Search Results (1,316)

Background: Placental grading remains underutilized in clinical practice despite its potential prognostic value. This study aimed to elucidate the relationship between premature placental calcification (PPC) and relevant perinatal outcomes in a large cohort. Methods: We conducted a retrospective cohort study involving 3088 singleton pregnancies that underwent routine third-trimester ultrasound examinations (30⁺⁰ to 35⁺⁶ gestational weeks) at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, between January 2018 and December 2023. Placental calcification was graded using the Grannum system, categorizing placentas into Grades 0–1 (control), Grade 2, and Grade 3. Primary outcomes assessed were small for gestational age neonates (SGA) and preeclampsia. Secondary outcomes included gestational hypertension, fetal growth restriction (FGR), stillbirth, gestational age at birth, and birthweight centile. Multiple logistic regression was employed to adjust for confounders, i.e., maternal age, BMI, smoking, conception via assisted reproductive technology, and uterine artery pulsatility index. Results: In total, 544 pregnancies (17.6%) had Grade 2 placentas, and 41 pregnancies (1.3%) had Grade 3 placentas. Compared to the control group, Grade 2 placentas were associated with increased odds of SGA (adjusted odds ratio [aOR] 1.80; 95% confidence intervals [CI]: 1.43–2.25) and FGR (aOR 1.81; 95% CI: 1.35–2.42). Grade 3 placentas showed even higher odds of SGA (aOR 3.09; 95% CI: 1.55–6.17) and FGR (aOR 3.26; 95% CI: 1.53–6.95). No significant associations were found between placental grading and preeclampsia or stillbirth. Additionally, PPC was linked to lower birthweight percentiles and earlier gestational age at birth. Conclusions: Premature placental calcification (before 36⁺⁰ weeks), particularly Grade 3, is significantly associated with adverse perinatal outcomes such as SGA and FGR. Incorporating placental grading into routine prenatal care may enhance risk stratification and guide clinical decision making beyond traditional assessment methods. Full article

Gestational diabetes mellitus (GDM) is characterized by an inadequate pancreatic β-cell response to pregnancy-induced insulin resistance, resulting in hyperglycemia. The pathophysiology involves reduced incretin hormone secretion and signaling, specifically decreased glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), impairing insulinotropic effects. Pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), impair insulin receptor substrate-1 (IRS-1) phosphorylation, disrupting insulin-mediated glucose uptake. β-cell dysfunction in GDM is associated with decreased pancreatic duodenal homeobox 1 (PDX1) expression, increased endoplasmic reticulum stress markers (CHOP, GRP78), and mitochondrial dysfunction leading to impaired ATP production and reduced glucose-stimulated insulin secretion. Excessive gestational weight gain exacerbates insulin resistance through hyperleptinemia, which downregulates insulin receptor expression via JAK/STAT signaling. Additionally, hypoadiponectinemia decreases AMP-activated protein kinase (AMPK) activation in skeletal muscle, impairing GLUT4 translocation. Placental hormones such as human placental lactogen (hPL) induce lipolysis, increasing circulating free fatty acids which activate protein kinase C, inhibiting insulin signaling. Placental 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) overactivity elevates cortisol levels, which activate glucocorticoid receptors to further reduce insulin sensitivity. GDM diagnostic thresholds (≥92 mg/dL fasting, ≥153 mg/dL post-load) are lower than type 2 diabetes to prevent fetal hyperinsulinemia and macrosomia. Management strategies focus on lifestyle modifications, including dietary carbohydrate restriction and exercise. Pharmacological interventions, such as insulin or metformin, aim to restore AMPK signaling and reduce hepatic glucose output. Emerging therapies, such as glucagon-like peptide-1 receptor (GLP-1R) agonists, show potential in improving glycemic control and reducing inflammation. A mechanistic understanding of GDM pathophysiology is essential for developing targeted therapeutic strategies to prevent both adverse pregnancy outcomes and the progression to overt diabetes in affected women. Full article

