Search Results (1,380)

Background/Objectives: Hypertensive disorders of pregnancy, including pre-eclampsia and eclampsia, are leading causes of maternal morbidity and mortality worldwide and in Kazakhstan. This study aims to assess the burden of hypertensive disorders of pregnancy and main maternal disorders in Almaty, Kazakhstan, using the disability adjusted life years (DALY) methodology. Methods: We conducted a retrospective analysis of women aged 18 and above in Almaty, Kazakhstan, from 2018 to 2020. The medical claim data were retrieved from the Almaty city branch of the Republican Center for Electronic Health Care. Incidence-based DALY were calculated. Results: The total DALY increased for severe pre-eclampsia from 109.3 in 2018 to 187.2 in 2020 per 100,000 population and eclampsia from 3.1 in 2018 to 159.3 in 2020 per 100,000 population. Also, the 25–29 years age group had the largest increase in percent change (5.8) in the total DALY for hypertensive disorders of pregnancy. In addition, the 20–24 years age groups had the largest increase in percent change in the total DALY for severe pre-eclampsia (25.8) and eclampsia (80.5). Conclusions: Our findings highlight an increase in the burden of maternal disorders, especially for severe pre-eclampsia and eclampsia, in Almaty, Kazakhstan, from 2018 to 2020. Younger women bear a significant share of this burden, compounded by the pandemic’s impact on healthcare services. Full article

Background/Objectives: Obesity during pregnancy is strongly related to increased insulin resistance, and subsequent development of metabolic syndrome-like disorders, such as glucose intolerance, pre-eclampsia, as well as preterm birth, and cesarean delivery. Nutrition can influence the evolution of glycemic response and may help improve adverse pregnancy outcomes and long-term complications. The main objective of the Nutritional Intervention during Gestation and Offspring Health (NIGOHealth) randomized clinical trial (ClinicalTrials.gov Identifier: NCT02285764) was to investigate the potential effects of a low glycemic index/slow digesting (LGI/SD) carbohydrate product on maternal glycemia (glucose AUC at 27⁺⁰–28⁺⁶ weeks; maternal fasting blood glucose (MFBG) at 34⁺⁰–36⁺⁰ weeks), and neonatal body composition. Methods: Obese pregnant women were randomized: 230 in the intervention group (IG), who consumed two servings of an LGI/SD study product daily from 15 weeks of pregnancy until delivery, and 102 participants in the Standard of Care (SOC) group. Results: When analyzing baseline characteristics, significant differences were found in glucose metabolic parameters with higher values for IG than for the SOC group, compromising the group’s comparability. Despite this, a statistical analysis was conducted (intention-to-treat analysis/evaluable cohort): no differences were detected regarding maternal blood glucose AUC at 27⁺⁰–28⁺⁶ weeks, nor for MFBG at 34⁺⁰–36⁺⁰ weeks. Nonetheless, HbA1c (%) at 34⁺⁰–36⁺⁰ weeks was significantly lower in the IG vs. the SOC group (5.26 ± 0.03, 5.31 ± 0.04, p = 0.007) after adjusting for baseline conditions. Conclusion: This result might suggest a potential effect of the intervention on Evaluable participants. However, it should be taken with caution, due to the limitations of the study. More RCTs should be carried out to explore the effects of LGI/SD products on glycemic response in obese pregnant women. Full article

PLAC8, expressed by interstitial extravillous trophoblasts (iEVTs), plays a crucial role in trophoblast invasion, differentiation, and immunotolerance. Its dysregulation may contribute to pregnancy complications, such as preeclampsia. This study investigates the role of PLAC8 in trophoblast invasiveness and endothelial-like differentiation under different oxygen tensions. Swan-71 cells were transiently transfected with PLAC8 overexpression or knockdown plasmids. Invasion was assessed using Matrigel-coated transwells, endothelial-like differentiation through tube formation assays, and vasculogenic marker expression (VEGF, PGF, ANGPT2) by RT-PCR. Hypoxia experiments were performed at different oxygen conditions. PLAC8 overexpression enhanced trophoblast invasion but reduced endothelial-like differentiation, downregulating VEGF and PGF while upregulating ANGPT2. Hypoxia increased PLAC8 expression, indicating oxygen tension as a regulatory factor. PLAC8 manipulation did not affect cell viability. PLAC8 modulates trophoblast behavior by promoting invasion while inhibiting endothelial-like differentiation. Its regulation of vasculogenic and angiogenic factors suggests a critical role in placental homeostasis and potential relevance to pregnancy disorders, such as preeclampsia. Full article

