Search Results (1,233)

Background/Objectives: Gestational hypertension is associated with increased maternal and fetal morbidity. The DASH diet is designed to reduce blood pressure and improve cardiovascular health. Our aim is to evaluate the efficacy of adherence to the DASH dietary pattern during pregnancy on the incidence of GH. Methods: PubMed, Scopus, Web of Science, Cochrane Library and Embase were systematically searched. All studies including data on the effect of the DASH diet on GH were included in this review. The study is registered in PROSPERO (CRD420251044348). Results: A total of five studies were included in our study. The meta-analysis reported a pooled relative risk (RR) of 1.03 (CI: 0.86–1.23) for the effect of the DASH diet on gestational hypertension. In the subgroup analysis for preeclampsia, the overall relative risk estimate was 0.78 (95% CI: 0.60–1.02). Both analyses did not yield statistical significance. Conclusions: Current evidence, although showing a favorable trend, does not conclude that the DASH diet reduces the risk of gestational hypertension, as the results did not achieve statistical significance. Although potential benefits have been observed, the limited number of available studies does not allow for definitive conclusions. More randomized and multicenter studies are needed to thoroughly investigate the relationship between the DASH diet and gestational hypertension in order to implement this dietary program instead of general dietary recommendations for GH. Full article

Pseudouridine (Ψ), the most abundant RNA modification, plays essential roles in shaping RNA structure, stability, and translational output. Beyond cancer, Ψ is dynamically regulated across numerous physiological and pathological contexts—including immune activation, metabolic disorders, stress responses, and pregnancy-related conditions such as preeclampsia—where elevated Ψ levels reflect intensified RNA turnover and modification activity. These broad functional roles highlight pseudouridylation as a central regulator of cellular homeostasis. Emerging evidence demonstrates that Ψ dysregulation contributes directly to the development and progression of several women’s cancers, including breast, ovarian, endometrial, and cervical malignancies. Elevated Ψ levels in tissues, blood, and urine correlate with tumor burden, metastatic potential, and therapeutic responsiveness. Aberrant activity of Ψ synthases such as PUS1, PUS7, and the H/ACA ribonucleoprotein component dyskerin alters pseudouridylation patterns across multiple RNA substrates, including rRNA, tRNA, mRNA, snoRNAs, and ncRNAs. These widespread modifications reshape ribosome function, modify transcript stability and translational efficiency, reprogram RNA–protein interactions, and activate oncogenic signaling programs. Advances in high-resolution, site-specific Ψ mapping technologies have further revealed mechanistic links between pseudouridylation and malignant transformation, highlighting how modification of distinct RNA classes contributes to altered cellular identity and tumor progression. Collectively, Ψ and its modifying enzymes represent promising biomarkers and therapeutic targets across women’s cancers, while also serving as sensitive indicators of diverse non-cancer physiological and disease states. Full article

Preeclampsia (PE) is the onset of hypertension in pregnancy with systemic involvement; PE poses significant risks of cerebral complications, including eclampsia and long-term cognitive impairment. This review explores the potential of neurological biomarkers—neurofilament light chain (NfL), neuron-specific enolase (NSE), S100 Calcium Binding Protein B (S100B), and tau—as indicators of cerebral injury in PE. A literature search identified studies comparing biomarker levels in preeclamptic and healthy pregnancies. Findings reveal elevated plasma levels of NfL, NSE, S100B, and Tau in PE, with NfL showing the strongest association with blood–brain barrier dysfunction, cognitive symptoms, and disease severity. Variations between plasma and cerebrospinal fluid levels suggest impaired BBB integrity rather than increased central nervous system production. Despite promising correlations, limitations include small sample sizes, lack of standardized thresholds, and limited CSF data. While NfL emerges as a particularly promising marker for risk stratification, further research is needed to validate the clinical utility of these biomarkers in routine PE management. Full article