Background/Objectives: Hydrogen sulfide (H₂S) is a vasorelaxant gas and exerts anti-oxidative, anti-inflammatory, and cytoprotective effects. H₂S has been implicated in regulating placental vaso-activity and angiogenesis. It is believed that abnormal trophoblast production of vasodilators and angiogenic factors contributes to pre-eclampsia development. However, little is known about whether aberrant H₂S production is present in placental trophoblasts from pre-eclamptic pregnancies. Methods: Trophoblasts were isolated from normal and pre-eclamptic placentas. After incubation, cell production of H₂S in the culture medium and the cellular levels of H₂S were analyzed by reversed phase high-performance liquid chromatography (RP-HPLC). Expression levels of the three key H₂S converting enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), were determined by immunohistochemistry. The protein expression of CBS and CSE was assessed by Western blot analysis. Results: (1) Trophoblast production and cellular levels of H₂S were significantly reduced in cells from pre-eclamptic vs. normal placentas; (2) free H₂S production was increased in a time-dependent manner in cultured trophoblasts from normal, but not from pre-eclamptic, placentas; and (3) strong CBS and CSE expression was seen in trophoblasts from normal, as opposed to pre-eclamptic, placentas. Reduced CBS and CSE expression in trophoblasts from pre-eclamptic vs. normal placentas were confirmed by Western blot analysis; and (4) 3-MST expression was undetachable in both normal and pre-eclamptic placentas, but 3-MST expression was strongly expressed in the first and second trimester placentas. Conclusions: These data provide plausible evidence that downregulation of CBS and CSE, but not 3-MST, expression may be responsible for reduced free H₂S production and decreased cellular H₂S levels in pre-eclamptic placentas. Our data provide further evidence that expression of 3-MST in placental trophoblasts is likely gestational age (developmental)-dependent. Full article

Background: The purpose of this meta-analysis was to examine the prevalence of hypertensive disorders of pregnancy (HDPs), particularly preeclampsia (PE), in peripartum cardiomyopathy (PPCM)-affected pregnancies, and to evaluate whether a HDP significantly alters the prognosis of PPCM, with specific reference to the recovery of left ventricular function (LVEF) and mortality. Methods: A total of 5468 potentially eligible studies were identified, and 104 were included in the meta-analysis. For pooling proportions, the inverse variance methods with logit transformation were used. Complete recovery of LVEF (>50%) and mortality were expressed by odds ratios (ORs), with 95% confidence intervals (CIs). The Peto OR (POR) was used in cases of rare events. Baseline LV function and baseline LV end-diastolic diameter (LVEDD) were summarized by the mean difference (MD) and 95% confidence interval (CI). Results: The summary estimate of the prevalence of HDPs and PE in women with PPCM was 36% and 25%, respectively. Patients with HDPs and, more specifically, PE with PPCM had a higher chance of complete recovery (OR = 1.87; 95%CI = 1.64 to 2.13; p < 0.001 and OR = 1.98; 95%CI 1.69 to 2.32; p < 0.001, respectively), a higher baseline LVEF (MD, 1.42; 95% CI 0.16 to 2.67; p = 0.03 and MD, 1.69; 95% CI 0.21 to 3.18; p = 0.03, respectively), and a smaller baseline LVEDD (MD, −1.31; 95% CI −2.50 to −0.13; p = 0.03 and MD, −2.63; 95% CI −3.75 to −1.51; p < 0.001, respectively). These results, however, did not translate into a significant difference in 12-month mortality (POR = 0.80; 95% CI = 0.57 to 1.13; p = 0.21 and POR = 1.56; 95% CI 0.90 to 2.73; p = 0.12, respectively). Conclusions: The findings of this study may contribute to evidence that can be utilized to aid in the risk stratification of patients with PPCM regarding their long-term prognoses. Full article