Background/Objective: Preeclampsia is a hypertensive disorder associated with pregnancy that has a significant impact on maternal and neonatal health and has the potential to result in significant perinatal adverse outcomes. Maternal education has been proposed as a protective factor during pregnancy; however, its role in preeclamptic pregnancies remains unclear. This study aimed to explore the relationship between maternal education level, as defined by ISCED classification, and neonatal outcomes (birth weight, gestational age, and APGAR score) in pregnancies complicated by preeclampsia. Methods: A retrospective case-control analysis was conducted on 674 deliveries at a single tertiary center in Western Romania between January 2022 and August 2024. Neonatal outcomes, specifically birth weight, gestational age, and APGAR scores were studied and stratified into three ISCED-based maternal education subgroups. Statistical analyses, including ANOVA, chi-square tests, and logistic regression, were used to analyze the effect of maternal education, with confounders such as maternal age and chronic hypertension being controlled for. Results: Preeclampsia was associated with lower birth weight (p < 0.001), gestational age at birth (p < 0.001), and APGAR scores (p < 0.001) than the control group. Maternal level of education was associated with better neonatal outcomes in the preeclamptic group, with lower odds of fetal growth restriction (OR = 0.68, p = 0.03) and preterm birth; however, the effect was less pronounced in the control group. Conclusions: Maternal education partially mitigates the adverse effects of preeclampsia on neonatal well-being, birth weight, and gestational age at birth. These findings underscore the importance of incorporating maternal education into prenatal care programs to improve perinatal outcomes, with a special focus on high-risk pregnancies. Full article

Background/Objectives: The retinal microvasculature may reflect systemic vascular health and can be non-invasively imaged using optical coherence tomography angiography (OCTA). Investigation of the capillary plexuses in the macula and the peripapillary area could potentially provide insights into the pathophysiology of ocular manifestations in preeclampsia. We aimed to review the literature on OCTA metrics in preeclampsia to evaluate its use in this condition. Methods: A literature search was performed using the PubMed database, and studies published up to December 2024 were included. Results: We summarized the current evidence on chorioretinal microvascular changes in pregnancy and the ocular manifestations of preeclampsia. We reported findings from seven published studies characterizing the chorioretinal capillary plexuses in preeclampsia using OCTA. These revealed changes in microvasculature characteristics, such as foveal avascular zone size and vessel density in the macula and the peripapillary area; however, there was variability in reported parameters. Conclusions: Microvascular changes in the chorioretinal capillary plexus in preeclampsia were reported by several studies; however, results were inconsistent and may have been affected by multiple factors. Nevertheless, OCTA may have diagnostic and prognostic value, by providing evidence of microcirculation sequalae and aiding our understanding of ocular manifestations in this condition. Further studies are warranted to establish appropriate OCTA acquisition protocols and metrics, and whether these could guide clinical practice in preeclampsia. Full article

