Search Results (1,109)

Pregnancies complicated by diabetes, including pregestational and gestational diabetes mellitus, are associated with increased maternal and fetal morbidity. Early identification of at-risk pregnancies is crucial for timely intervention and improved outcomes. Emerging evidence highlights the interplay of genetic predisposition, epigenetic modifications, and non-invasive biomarkers in the early detection of diabetic pregnancies. Genetic factors influencing insulin signaling, glucose metabolism, and pancreatic β-cell function may contribute to susceptibility to gestational hyperglycemia. Concurrently, epigenetic alterations, such as DNA methylation and histone modifications in maternal and placental tissues, have been linked to dysregulated metabolic pathways and adverse pregnancy outcomes. Non-invasive biomarkers, including circulating cell-free DNA and microRNAs in maternal blood, show promise for early diagnosis by offering a safer and more practical alternative to invasive testing. Integrating genetic, epigenetic, and molecular marker data could enhance risk stratification and enable personalized monitoring and management strategies. This review synthesizes current knowledge on the molecular underpinnings of diabetic pregnancies, evaluates the potential of emerging biomarkers for early diagnosis, and discusses the challenges and future perspectives for translating these findings into clinical practice. Understanding these mechanisms may pave the way for precision medicine approaches, ultimately improving maternal and neonatal outcomes in pregnancies affected by diabetes. Full article

Background/Objectives: Antepartum computerized cardiotocography (cCTG) represents an essential tool for assessing fetal well-being. This study aimed to comparatively evaluate antepartum cCTG-derived indices across high-risk pregnancies to identify distinctive fetal autonomic and reactivity profiles. Methods: A comparative analysis of antepartum cCTG parameters was conducted. The cohort included pregnancies beyond 28 weeks of pregnancy, 169 cases of hypertensive disorders of pregnancy (HDP), 146 of gestational diabetes mellitus (GDM), 86 of intrahepatic cholestasis (ICP), and 87 low-risk pregnancies as controls. Results: Baseline FHR remained within the physiological range across all groups (110–160 bpm; p > 0.05). Dynamic cCTG parameters exhibited clear pathology-dependent alterations. Short-term variability (STV) showed a stepwise decline from controls to ICP and GDM, reaching its lowest values in HDP (mean 1.08 bpm; p < 0.00001), accompanied by an increased proportion of epochs with STV < 1 bpm. Long-term variability suppression (LTV < 5 bpm) was significantly higher in GDM and HDP (p = 0.0077). Acceleration frequency decreased across all pathological groups, with the most pronounced reduction observed in HDP, whereas fetal movements were paradoxically elevated in both GDM and HDP. Total decelerations were more frequent in ICP and HDP; however, repetitive, late, prolonged, and >5 min decelerations remained rare and did not differ significantly between groups. Conclusions: HDP showed the most unfavorable cCTG profiles, consistent with impaired fetal autonomic regulation and chronic subclinical hypoxemia. GDM and ICP had moderate changes, suggesting milder adaptive responses. These findings emphasize the value of quantitative cCTG in differentiating fetal autonomic patterns in high-risk pregnancies and the importance of tailored surveillance strategies. Full article

Gestational diabetes mellitus (GDM) causes adverse effects on both mothers and offspring. This study investigated the effects of a polyherbal formulation combining Pandanus amaryllifolius root and Tectona grandis leaf extracts on maternal and fetal outcomes in streptozotocin (STZ)-induced GDM rats, compared with metformin. Pregnant rats were assigned to a non-diabetic reference group and diabetic groups, including an untreated diabetic group (negative control), a metformin-treated group (positive control), and diabetic groups treated with low, medium, or high doses of the pandan–teak formulation from gestation day 7 to 21. Medium and high doses significantly increased maternal body weight and pancreatic mass index (p < 0.05) without altering maternal glycemia or insulin levels. Fetal weight increased at medium and high doses, whereas crown–rump length increased only at the high dose. Placental index and fetal glucose levels decreased in a dose-dependent manner (p < 0.05), with no significant change in implantation loss. These findings suggest that the pandan–teak formulation may exert complementary actions that support placental–fetal glucose regulation and fetal growth while maintaining maternal glycemic stability, indicating its potential as a plant-based adjunct approach for gestational diabetes focused on fetal protection. Full article