Obesity is one of the biggest health problems in the 21st century and the leading health disorder amongst women of fertile age. Maternal obesity is associated with several adverse maternal and fetal outcomes. In this group of women, the risk for the development of hypertensive disorders of pregnancy (HDPs), such as gestational hypertension (GH) and pre-eclampsia (PE), is increased. In fact, there is a linear association between an increase in pre-pregnancy body mass index (BMI) and PE. Excessive weight gain during pregnancy is also related to the development of PE and GH. The role of obesity in the pathophysiology of HDP is complex and is most likely due to an interaction between several factors that cause a state of poor maternal cardiometabolic health. Adipokines seem to have a central role in HDP development, especially for PE. Hypoadiponectinemia, hyperleptinemia, insulin resistance (IR), and a proinflammatory state are metabolic disturbances related to PE pathogenesis, contributing to its development by inducing a state of maternal endothelial dysfunction. Hypertriglyceridemia is suggested to also be a part of the disease mechanisms of HDP. Therefore, this review seeks to explore the scientific literature to assess the complications of maternal obesity and its association with the development of HDP. Full article

Placental-derived pregnancy complications encompass a range of disorders that hinder optimal fetal development, significantly impacting maternal and neonatal health outcomes. Key conditions include placental insufficiency, preeclampsia, fetal growth restriction (FGR) or intrauterine growth restriction (IUGR), fetal overgrowth, and gestational diabetes mellitus (GDM), which together contribute to a heightened risk of preterm birth, perinatal mortality, and long-term developmental challenges in affected infants. These complications are particularly notable because they generate approximately 80% of pregnancy disorders and pose significant public health concerns across diverse global contexts. Their management continues to face challenges, including a lack of consensus on diagnostic criteria and varied implementation of care standards. While imaging techniques like magnetic resonance imaging (MRI) and Doppler ultrasound have emerged as critical tools in clinical assessment, disparities in access to such technologies exacerbate existing inequalities in maternal and fetal health outcomes. Maternal and pregnancy care is a broad range of services aimed at promoting the well-being of women throughout the perinatal period. However, access to these services is often limited by economic, geographical, and sociocultural barriers, particularly for marginalized groups and women in low- and middle-income countries (LMICs). The implementation of targeted interventions designed to address specific obstacles faced by disadvantaged populations is a crucial component of bridging the gap in health equity in maternal care. Public health authorities and policymakers strive to develop evidence-based strategies that address the interplay between healthcare access, socioeconomic factors, and effective interventions in order to mitigate the adverse effects of placental-derived pregnancy complications. Continued research and data collection are essential to inform future policies and practices to improve outcomes for mothers and infants. Full article

Pregnancy involves extracellular vesicles (EVs) through mechanisms that are poorly understood to date. Furthermore, it is not surprising that EVs may also be involved in the pathophysiology of pre-eclampsia (PE) and gestational hypertension, two clinical conditions with high morbidity and mortality, given their capacity to mediate intracellular communications and regulate inflammation and angiogenesis. We searched major online scientific search engines (PubMed, Google Scholar, Scopus, WES, Embase, etc.) using the terms “Preeclampsia”, “Pregnancy”, “Hypertension”, “Pregnancy-related hypertension”, “Extracellular vesicles”, “Biomarkers”, “Gestation” AND “Obstetrics”. Finding potential early biomarkers of risk or illness progression would be essential for the optimum care of expectant mothers with the aforementioned conditions. Nevertheless, none of the various screening assays that have been discovered recently have shown high predictive values. The analysis of EVs in the peripheral blood starting from the first trimester of pregnancy may hold great promise for the possible correlation with gestational hypertension problems and represent a marker of the early stages of the disease. EVs use may be a novel therapeutic approach for the management of various illnesses, as well. In order to define EVs’ function in the physiopathology of pregnancy-associated hypertension and PE, as well as their potential as early biomarkers and therapeutic tools, we have compiled the most recent data in this review. Full article