Background/Objectives: Adverse pregnancy outcomes (APOs), which include hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, and related disorders), gestational diabetes, preterm birth, fetal growth restriction, low birth weight, small-for-gestational-age newborn, placental abruption, and stillbirth, are health risks for pregnant women that can have fatal outcomes. This study’s aim is to investigate the usefulness of artificial intelligence (AI) in improving these outcomes and includes changes in the utilization of ultrasound, continuous monitoring, and an earlier prediction of complications, as well as being able to individualize processes and support clinical decision-making. This study evaluates the use of AI in improving at least one APO. Methods: PubMed, Web of Science, and Scopus databases were searched and limited to the English language, humans, and between 2020 and 2024. This scoping review included peer-reviewed articles across any study design. However, systematic reviews, meta-analyses, unpublished studies, and grey literature sources (e.g., reports and conference abstracts) were excluded. Studies were eligible for inclusion if they described the use of AI in improving APOs and the associated ethical issues. Results: Five studies met the inclusion criteria and were included in this scoping review. Although this review initially aimed to evaluate AI’s role across a wide range of APOs, including placental abruption and stillbirth, the five selected studies focused primarily on preterm birth, hypertensive disorders of pregnancy, and gestational diabetes. None of the included studies addressed placental abruption or stillbirth directly. The studies primarily utilized machine-learning models, including extreme gradient boosting (XGBoost) and random forest (RF), showing promising results in enhancing prenatal care and supporting clinical decision-making. Ethical considerations, including algorithmic bias, transparency, and the need for regulatory oversight, were highlighted as critical challenges. Conclusions: The application of these tools can improve prenatal care by predicting obstetric complications, but ethics and transparency are pivotal. Empathy and humanization in healthcare must remain fundamental, and flexible training mechanisms are needed to keep up with rapid innovation. AI offers an opportunity to support, not replace, the doctor–patient relationship and must be subject to strict legislation if it is to be used safely and fairly. Full article

Background/Objectives: Preeclampsia is a multifactorial disorder with a possible genetic component. While numerous studies have explored genetic susceptibility, validation remains inconsistent. The aim was to assess the association between hypertension-related polymorphisms and preeclampsia risk. Methods: A case–control study was conducted in Karaganda, Kazakhstan (n = 95). Sixty SNPs were genotyped using the QuantStudio™ 12K Flex system. Genotype–phenotype associations were evaluated using five inheritance models and statistical analysis in R. Results: Significant associations were found for rs2516839 (C/T: OR = 5.28; 95% CI: 1.53–18.15), rs17672135 (T/T: OR = 3.48; CI: 1.05–11.5), and rs10757278 (A/G: OR = 0.3; CI: 0.11–0.83). However, wide confidence intervals suggest potential limitations in sample size and generalizability. Conclusions: While these polymorphisms show promise as genetic markers of preeclampsia risk, their clinical application requires further validation in larger, multi-ethnic cohorts. Full article

Background: Mitochondria are essential for placental function as they regulate energy metabolism, oxidative balance, and apoptotic signaling. Increasing evidence suggests that placental mitochondrial dysfunction may play a role in the development of many poor perinatal outcomes, including preeclampsia, intrauterine growth restriction (IUGR), premature birth, and stillbirth. Nonetheless, no systematic review has thoroughly investigated this connection across human research. This study aims to consolidate evidence from human research concerning the link between placental mitochondrial dysfunction and negative birth outcomes. Methods: A systematic search of PubMed, Scopus, and Web of Science identified human research examining placental mitochondrial features (e.g., mtDNA copy number, ATP production, oxidative stress indicators) in connection with adverse pregnancy outcomes. Methodological variety resulted in narrative data extraction and synthesis. Results: Twenty-nine studies met the inclusion criteria. Mitochondrial dysfunction was consistently associated with PE, IUGR, FGR, and PTB. The most often observed outcomes included diminished mtDNA copy number, decreased ATP production, elevated reactive oxygen species (ROS), and disrupted mitochondrial dynamics, characterized by increased DRP1 and decreased MFN2. Early-onset preeclampsia and symmetric fetal growth restriction exhibited particularly severe mitochondrial abnormalities, indicating a primary placental origin of the condition. Conclusions: A significant factor contributing to adverse pregnancy outcomes is the dysfunction of placental mitochondria. The analogous molecular signatures across many disorders suggest promising avenues for developing targeted therapies aimed at improving maternal–fetal health and predictive biomarkers. Full article