Preeclampsia is a serious pregnancy disorder of unknown etiology. One of its cellular hallmarks is increased mitochondrial dysfunction in placental tissue. Further investigation into this aspect may help elucidate the molecular basis of preeclampsia. A total of 24 pregnant women who delivered by cesarean section participated in the study: n = 13 controls and n = 11 diagnosed with preeclampsia. Maternal blood samples were collected to assess the biochemical profile, and demographic and clinical data were recorded. Placental trophoblast samples were processed to isolate mitochondria and perform molecular biology assays. Women with preeclampsia exhibited the characteristic clinical features of the disease, along with biochemical alterations consistent with an inflammatory process. A significant decrease (73%) in mitochondrial DNA (mtDNA) copy number in trophoblastic tissue and a reduction in citrate synthase (CS) activity (−51%) in cytotrophoblast mitochondria-enriched fractions were observed in preeclampsia, indicating mitochondrial dysfunction accompanied by a loss of functional mitochondrial mass. In addition, we detected a marked decrease in MnSOD levels (−32%), together with an increase in the LC3II/LC3I ratio (47%) in cytotrophoblast mitochondria-enriched fractions, supporting the presence of mitochondrial alterations and suggesting the possible activation of mitophagy specifically in this cell type. Moreover, coenzyme Q₁₀ (CoQ₁₀) levels were elevated by 31% in trophoblastic villi. A pronounced 2.5-fold increase in CoQ₁₀ normalized to CS activity (CoQ₁₀/CS) was detected specifically in cytotrophoblasts from preeclamptic placentas. Importantly, we did not observe these alterations in the syncytiotrophoblast. In conclusion, preeclampsia is associated with mitochondrial dysfunction and increased CoQ₁₀ levels normalized to CS activity, specifically in cytotrophoblast mitochondria, with findings being consistent with a possible involvement of mitophagy in this cell type. These findings suggest that cytotrophoblast mitochondrial metabolism may be more affected in preeclampsia compared with syncytiotrophoblasts, and that CoQ₁₀ accumulation together with the possible activation of mitophagy may represent cellular defense mechanisms. Due to the limitations of the study, it should be considered exploratory and hypothesis-generating, and its results should be regarded as preliminary. Full article

Background/Objectives: Hypertensive disorders of pregnancy (HDP) remain a significant cause of maternal and perinatal morbidity worldwide. In some healthcare settings, access to angiogenic testing is limited, underscoring the need for affordable biomarkers to guide risk assessment. NT-proBNP, a marker of myocardial wall stress and cardio-renal dysfunction, may offer complementary prognostic value to the angiogenic sFlt-1/PlGF ratio. Methods: In this prospective multicenter observational study, we enrolled 180 pregnant women and categorized them into preeclampsia (PE, n = 95), non-PE HDP (gestational or chronic hypertension, n = 25), and healthy controls (n = 60). NT-proBNP and sFlt-1/PlGF levels were measured at enrollment, after 20 weeks of gestation, predominantly during the second and third trimesters. Associations with proteinuria, uric acid, creatinine, and maternal–fetal complications were examined using multivariable logistic regression adjusted for maternal age, BMI, and gestational age. Discrimination was assessed using receiver operating characteristic (ROC) curve analysis, and the incremental value of NT-proBNP beyond the sFlt-1/PlGF ratio was evaluated using ΔAUC and net reclassification improvement (NRI). Results: Median NT-proBNP levels were significantly higher in PE compared with non-PE HDP and controls (p < 0.01). NT-proBNP ≥200 pg/mL independently predicted maternal–fetal complications (adjusted OR 3.12, 95% CI 1.41–6.90, p = 0.005) and correlated with proteinuria (r = 0.47), creatinine (r = 0.43), and uric acid (r = 0.40) (all p < 0.001). sFlt-1/PlGF alone yielded an AUC of 0.84 (95% CI 0.77–0.89), while NT-proBNP alone demonstrated an AUC of 0.78 (0.71–0.84). Combining both biomarkers improved discrimination (AUC 0.88, 95% CI 0.82–0.92), with a ΔAUC of 0.04 (p = 0.02) and a continuous NRI of 0.21 (p = 0.03). The 200 pg/mL threshold for NT-proBNP achieved 80% sensitivity and 71% specificity (p < 0.001). Conclusions: NT-proBNP provides independent and complementary prognostic value to the sFlt-1/PlGF ratio in predicting maternal–fetal complications in HDP. A practical threshold of 200 pg/mL aids risk assessment, and integrating NT-proBNP into angiogenic models improves prediction. Further multicenter studies are needed to validate multimarker strategies and their cost-effectiveness. Full article