Background/Objectives: Hypertensive disorders of pregnancy constitute one of the principal reasons for maternal and perinatal morbidity and mortality worldwide. Identification of molecular mechanisms causing placental dysfunction resulting in gestational hypertension is crucial in the development of new methods of prevention and treatment. The aim of this case-control study was to assess changes in miRNA expression, and biomarkers such as NT-proBNP and galectin-3, in women with uncomplicated pregnancies and hypertensive disorders of pregnancy. Methods: This was a case-control study. We included 61 women with uncomplicated pregnancies and 31 women with hypertensive disorders of pregnancy (21 women with gestational hypertension and 10 women with chronic hypertension). Blood sample collection was performed at 33 weeks of gestation. Expression and expression levels of 26 microRNAs, NTproBNP, and galectin-3 were measured. Results: Lower expression of microRNA 101a was observed in patients with hypertensive disorders of pregnancy. The expression of microRNA 101a was significantly lower in the group of patients with gestational hypertension, but not with chronic hypertension. Not only was the expression of microRNA 101a lower in all women with gestational hypertension but also in XYZ% it reached undetectable levels. Other studied microRNAs were similar in expression and concentration levels among both groups. In all women with hypertensive disorders of pregnancy, statistically significant correlations were detected between NT-proBNP concentrations and microRNA 133a (r = −0.68; p = 0.030) and microRNA 195 (r = 0.67; p = 0.030), and between galectin-3 and microRNA 195 (r = 0.46; p = 0.010), microRNA 133a (r = 0.44; p = 0.020), microRNA 222-2276 (r = 0.39; p = 0.050). Conclusions: microRNA 101a, a molecule associated with placental dysfunction in preeclampsia and with inhibition of cardiac fibrosis, has lower expression and concentration levels in gestational hypertension but not in chronic hypertension. Full article

Background/Objectives: High fiber (34–36 g/day) diets are recommended during pregnancy due to inverse associations with constipation and adverse pregnancy health outcomes, including pre-eclampsia and gestational diabetes. However, the mechanism for this protective effect is poorly defined. Fiber may be protective due to its impact on the composition and function of specific bacteria within the pregnancy gut microbiome. The purpose of this analysis was to investigate whether a sub-sample of cohort study participants in their third trimester met daily dietary fiber and vegetable intake recommendations and, in turn, how this impacted bacterial composition and butyrate-producing genes within the gut microbiome. Methods: Pregnant participants (n = 52) provided stool samples and survey data, which were used to calculate fiber and vegetable intake. Genomic DNA was extracted from the stool samples, followed by PCR to amplify the V4 region of the 16S rRNA gene. Amplicons were sequenced and mapped to the RDP reference. Quantitative real-time PCR was used to measure the abundance of bacterial genes for butyrate production. Results: Of the pregnant participants in this sample, 84.7% and 92.3% failed to meet recommendations in the Dietary Guidelines for Americans for dietary fiber and vegetable intake, respectively. All four participants who met the vegetable recommendation were a subset of those who met the fiber recommendation. The participants who met the pregnancy fiber recommendation had gut microbiotas with greater alpha diversity (Shannon and Inverse Simpson) than those who did not. However, there was no association between dietary fiber intake and the abundance of bacterial genes for butyrate production. Conclusions: This research suggests that general fiber intake during pregnancy has a modest association with the gut bacterial community. These preliminary results demonstrate a need to improve fiber intake during pregnancy. Further, studies that measure the relationship between dietary intake of specific types of fiber and associations with specific gut bacterial community members and their functions are needed. Full article