Background/Objectives: A number of initiatives have refocused attention from obesity to adiposity-related organ dysfunction. In this prospective observational study, we examined this paradigm postpartum. Methods: At King’s College Hospital, London, UK, we invited for review by six months postpartum, consecutive women with GDM (N = 1442, September 2023–August 2025) and without GDM (N = 646, January 2025–August 2025). Those with excess adiposity (BMI ≥ 30 kg/m² and waist-to-height ratio > 0.5) were assessed for organ dysfunction, using criteria from a recent Commission: anovulation, metabolism or renal clusters, raised blood pressure, or elevated end-diastolic left ventricular filling pressure. Multiple regression determined predictors of adiposity-related organ dysfunction, the prevalence of which was calculated as a range (highest estimate: absolute organ dysfunction prevalence; lowest estimate: adiposity-adjusted, as highest estimate minus prevalence of organ dysfunction in women without excess adiposity). Results: Of those invited for review, 1086/1442 (75.3%) GDM and 562/646 (87.0%) non-GDM women attended, at median 5.8 months after birth (interquartile range 4.8–6.7). Excess adiposity was observed in 385/1086 (35.5%) GDM and 117/562 (20.8%) non-GDM women, among whom organ dysfunction was seen in 61.0% GDM (235/385), 51.3% non-GDM (60/117). 35.9% (408/1137) of women without excess adiposity. Organ dysfunction attributable to excess adiposity was estimated to be 22.9% (58.8% minus 35.9%), and was poorly predicted by the multivariable model (AUC 0.64, 95%CI 0.60–0.69). Conclusions: Among women with prior GDM, organ dysfunction attributable to excess adiposity affects at least 20% of those with excess adiposity postpartum, and is not currently predictable. Full article

Background/Objectives: To construct and compare multivariable prediction models for the early prediction of large-for-gestational-age (LGA) neonates, using ultrasound biometry and maternal characteristics. Methods: This retrospective cohort study analyzed data from singleton pregnancies that underwent routine ultrasound examinations at 30⁺⁰–34⁺⁰ weeks of gestation. Ultrasound parameters included fetal abdominal circumference (AC), head circumference (HC), femur length (FL), HC-to-AC ratio, mean uterine artery pulsatility index (mUtA-PI), and presence of polyhydramnios. LGA neonates were defined as those having a birthweight > 90th percentile. Logistic regression was used to evaluate associations between ultrasound markers and LGA after adjusting for the following maternal and pregnancy-related covariates: maternal age, body mass index, parity, gestational diabetes mellitus (GDM), pre-existing diabetes, previous cesarean section (PCS), assisted reproductive technology (ART) use, smoking, hypothyroidism, and chronic hypertension. Associations were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Three prognostic models were developed utilizing the following predictors: (i) biometric ultrasound measurements including AC, HC-to-AC ratio, FL, UtA-PI, and polyhydramnios (Model 1), (ii) a combination of biometric ultrasound measurements and clinical–maternal data (Model 2), and (iii) only the estimated fetal weight (EFW) (Model 3). Results: In total, 3808 singleton pregnancies were included in the analyses. The multivariable analysis revealed that AC (aOR 1.07, 95% CI [1.06, 1.08]), HC to AC (aOR 1.01, 95% CI [1.006, 1.01]), FL (aOR 1.01, 95% CI [1.009, 1.01]), and the presence of polyhydramnios (aOR 4.97, 95% CI [0.7, 58.8]) were associated with an increased risk of LGA, while a higher mUtA-PI was associated with a reduced risk (aOR 0.98, 95% CI [0.98, 0.99]). Maternal parameters, such as GDM, pre-existing diabetes, elevated pre-pregnancy BMI, absence of uterine artery notching, mUtA-PI, and multiparity, were significantly higher in the LGA group. Both models 1 and 2 showed similar performance (AUCs: 84.7% and 85.3%, respectively) and outperformed model 3 (AUC: 77.5%). Bootstrap and temporal validation indicated minimal overfitting and stable model performance, while decision curve analysis supported potential clinical utility. Conclusions: Models using biometric and Doppler ultrasound at 30–34 weeks demonstrated good discriminative ability for predicting LGA neonates, with an AUC up to 84.7%. Adding maternal characteristics did not significantly improve performance, while the biometric model performed better than EFW alone. Sensitivity at conventional thresholds was low but increased substantially when lower probability cut-offs were applied, illustrating the model’s threshold-dependent flexibility for early risk stratification in different clinical screening needs. Although decision curve analysis was performed to explore potential clinical utility, external validation and prospective assessment in clinical settings are still needed to confirm generalizability and to determine optimal decision thresholds for clinical application. Full article