Pregnancy orchestrates profound neurological, hormonal, and anatomical transformations in the maternal brain, preparing it for caregiving and infant bonding. Neuroimaging reveals structural changes such as gray matter reductions and white matter reorganization during pregnancy, followed by partial recovery postpartum. These adaptations are modulated by fluctuating levels of estradiol, progesterone, prolactin, and oxytocin, which coordinate neuroplasticity and behavioral readiness. At the molecular and cellular levels, pregnancy hormones drive synaptic remodeling, neurogenesis, and glial activity. Together, these changes support maternal motivation, attachment, and responsiveness, highlighting the maternal brain’s dynamic plasticity across gestation and the postpartum period. Also, pregnancy induces profound physiological changes, particularly in vascular, hormonal, and neurologic systems, to support maternal and fetal health. While these adaptations are essential, they can predispose pregnant individuals to various neurologic and ophthalmic pathologies. This review explores how pregnancy-related changes—including hypercoagulability, pituitary enlargement, hormonal fluctuations, and immunological modulation—contribute to conditions such as stroke, idiopathic intracranial hypertension, preeclampsia-associated visual disturbances, and demyelinating disorders like neuromyelitis optica spectrum disorder and multiple sclerosis. Additionally, ocular manifestations of systemic diseases like diabetic retinopathy and thyroid orbitopathy are discussed. Understanding these complex interactions is critical for prompt recognition, accurate diagnosis, and appropriate management of vision-threatening and neurologically significant complications during pregnancy. Nevertheless, many aspects of physiological and pathological changes during and after pregnancy remain unknown and warrant further investigation. Full article

Background: Vitamin D deficiency (VDD) during pregnancy has been associated with various obstetric complications, including preeclampsia, gestational diabetes, and premature rupture of membranes. However, its potential link to placental abruption remains underexplored. The aim of this study was to investigate whether low maternal vitamin D levels are associated with an increased risk of placental abruption in pregnancies considered otherwise low-risk. Methods: We conducted a cross-sectional study involving 248 pregnant women who were admitted for delivery at a public hospital in Athens, Greece. Serum levels of 25-hydroxyvitamin D [25(OH)D] were measured upon admission. Levels below 30 ng/mL were classified as insufficient. Although this threshold corresponds to insufficiency according to the Endocrine Society, for the purposes of this study, levels < 30 ng/mL were treated as indicative of vitamin D deficiency in order to capture broader physiological implications. Cases of placental abruption were identified based on obstetric history and clinical documentation at the time of delivery. A Chi-square test was used to assess the association between vitamin D status and placental abruption, and a multivariate logistic regression model was applied to control for potential confounders, including hypertensive disorders of pregnancy, smoking, and preterm birth. The potential role of vitamin D supplementation during pregnancy was also explored as part of the analysis. Results: Our analysis revealed that women with VDD had a significantly higher incidence of placental abruption (p < 0.05). In the multivariate model, VDD remained an independent risk factor (adjusted OR: 3.2, 95% CI: 1.1–9.6). Additional risk factors that showed significant associations with placental abruption included pregnancy-induced hypertension and maternal smoking. Conclusions: These findings support the hypothesis that insufficient maternal vitamin D levels may contribute to adverse pregnancy outcomes, including placental abruption. Further prospective studies are warranted to clarify the causal mechanisms and to evaluate whether early detection and correction of vitamin D deficiency could serve as a preventive strategy in prenatal care. Full article