Background: Preeclampsia is a serious pregnancy complication known to be related to the pathophysiology of platelet dysfunction and inflammation. The aim of this study was to investigate the role of platelet indices and inflammatory markers in preeclampsia and their importance in predicting adverse neonatal outcomes. Methods: A total of 118 preeclampsia cases (84 with mild preeclampsia and 34 with severe preeclampsia) and 118 healthy pregnant women were included in the study. Blood samples obtained at the time of preeclampsia diagnosis were analyzed for platelet indices (platelet count (PC), platelet distribution width (PDW), mean platelet volume (MPV), and platelet/large cell ratio (P-LCR)) and inflammation indices (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-lymphocyte ratio (MPVLR)). Results: The PC and PLR were lower in the severe preeclampsia group compared to the other groups. The PDW was higher in both mild and severe preeclampsia groups compared to the control group. A PDW value above 13.15 was identified as a significant predictor of composite adverse neonatal outcomes (area under the curve (AUC): 0.633; sensitivity: 60.9%; specificity: 58%). Conclusions: PC and PLR decrease in severe preeclampsia. This study highlights the potential of PDW as a marker for predicting adverse neonatal outcomes in preeclampsia. Full article

Molecular biomarker profiling is an emerging field in maternal-fetal health with the potential to transform early detection and prediction of placental dysfunction. By analysing a range of biomarkers in maternal blood, researchers and clinicians can gain crucial insights into placental health, enabling timely interventions to enhance fetal and maternal outcomes. Placental structural function is vital for fetal growth and development, and disruptions can lead to serious pregnancy complications like preeclampsia. While conventional methods such as ultrasound and Doppler velocimetry offer valuable information on fetal growth and blood flow, they have limitations in predicting placental dysfunction before clinical signs manifest. In contrast, molecular biomarker profiling can provide a more comprehensive assessment by measuring proteins, metabolites, and microRNAs (miRNAs) in maternal blood, reflecting the placenta’s endocrine and metabolic functions. This approach offers a deeper understanding of placental health and function, aiding in early detection and prediction of complications. Challenges in developing molecular biomarker profiling include pinpointing specific molecular changes in the placenta linked to pathologies, timing predictions of conditions before clinical onset, and understanding how placental dysfunction affects maternal metabolism. Validating specific biomarkers and integrating them effectively into clinical practice requires further research. This review underscores the significance of molecular biomarker profiling as a powerful tool for early detection and prediction of placental dysfunction in maternal-fetal health. Through an exploration of biomarker analysis, we delve into how a deeper understanding of placental health can potentially improve outcomes for both mother and baby. Furthermore, we address the critical need to validate the utility of biomarkers and effectively integrate them into clinical practice. Full article

The global rise in obesity presents serious concerns, particularly due to its association with pregnancy complications such as gestational diabetes, preeclampsia, cesarean delivery, and fetal macrosomia. Maternal obesity also contributes to intergenerational health risks, increasing the likelihood of long-term issues in offspring. Preconception counseling is an essential preventive measure to reduce complications; however, many women miss this opportunity due to unplanned pregnancies. This study explores the impact of pregestational body mass index (BMI) and gestational weight gain (GWG) on pregnancy outcomes, underscoring the importance of routine monitoring of these parameters. Existing studies identify both BMI and GWG as independent risk factors for adverse maternal and neonatal outcomes, with elevated BMI combined with excessive GWG posing an even greater risk. Specifically, a BMI > 30 kg/m² doubles the risk of complications such as gestational diabetes, hypertension, and cesarean delivery. Additionally, a review of national and international guidelines highlights a lack of consensus on managing gestational weight gain in women with obesity, particularly regarding antepartum surveillance and timing of delivery. Similarly, no specific guidelines have been established for underweight pregnant women. Additionally, few studies have thoroughly assessed the maternal and fetal risks associated with underweight during pregnancy. Despite this, numerous studies have highlighted an increased risk of preterm birth (PTB) and small-for-gestational-age (SGA) infants. This narrative review emphasizes the need for further research to develop tailored guidelines for managing pregnant women based on pregestational BMI, ultimately improving maternal and neonatal health outcomes. Full article