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with oxidative stress and mitochondrial dysfunction. NRF1 and NRF2 are transcription factors that regulate mitochondrial activity and antioxidant defense. This study investigated their expression patterns in placentas from preeclamptic and severe preeclamptic pregnancies by immunohistochemical and bioinformatical methods. Methods: Placentas from 40 healthy controls, 40 PE, and 40 sPE patients were analyzed by histological and immunohistochemical techniques. Protein–protein interaction networks for NRF1, NRF2, and PE-related proteins were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis performed via ShinyGO, with significance set at false discovery rate (FDR) < 0.05. Results: NRF1 expression was significantly decreased in PE and sPE groups compared to controls, with notably negative staining in syncytial knots and fibrinoid areas. Conversely, NRF2 expression significantly increased, showing intense positivity in syncytiotrophoblasts, stromal cells, and vascular structures. Pathway analysis revealed that decreased NRF1 expression was associated with glutathione metabolism, hypoxia inducible factor-1 (HIF-1) signaling, and AMP-Activated Protein Kinase (AMPK) signaling pathways. Increased NRF2 expression was associated predominantly with inflammatory and immune response pathways, including AGE-RAGE signaling and pathogen–response pathways. Conclusions: Differential expressions of NRF1 and NRF2 in preeclamptic placentas reflect distinct yet interconnected responses to oxidative stress and inflammation. These transcription factors have potential clinical relevance as biomarkers for PE severity assessment and as targets for future therapeutic interventions. Full article

Over a quarter of human pregnancies are associated with complications, including fetal growth restriction, pre-eclampsia and gestational diabetes. These are major causes of maternal and fetal morbidity and mortality, and also lead to a 3–5-fold increased risk of subsequent development of cardio-metabolic diseases. Although the mechanistic details remain elusive, a dysfunctional placenta is central to the pathophysiology of these conditions. The placenta ensures sufficient nutrient supply to the fetus without compromising maternal wellbeing. This balance is achieved by the secretion of large quantities of placental-derived peptide hormones into the maternal circulation. Consequently, the placenta is susceptible to endoplasmic reticulum (ER) stress, and we were the first to demonstrate the presence of ER stress in placentas from complicated pregnancies. The mouse placenta provides an ideal model for studying the impact of ER stress as it is composed of two distinct regions, an endocrine zone and a transport zone. Therefore, perturbation of placental endocrine function by ER stress can be generated without directly affecting its capacity for nutrient exchange. In this review, we summarise the current literature on how transgenic mouse models enhance our understanding of ER stress-mediated perturbation of placental endocrine function, and its contribution to the pathophysiology of pregnancy complications and life-long health. Full article