Metformin, the most widely prescribed oral antihyperglycemic agent, is established as the first-line therapy for type 2 diabetes mellitus (T2DM) owing to its efficacy, affordability, and safety. Increasing evidence indicates that its benefits extend beyond glycemic control, encompassing cardiovascular protection and diabetes prevention in individuals at elevated cardiometabolic risk. Mechanistic studies demonstrate that metformin exerts pleiotropic effects through activation of AMP-activated protein kinase, modulation of the gut microbiota, inhibition of pro-inflammatory and oxidative stress pathways, and improvements in endothelial function, lipid metabolism, and insulin sensitivity. These actions address core drivers of atherosclerosis and metabolic dysfunction, many of which occur independently of glucose lowering. In patients with T2DM, the cardiovascular benefits of metformin are well recognized, including reductions in all-cause mortality and cardiovascular events. In individuals without diabetes but at high cardiovascular risk—such as those with prediabetes, obesity, or metabolic syndrome—evidence is more limited, as most data are derived from subgroup analyses or trials with surrogate endpoints. Nonetheless, consistent signals suggest that metformin may delay the progression from prediabetes to overt diabetes and potentially confer vascular protection, particularly in carefully selected high-risk populations. Clinical trials and meta-analyses have demonstrated that metformin reduces incident diabetes by approximately one quarter in high-risk adults, with stronger effects observed in younger, overweight individuals, women with prior gestational diabetes, and those treated for longer durations. However, uncertainties remain regarding its long-term cost-effectiveness, optimal dosing strategies, and cardiovascular benefits in non-diabetic populations. The ongoing VA-IMPACT trial (NCT02915198) is expected to clarify whether metformin reduces major cardiovascular events in prediabetic patients with atherosclerotic disease. Taken together, metformin represents more than an antidiabetic drug. Its pleiotropic mechanisms, favorable safety profile, and low cost support its potential integration into broader cardiometabolic prevention strategies, including primary prevention. Expanding its role beyond diabetes management may offer a cost-effective, widely accessible intervention with significant public health impact. Full article