Background: The aim of this study was to compare the levels of Neuropilin-1 (NRP-1) in maternal plasma and fetal cord blood plasma between pregnancies complicated by preeclampsia (PE) and those in normotensive pregnant women. Materials and Methods: This prospectively designed study included 53 pregnant women aged 18 years or older and at least 20 weeks into gestation, who were admitted to the Maternity Department of Izmir Katip Çelebi University Atatürk Training and Research Hospital. The patient group consisted of 28 pregnant women who met the diagnostic criteria for PE, while the control group included 25 normotensive pregnant women. The diagnosis of PE was established based on the 2020 diagnostic criteria of the American College of Obstetricians and Gynecologists (ACOG). After detailed anamnesis, blood samples were collected immediately after delivery in EDTA tubes to assess serum NRP-1 levels. These samples included maternal blood, fetal cord blood, and additional tests such as CBC, liver and kidney function tests, serum electrolytes, spot urinalysis, prothrombin time (PT), and activated partial thromboplastin time (APTT). Results: There was a statistically significant difference between the two groups in terms of gestational week, presence of comorbidities, hypertension (HT), diabetes mellitus (DM), history of PE, and protein detected in spot urine examinations. Pregnant women in the PE group had significantly higher rates of comorbidities, HT, and DM compared to the control group (p < 0.001, 0.002, and 0.007, respectively). No statistically significant differences were observed between the two groups regarding hemoglobin, platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), or fetal cord plasma NRP-1 levels (p: 0.736, 0.831, 0.561, and 0.734, respectively). However, a statistically significant difference was found in maternal plasma NRP-1 levels (p: 0.02), which were lower in the control group compared to the PE group (median: 473.3 pg/mL vs. 587.7 pg/mL, respectively). The optimal cut-off value for maternal plasma NRP-1 to predict PE, with the best sensitivity and specificity, was determined to be 358.4 pg/mL. Among the study participants, 40 pregnant women had maternal plasma NRP-1 levels above the cut-off value, while 13 had levels below it. PE occurred significantly more frequently in the high NRP-1 group than in the low group. When demographic and clinical characteristics were analyzed, a statistically significant but weak positive correlation was found between body mass index (BMI) and maternal plasma NRP-1 levels (p: 0.02, Rho: 0.304). No strong or statistically significant relationships were identified with other variables. There was no significant difference in fetal cord plasma NRP-1 levels between the PE group and the normotensive group. In contrast, maternal plasma NRP-1 levels were significantly higher in the PE group. The cut-off value for maternal plasma NRP-1, providing optimal sensitivity and specificity for predicting PE, remained 358.4 pg/mL. Conclusions: While further studies involving larger cohorts of pregnant women from diverse racial backgrounds and various hospitals are needed to better understand the relationship between NRP-1 and PE, maternal NRP-1 concentration shows promise as a diagnostic marker. Full article

Background: Pre-eclampsia (PE) is a common and serious pregnancy complication, contributing significantly to maternal and neonatal morbidity and mortality. Emerging evidence suggests a potential link between vitamin D deficiency (VDD) and an increased risk of PE. However, the data remain inconclusive, and the precise role of vitamin D supplementation in preventing PE is still uncertain. This systematic review and meta-analysis aims to evaluate the association between maternal VDD and the risk of pre-eclampsia, specifically focusing on randomized controlled trials (RCTs) to assess the potential preventive effect of vitamin D supplementation during pregnancy. Methods: A systematic review and meta-analysis were conducted by reviewing RCTs that investigated the link between maternal VDD and the incidence of pre-eclampsia. The studies were sourced from major databases such as PubMed, Scopus, and Web of Science, with studies published from 2016 to 2025. A random-effects model was employed to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Results: A total of 2461 participants were included from the five RCTs. The meta-analysis revealed a significant reduction in the risk of pre-eclampsia among pregnant women receiving vitamin D supplementation (RR = 0.61, 95% CI: [0.50–0.75], p < 0.001), supporting its protective role. Subgroup analysis revealed that the association was particularly strong in women with serum vitamin D levels < 20 ng/mL. Additionally, supplementation with vitamin D showed a trend towards reducing the risk of pre-eclampsia, although the studies showed some heterogeneity regarding supplementation dosages and timing. Conclusions: This systematic review and meta-analysis provides robust evidence that maternal VDD is associated with an increased risk of pre-eclampsia. The findings suggest that correcting VDD through supplementation during pregnancy may be an effective preventive strategy to reduce the incidence of pre-eclampsia. However, further well-designed RCTs are required to determine the optimal timing, dosage, and long-term effects of vitamin D supplementation on maternal and neonatal health outcomes. Full article

Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis throughout the human body, influencing countless physiological and pathological processes, including tumor growth, preeclampsia, and retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). In DR, VEGF promotes retinal neovascularization and intraretinal fluid accumulation, leading to complications like diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Regular intravitreal anti-VEGF injections are commonly used to manage PDR and DME, though repeated treatments are often required, and efficacy can be limited. AMD, a major cause of vision loss in older adults, is characterized by either dry or wet forms. While the dry form has not been shown to be influenced by VEGF, the choroidal neovascularization of wet AMD has strong associations with VEGF. Current treatment for wet AMD consists primarily of anti-VEGF injections, the gold standard of care, but is limited by varying patient responses, as treatments are often repeated every 4-8 weeks indefinitely. This review explores the pathogenic role of VEGF in both DR and AMD, discussing the molecular mechanisms underlying these diseases and the therapeutic approaches targeting VEGF. Despite advancements, the variability in treatment responses highlights the need for continued research to develop more effective therapies to prevent vision loss and blindness associated with these retinal diseases. Full article