Background: The World Health Organization (WHO) has recently focused much attention on physical activity recommendations. Regular physical activity offers broad health benefits, reducing the risk of some chronic diseases and improving bone structure and muscle strength. Although the scientific literature provides numerous recommendations for physical activity during pregnancy and the postpartum period, there are no official recommendations for lifestyle-related physical activity. Objectives: This narrative review aimed to review the current knowledge on physical activity during pregnancy and the postpartum period, specifically focusing on lifestyle-related physical activity. The review was based on the definition of lifestyle-related physical activity proposed by Dunn et al. in 1998, which is at least 30 min of self-selected activity per day, encompassing all recreational, occupational, or household activities, as well as planned and unplanned activities that are part of daily life. Methods: A number of databases were analyzed, including PubMed, the Cochrane Library, Embase, and Web of Science. Results: The most valuable reports and recommendations regarding physical activity during the perinatal period were identified. Conclusions: Moderate physical activity during pregnancy is safe and offers benefits, such as reducing the risk of gestational diabetes, preeclampsia, and excessive weight gain, as well as improving mental health. The most common benefits of continuing physical activity after delivery include weight control, reduced risk of depression, and improved quality of life. Lifestyle-based physical activity is easier to implement and more achievable than structured exercise. Further research is needed to establish recommendations regarding lifestyle-based physical activity during the perinatal period. Full article

Objective: To investigate the impact of proteinuria severity on obstetric and neonatal outcomes and to assess the predictive value of 24 h urinary protein excretion, both alone and within a multivariable model, for adverse pregnancy outcomes. Methods: This retrospective cohort study included 203 pregnant women with proteinuria who were classified into mild (≥0.3 g/day and <3.0 g/day, n = 50), severe (≥3.0 g/day and <5.0 g/day, n = 67), and massive (≥5.0 g/day; n = 86) groups based on 24 h urine protein levels. Maternal and neonatal outcomes were compared between these groups. Correlation analysis, receiver operating characteristic (ROC) curve analysis, and multivariable logistic regression were used to evaluate the predictive value of proteinuria for obstetric complications and identification of increased risk of early delivery. The AUC values of the proteinuria-only model and the multivariable model were compared using the DeLong test, as both models were derived from the same dataset and therefore represented correlated ROC curves. Results: The incidence of obstetric complications was significantly higher in the severe (68.7%) and massive (81.4%) proteinuria groups compared with the mild group (32.0%; p < 0.001). Increasing proteinuria severity was associated with earlier gestational age at delivery, lower birth weight, and higher rates of fetal growth restriction (all p < 0.001). The 24 h proteinuria level demonstrated moderate predictive ability for obstetric complications (AUC 0.73; 95% CI 0.66–0.80). A multivariable model including nephrotic-range proteinuria (≥3 g/day) and gestational age at diagnosis showed improved discriminatory performance compared with proteinuria alone (AUC 0.81; 95% CI 0.75–0.88). The model based on continuous 24 h proteinuria yielded an AUC of 0.73 (95% CI, 0.66–0.80) for identifying pregnancies at increased risk of obstetric complications. The multivariable model showed a numerically higher AUC of 0.81 (95% CI, 0.73–0.86); however, the difference between the two AUCs was not statistically significant according to the DeLong test (z = 0.82, p = 0.41). Conclusions: The severity of maternal proteinuria is associated with a higher likelihood of adverse maternal and neonatal outcomes, and higher proteinuria levels appear to show a graded association with increasing risk. A multivariable model integrating proteinuria with key clinical parameters demonstrated moderate discriminatory ability for obstetric complications, may support a more holistic approach to risk stratification in clinical practice. Full article

Feingold syndrome (FS) is a rare congenital disorder with an autosomal dominant inheritance pattern. Two distinct subtypes are recognized based on their molecular pathology: FS type 1 (FS1) and FS type 2 (FS2). Both types share skeletal anomalies such as microcephaly, brachymesophalangia, and clinodactyly; however, gastrointestinal atresia is unique to FS1. Herein, we report a rare prenatal diagnosis of FS1 in a female fetus. The second-trimester ultrasound revealed bilateral clinodactyly and fetal microcephaly, and the subsequent molecular karyotyping identified a ~342 kb deletion at 2p24.3 encompassing the MYCN gene, confirming the diagnosis. The same deletion was detected in the father, verifying the hereditary pattern. The pregnancy was also complicated by preeclampsia and fetal growth restriction, leading to preterm caesarean delivery at 33 + 3 weeks of gestation. The neonate had microcephaly and clinodactyly but no gastrointestinal defects. In conclusion, high clinical suspicion aroused by identifying ultrasound features of FS can lead to early prenatal diagnosis via molecular karyotyping. Detecting accompanying gastrointestinal disorders that require early operation is crucial for the prognosis, genetic counseling, and prenatal management of the affected families. Full article