Background: Gestational diabetes mellitus (GDM) is a frequent pregnancy pathology with poor maternal and fetal outcomes and risk of type 2 diabetes in later life. Despite known risk factors, such as obesity, age, and familial history, new data suggest that environmental exposure to agents, such as pesticides, can play a role in the etiogenesis of GDM. Objective: The epidemiologic, experimental, and mechanistic evidence between pesticide exposure and GDM risk is summarized here, and we concentrate on recent research (2000–2025). Methods: We conducted a literature search in PubMed, Embase, and the Cochrane Library for studies published from January 2000 to December 2025 using combinations of the terms “fertilizers”, “herbicides”, and “pesticides” with “diabetes mellitus” and “gestational diabetes”. After deduplication, 12 unique studies met inclusion criteria for qualitative synthesis (GDM endpoint or pregnancy glycemia with pesticide exposure). Results: Occupational and agricultural exposure to pesticides during first pregnancy was determined to be associated with a significantly increased risk of GDM through various epidemiologic studies. New studies have implicated new classes of pesticides, including pyrethroids and neonicotinoids, with higher GDM risk with first-trimester exposure. Experimental studies suggest that pesticides provide potential endocrine-disrupting chemicals that can induce insulin resistance through disruption of hormonal signaling, oxidative stress, inflammation, β-cell toxicity, and epigenetic modifications. However, significant limitations exist. Most of the evidence is observational, measurement of exposure is often indirect, and confounding factors are difficult to exclude. Notably, low dietary and residential exposure is not well studied, and dose–response relationships are undefined. Conclusions: New data indicate that pesticide exposure during early pregnancy and occupational exposure may increase the risk of GDM. Prospective cohort studies using biomonitoring, chemical mixture exposure, and geographic variation in pesticide exposure should be the focus of future research. Due to potential public health implications, preventive strategies to ensure the quality of nutrition and to reduce maternal exposure to pesticides during pregnancy are rational. Full article

Gestational diabetes mellitus (GDM) has witnessed a persistent rise in the prevalence over the past few decades, imposing a substantial burden on global health and economies. GDM exerts both short-term and long-term effects on neuropsychiatric systems of the mothers and their progeny. This review catalogs the neurodevelopmental and neuropsychiatric disorders in GDM women and their offspring and summarizes the possible relationships as well as the underlying mechanisms, which would enhance our understanding of the neuropsychiatric disorders related to GDM, offering information on personalized strategies for patients. Full article

Exosomes are nanoscale extracellular vesicles that mediate intercellular communication by transporting microRNAs, proteins, and lipids. Generated through Endosomal Sorting Complex Required for Transport (ESCRT)-dependent mechanisms or ESCRT-independent pathways, exosomes are released when multivesicular bodies fuse with the plasma membrane. The ESCRT-dependent pathway involves sequential protein complexes (ESCRT-0, I, II, III) that recognize and sort ubiquitinated cargo, induce membrane budding, and facilitate vesicle scission. In contrast, the ESCRT-independent pathway relies on membrane lipids such as ceramide and proteins like tetraspanins (CD9, CD63, CD81) to promote vesicle formation without ESCRT machinery. Furthermore, post-translational modifications, including ubiquitination, sumoylation, and phosphorylation, further serve as molecular switches, modulating the affinity of ESCRT complexes or cargo proteins for membrane domains and affecting ILV formation rates. In reproductive medicine, exosomes regulate oocyte maturation, embryo–endometrial crosstalk, placental development, and maternal–fetal communication. Altered exosomal signaling contributes to obstetric complications, including preeclampsia, gestational diabetes mellitus, and preterm birth, whereas distinct exosomal miRNA signatures serve as potential diagnostic biomarkers. In gynecology, dysregulated exosomes are implicated in endometriosis, polycystic ovary syndrome, premature ovarian insufficiency, and gynecological malignancies. In contrast, mesenchymal stem cell-derived exosomes show therapeutic promise in restoring ovarian function and enhancing fertility outcomes. The distinctive molecular profiles of circulating exosomes enable minimally invasive diagnosis, while their biocompatibility and ability to cross biological barriers position them as vehicles for targeted drug delivery. Characterization of accessible data provides non-invasive opportunities for disease monitoring. However, clinical translation faces challenges, including standardization of isolation protocols, establishment of reference ranges for biomarkers, and optimization of therapeutic dosing. This review summarizes exosome biogenesis, characterization methods, physiological functions, and clinical applications in obstetrics and gynecology, with an emphasis on their diagnostic and therapeutic potential. Future directions include large-scale biomarker validation studies, engineering approaches to enhance exosome targeting, and integration with precision medicine platforms to advance personalized reproductive healthcare. Full article