Extracellular vesicles (EVs) may play a role in preeclampsia (PE)-associated glomerular damage. We herein investigated the role of PE plasma EVs in triggering a detrimental crosstalk between glomerular endothelial cells (GEC) and podocytes (PODO). Clinical and laboratory variables were examined at T0 (diagnosis), T1 (delivery), and T2 (one month after delivery) in 36 PE patients and 17 age-matched controls. NanoSight and MACSPlex evaluated EV concentration, size, and phenotype. GEC and PODO were stimulated with plasma EVs to study viability, reactive oxygen species (ROS) production, permeability to albumin, endothelial-to-mesenchymal transition, and Endothelin-1 release. EV size and concentration were higher in PE than in healthy controls and in severe than in mild forms of disease. At T0, higher EV concentration correlated with proteinuria, blood pressure, uric acid, and liver enzyme levels. PE-EVs originated from leukocytes, endothelial cells, platelets, and the placenta and induced GEC and PODO damage as shown by the reduction of viability, increased ROS release, and albumin permeability. Co-culture experiments demonstrated that PE-EVs mediated a deleterious intraglomerular crosstalk through Endothelin-1 release from GEC able to down-regulate nephrin in PODO. In conclusion, we observed in PE plasma a peculiar pattern of EVs able to affect GEC and PODO functions and to induce proteinuria through Endothelin-1 involvement. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disorder and a leading cause of maternal and fetal morbidity and mortality. Impaired trophoblast invasion is a hallmark of PE, and alternative splicing (AS) is crucial for trophoblast differentiation and placental development. However, the exact mechanisms of AS in PE remain poorly understood. Methods: To elucidate AS-mediated regulatory pathways in PE, a total of 38 fresh-frozen placental samples, including 13 pre-eclampsia samples and 25 normal control samples, were collected from Renmin Hospital of Wuhan University between 1 February and 30 July 2022. We performed transcriptome sequencing of seven PE and seven normal placentas to identify differentially spliced events. After quality control and adapter trimming, raw sequencing reads were aligned to the human reference genome using STAR. Differential exon usage was analyzed using DEXSeq (version 1.36.0), and exons with an adjusted p-value < 0.05 and a fold change greater than 2 or less than 0.5 were considered significantly differentially spliced. Functional assays, including CCK8, colony formation, and cell cycle analyses, were conducted to assess trophoblast proliferation, whereas wound healing and Transwell assays were used to evaluate trophoblast migration and invasion using the HTR-8/SVneo cell line. RNA immunoprecipitation sequencing (RIP-seq) and RNA stability assays were employed to investigate mRNA interactions and stability. Results: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) emerged as a key RNA-binding protein associated with alternative splicing regulation, intersecting both AS-related candidate genes and known splicing factors, although it is not a classical splicing factor itself. IGF2BP3 overexpression markedly enhanced HTR-8/SVneo trophoblast proliferation, migration, and invasion while suppressing ROS activation. RNA-seq, RIP-seq, and RNA stability assays revealed that IGF2BP3 directly interacts with and enhances the stability of PDE3A mRNA. Functional rescue experiments confirmed that PDE3A knockdown partially abrogated IGF2BP3-mediated trophoblast progression. Furthermore, miR-196a-5p was identified as a negative regulator of IGF2BP3 via miRNA inhibitor/mimic transfection, qRT-PCR, and functional assays, confirming that miR-196a-5p overexpression downregulates IGF2BP3, thereby impairing trophoblast migration and proliferation. Notably, restoring IGF2BP3 expression reversed these inhibitory effects. Conclusions: Our findings reveal a previously unrecognized regulatory axis in PE in which miR-196a-5p suppresses IGF2BP3 expression, leading to PDE3A mRNA destabilization and impaired trophoblast function. This study offers mechanistic insights into PE pathogenesis and identifies IGF2BP3 as a potential therapeutic target. Full article