Background/Objectives: Vitamin D deficiency has been associated with an increased risk of adverse perinatal outcomes (APOs). This study aimed to examine whether vitamin D deficiency during the first trimester of pregnancy is linked to the development of gestational diabetes mellitus (GDM) in a Mexican population. Methods: A total of 404 pregnant women from the Biochemical and Epigenetic Origin of Overweight and Obesity (OBESO) cohort were included. Maternal vitamin D levels were measured between 11 and 14 weeks of gestation. Vitamin D deficiency was defined as a level below 20.0 ng/mL. The primary goal was to compare APOs between Group 1 (women with vitamin D deficiency) and Group 2 (women without vitamin D deficiency). Adjusted odds ratio (aOR) for APOs—including GDM, preeclampsia, preterm birth, miscarriage, cesarean section, and neonatal size—were calculated, adjusting for pregestational body mass index (BMI) and obesity, with 95% confidence interval (95% CI). Results: Vitamin D deficiency was present in 40.5% of women. Pre-pregnancy BMI and obesity were significantly higher in women with deficiency; other baseline characteristics did not differ between groups. Women with vitamin D deficiency had a higher risk of GDM (aOR 2.04, 95% CI 1.14–3.65, p = 0.01). No association was found between vitamin D deficiency and other APOs. Conclusions: The incidence of vitamin D deficiency in the first trimester was 40.5%. Early pregnancy vitamin D deficiency increases the risk of GDM among Mexican women. These findings highlight the importance of monitoring and supplementing vitamin D during pregnancy to reduce the risk of GDM. Full article

Background: Folic acid supplementation (FAS) before and in early pregnancy prevents neural tube defects, but the benefits of extending FAS to late pregnancy on pregnancy outcomes remain unclear. We aimed to investigate the associations between duration of FAS and a spectrum of pregnancy outcomes, and to determine whether the associations were modified by maternal age or pre-pregnancy body mass index (BMI). Methods: This prospective multicenter study included 15,694 singleton pregnancies. We used mixed-effects log-binomial regression models to estimate the adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHDs), pre-eclampsia, preterm birth, macrosomia, small (SGA) and large for gestational age (LGA), and the interaction effects of advanced maternal age and pre-pregnancy BMI. Results: Of 15,694 women, 4523 (28.8%) did not take FAS before or during pregnancy, 2854 (18.2%) took FAS only during peri-pregnancy, 921 (5.9%) took FAS from peri- to mid-pregnancy, and 7396 (47.1%) took it through late pregnancy. Compared with women without FAS, those supplemented until mid-pregnancy were associated with lower risks of GHDs (aRR 0.84, 95% CI 0.74, 0.96) and pre-eclampsia (aRR 0.81, 95% CI 0.67, 0.97). Supplementation until late pregnancy was associated with lower risks of preterm birth (aRR 0.67, 95% CI 0.59, 0.76), SGA (aRR 0.74, 95% CI 0.63, 0.87), and LGA (aRR 0.88, 95% CI 0.79, 0.97). Among women of advanced maternal age or with overweight/obesity, supplementation until mid-pregnancy was associated with higher risk of GDM. Conclusions: Extending FAS until mid-pregnancy is associated with lower risks of GHDs and preeclampsia, and extending it until late pregnancy is associated with lower risks of preterm birth, SGA, and LGA. However, women of advanced maternal age or with overweight/obesity should be cautious about prolonging FAS. Full article