Background: Gestational diabetes mellitus (GDM) is one of the most common metabolic complications of pregnancy, and its prevalence continues to rise worldwide. Dietary management is the cornerstone of therapy, yet adherence may impose a substantial everyday burden. This study aimed to assess perceived burden and practical challenges related to following a diabetic diet in women with GDM. Methods: A cross-sectional anonymous online questionnaire study was conducted among 109 women with a current or past diagnosis of GDM within the previous five years. The survey addressed self-reported difficulties in maintaining normal blood glucose levels, adherence to a diabetic diet, perceived increases in grocery expenses, time required for meal preparation, dietary preferences, and family attitudes toward the diet. Associations between categorical variables were analyzed using contingency tables and the contingency coefficient. Results: Women with insulin-treated GDM (GDM2) reported more difficulties maintaining normal blood glucose levels than women treated with diet and physical activity alone (GDM1) (p = 0.014). Educational level was associated with perceived financial burden (p = 0.013) and meal preparation time (p = 0.003). These patterns likely reflect both differences in economic resources and the extent of dietary changes undertaken, rather than uniform differences in nutritional awareness. Pregnancy status was associated with dietary preferences, as non-pregnant respondents more often reported liking diabetic-diet meals than pregnant respondents (p = 0.037). Overall, 53.2% of respondents reported that a diabetic diet made daily functioning more difficult, mainly due to increased time and financial demands. Conclusions: Dietary management of GDM is associated with a meaningful perceived burden, especially among women requiring insulin therapy and those facing financial and time constraints. Understanding these subjective challenges may support more individualized dietary counseling and patient-centered care. 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

Gestational diabetes mellitus (GDM) is a multifactorial metabolic disorder arising from impaired insulin sensitivity and altered maternal–fetal energy regulation. Beyond classical mechanisms involving β-cell dysfunction and pregnancy-induced insulin resistance, emerging evidence suggests a bidirectional interaction between the maternal gut microbiota and the placenta, forming a dynamic placenta–gut axis. Microbial dysbiosis alters levels of metabolites, inflammatory mediators, and bile acids, which influence placental signaling, trophoblast metabolism, immune activation, and nutrient transport. Conversely, the placenta secretes hormones, cytokines, lipids, and exosomal miRNAs that shape maternal metabolism and potentially modulate the gut microbiota. This review synthesizes current mechanistic insights underlying the placenta–gut microbiota axis in GDM, describes immune and metabolic crosstalk, and highlights therapeutic opportunities targeting this inter-organ communication system. Addressing these interactions may advance precision strategies for managing GDM and improving outcomes across generations. 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

Background: Early prediction of gestational diabetes mellitus (GDM) remains a major clinical challenge, and the current oral glucose tolerance test (OGTT) is time-consuming and inconvenient for clinical routine. This study aimed to develop a novel predictive model for postprandial hyperglycemia GDM (pp-GDM) and postprandial glucose elevation using fasting serological and metabolic profiles. Method: We used High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) to analyze fasting plasma amino acid profiles at 24–28 weeks of gestation for 60 pp-GDM patients and 120 controls. Binary logistic regression model was constructed to identify potential biomarkers for pp-GDM prediction. Results: By incorporating amino acid indicators such as isoleucine, phenylalanine, threonine, and aspartate into the predictive model alongside traditional predictors (including BMI at sampling, fasting insulin, glycated hemoglobin, and uric acid), the overall predictive performance was significantly improved from 78.2% to 91.1%. A clinically practical nomogram for risk assessment was subsequently developed. Conclusions: This fasting metabolite-based model provides a reliable tool for early prediction of pp-GDM and postprandial hyperglycemia, which may reduce the need for OGTT and facilitate timely clinical decision making. 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