Intracranial hemorrhage is a rare yet potentially devastating event during pregnancy with a significant risk of maternal and fetal mortality and morbidity. The risk of intracranial hemorrhage increases during the third trimester of pregnancy and is greatest during labor and the postpartum period. Interdisciplinary diagnosis and treatment of the pregnant population often begins in the emergency department setting and is key to increasing patient survival rates through immediate and adequate treatment, including emergency medicine, neurosurgical and obstetrical procedures. A unique case report with a diagnostic pathway for intracranial hemorrhage due to eclampsia in a primipara at 24 weeks of gestation is presented, illustrating potential diagnostic dilemmas as the patient rapidly progresses into hemolysis, elevated liver enzymes and low platelets syndrome. A literature review was conducted to uncover the etiology of intracranial hemorrhage during pregnancy, as well as its diagnostic challenges and treatment. Pregnancy should not be viewed as a barrier to performing angiography or endovascular treatment for vascular causes of intracranial hemorrhage. Patient transport to a tertiary reference center and the interdisciplinary cooperation of specialists are key to achieving correct and rapid treatment. Continuous prevention of preeclampsia and patient education are necessary to decrease the incidence of eclampsia and its complications. Key message: Intracranial hemorrhage and eclampsia in pregnant patients are rare yet may result in high rates of maternal and fetal morbidity and mortality. The diagnostic process is difficult and requires interdisciplinary cooperation to start the correct treatment immediately. Full article

Background: In vitro fertilization (IVF) has transformed infertility treatment, yet it is associated with increased risks of adverse perinatal outcomes, particularly in women of advanced maternal age. This study aimed to investigate the prevalence of complications such as preeclampsia (PE), gestational diabetes mellitus (GDM), preterm labor (PTL), low birth weight (LBW), and placental abnormalities (PA) among women over 50 undergoing assisted reproductive technology (ART) in Greece, where the eligibility age limit has been recently raised to 54 years. Methods: We conducted a retrospective analysis of pregnancy outcomes in women over 50 compared to those under 50, utilizing medical records mainly from University Hospital of Ioannina but also from other public hospitals and private clinics in Greece. Results: Our findings indicate that women over 50 face an increased risk of developing preeclampsia (PE) by 4.61 times, GDM by 1.69 times, PTL by 1.82 times, LBW by 1.67 times, and PA by 3.92 times. Conclusions: These results underscore the need for heightened awareness and the monitoring of pregnancy complications in this demographic, informing clinical strategies to improve maternal and neonatal outcomes. Full article

Preeclampsia (PE) is a complex pregnancy-specific disorder characterized by hypertension, proteinuria, and systemic inflammation, posing significant risks to maternal and fetal health. This study investigates the role of growth arrest-specific protein 6 (Gas6) in PE pathogenesis using a rat model. Gas6 administration induces hallmark PE features, including hypertension, proteinuria, and significant alterations in placental gene expression. Transcriptomic analysis revealed changes in pathways related to extracellular matrix remodeling, interleukin signaling, and oxidative stress, highlighting their contribution to PE pathology. Key findings include the upregulation of Fam111a, linked to oxidative stress and DNA replication, and the downregulation of Clca4, associated with ion transport and cellular homeostasis. Protein-level validation through immunofluorescence confirmed these alterations, reinforcing their mechanistic roles in placental dysfunction. Enrichment analysis further identified significant disruptions in extracellular matrix organization and intercellular signaling. These results underscore the pivotal role of Gas6 in exacerbating placental oxidative stress and systemic inflammation. Importantly, therapeutic inhibition of the Gas6/AXL axis using small-molecule inhibitors mitigated PE-like symptoms, highlighting its potential as a therapeutic target. This study provides novel insights into the molecular underpinnings of Gas6-mediated placental dysfunction and supports the development of targeted therapies to improve PE outcomes. Full article