Preeclampsia (PE) affects 2–8% of pregnancies, yet it lacks curative treatment options. Oxidative stress caused by the release of reactive oxygen and nitrogen species (ROS/RNS) in the placenta is common in abnormal placental development. It can cause downstream signaling and the formation of anti-angiogenic factors, e.g., soluble fms-like tyrosine kinase 1 (sFLT-1), leading to symptoms of PE, such as hypertension, proteinuria, and, in severe cases, eclampsia. Mitochondria-targeted antioxidants were developed to reduce oxidative stress and alleviate PE symptoms. Ten organofluorine diaryl hydrazones were designed as potential antioxidants, synthesized, and tested for their activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and oxygen radical absorbance capacity (ORAC) assays. Compounds 2, 3, 5, and 6 showed excellent antioxidant capacity in all three assays and were tested in an in vitro human trophoblast cell culture system mimicking PE in which the cells were exposed to oxidative stress inducing the release of sFLT-1. The anti-angiogenic factor sFLT-1 was greatly reduced in cells treated with antioxidants. Compounds 5 and 6 were more effective in preventing sFLT-1 release than 2 and 3. Density functional theory calculations of the electronic structures of compounds 2, 5, and 6 were conducted at the M06-2X/6-311G+(d,p) level to further understand the reactivity profile of these molecules. The electron density of delocalized bonds (EDDB(r)) was calculated to analyze the effect of delocalization on radical stabilization. Full article

Copper (Cu), zinc (Zn), and selenium (Se) play a pivotal role in pregnancy. Both a deficiency and an excess of Cu, Zn, and Se have deleterious consequences for the outcome of pregnancy. Accordingly, maintaining optimal levels of circulating Cu, Zn, and Se is critical for proper fetal growth and development. However, to our knowledge, this is the first narrative global review that not only summarizes Cu, Zn, and Se levels in maternal and cord blood but also examines their associations with multiple adverse pregnancy outcomes. Thus, this up-to-date review seeks to address these key questions. To achieve these goals, literature was collected from the past several decades from three relevant databases (PubMed, Scopus, and Cochrane Library), and rigorous exclusion and inclusion criteria were set for peer-reviewed studies that met the requirements for a final inclusion in the review analysis. In this study, data is presented on the levels of Cu, Zn, and Se in maternal and cord blood across the globe (herein used to suggest optimal maternal levels for Cu, Zn, and Se during a normal, healthy pregnancy), elemental differences between maternal and cord blood, and the fluctuations of their blood levels depending on the trimester of pregnancy. In addition, the review presents findings on the effects of Cu, Zn, and Se on birth weight and anthropometric parameters of newborns, as well as on preterm birth, preeclampsia, gestational diabetes mellitus, neural tube defects, and congenital heart defects. Full article

Pre-eclampsia affects several physiological systems, often changing the course of pregnancy and manifesting with both maternal and foetal adversities, with a higher burden in rural Sub-Saharan African settings. This study presents maternal and foetal adverse outcomes associated with pre-eclampsia at a rural tertiary hospital in the Eastern Cape Province of South Africa. A prospective analytical case-control study was conducted with 250 pregnant women planned for delivery at the study setting’s labour unit. Pregnant women with pre-eclampsia were considered cases, whereas pregnant women without pre-eclampsia were considered controls. Cases were enrolled first, followed by a matched pair of controls based on their gravidity. A consecutive sampling technique was used to recruit eligible cases and controls. Data was collected using a self-designed questionnaire followed by descriptive and inferential analysis. Adverse foetal outcomes associated with pre-eclampsia were low birth weight [Adjusted odds ratio (AOR) = 2.1, p = 0.006] and foetal distress (AOR = 2.5, p < 0.001). Maternal outcomes associated with pre-eclampsia were haemolysis, elevated liver enzymes, and low platelets syndrome (AOR = 42.7, p < 0.001), as well as preterm delivery (AOR = 3.0, p = 0.001). Early antenatal visits, continuous monitoring of pre-eclamptic pregnant women, and implementation of preventive and curative measures to reduce the possibilities of this condition and its adverse outcomes are needed. Full article