > 0.05). Conclusions: Potential alterations in the implantation of the placenta in pregnant women with diabetes were not displayed in the first-trimester pulsatility indices of the uterine arteries, as there were no changes between the groups. Full article

The modality of endometrial preparation for the transfer of frozen-thawed embryos may influence maternal and fetal adaptation to pregnancy and could thus impact the results of the first trimester combined screening test. We conducted a retrospective cross-sectional study on singleton pregnancies achieved by embryo transfer of a single frozen-thawed blastocyst, comparing two different endometrial preparation protocols: natural cycle (n = 174) and hormone replacement therapy (HRT) (n = 122). The primary outcome was the risk of preeclampsia at the first trimester combined screening test. Secondary endpoints included variable reflecting fetal cardiac function (nuchal translucency and fetal heart rate), maternal adaptation (median arterial blood pressure—MAP and uterine arteries pulsatility index—UtA-PI), and placentation (pregnancy associated plasma protein A and placental growth factor). The risk of early preeclampsia was comparable in the two groups (38% vs. a 28%, p = 0.12). However, women in the natural cycle group showed lower fetal heart rate (159 [155–164] vs. 164 [158–168], p = 0.002) and higher UtA-PI (0.96 [0.74–1.18] vs. 0.72 [0.58–0.90], p < 0.001). The frequency of a screening test at high risk for aneuploidies was similar. The modality of transfer of frozen-thawed embryos is associated with changes in the variables reflecting maternal and fetal cardiovascular function. Full article

Fatigue-related subchondral bone injuries of the third metacarpal/metatarsal (McIII/MtIII) bones are common causes of wastage, and they are welfare concerns in racehorses. A better understanding of bone health and strength would improve animal welfare and be of benefit for the racing industry. The porosity index (PI) is an indirect measure of osseous pore size and number in bones, and it is therefore an interesting indicator of bone strength. MRI of compact bone using traditional methods, even with short echo times, fail to generate enough signal to assess bone architecture as water protons are tightly bound. Ultra-short echo time (UTE) sequences aim to increase the amount of signal detected in equine McIII/MtIII condyles. Cadaver specimens were imaged using a novel dual-echo UTE MRI technique, and PI was calculated and validated against quantitative CT-derived bone mineral density (BMD) measures. BMD and PI are inversely correlated in equine distal Mc/MtIII bone, with a weak mean r value of −0.29. There is a statistically significant difference in r values between the forelimbs and hindlimbs. Further work is needed to assess how correlation patterns behave in different areas of bone and to evaluate PI in horses with and without clinically relevant stress injuries. Full article

Background: Nowadays, it is possible to identify a group at increased risk of preeclampsia (PE) and fetal growth restriction (FGR) using the principles of the Fetal Medicine Foundation (FMF). It has been established for several years that acetylsalicylic acid (ASA) reduces the incidence of PE and FGR in high-risk populations. This study aimed to evaluate the implementation of ASA use after the first-trimester screening in a Polish population without chronic hypertension, as well as its impact on perinatal complications. Material and methods: A total of 874 patients were enrolled in the study during the first-trimester ultrasound examination. The risk of PE and FGR was assessed according to the FMF guidelines, which include the maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtPI), pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PLGF). Among patients with a risk higher than >1:100, ASA was administered at a dose of 150 mg. Perinatal outcomes were assessed among the different groups. Results: When comparing women in the high-risk group with those in the low-risk group, a statistically significantly higher risk of pregnancy complications was observed in the high-risk group. These complications included pregnancy-induced hypertension (PIH) (OR 3.6 (1.9–7)), any PE (OR 7.8 (3–20)), late-onset PE (OR 8.5 (3.3–22.4)), FGR or small for gestational age (SGA) (OR 4.8 (2.5–9.2)), and gestational diabetes mellitus type 1 (GDM1) (OR 2.4 (1.4–4.2)). The pregnancies in the high-risk group were more likely to end with a cesarean section (OR 1.9 (1.2–3.1)), while the newborns had significantly lower weights (<10 pc (OR 2.9 (1.2–6.9)), <3 pc (OR 10.2 (2.5–41.7))). Conclusions: The first-trimester screening test for PE and FGR is a necessary and effective tool in identifying high-risk pregnancies. ASA prophylaxis among high-risk patients may have the most beneficial effect. Furthermore, this screening tool may significantly reduce the incidence of early-onset PE (eo-PE). Full article

Background and Objectives: The aim of this study was to assess the differences in Doppler indices of the uterine (Ut), umbilical (UA), and middle cerebral artery (MCA) in diabetic versus non-diabetic pregnancies by conducting a comprehensive systematic review of the literature with a meta-analysis. Materials and Methods: PubMed, Web of Science, and SCOPUS were searched for studies that measured the pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio index (S/D ratio) of the umbilical artery, middle cerebral artery, and uterine artery in diabetic versus non-diabetic pregnancies. Two reviewers independently evaluated the eligibility of studies, abstracted data, and performed quality assessments according to standardized protocols. The standardized mean difference (SMD) was used as a measure of effect size. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated by means of funnel plots. Results: A total of 62 publications were included in the qualitative and 43 in quantitative analysis. The UA-RI, UtA-PI, and UtA-S/D ratios were increased in diabetic compared with non-diabetic pregnancies. Subgroup analysis showed that levels of UtA-PI were significantly higher during the third, but not during the first trimester of pregnancy in diabetic versus non-diabetic pregnancies. No differences were found for the UA-PI, UA-S/D ratio, MCA-PI, MCA-RI, MCA-S/D ratio, or UtA-RI between diabetic and non-diabetic pregnancies. Conclusions: This meta-analysis revealed the presence of hemodynamic changes in uterine and umbilical arteries, but not in the middle cerebral artery in pregnancies complicated by diabetes. Full article