Search Results (1,022)

Aim: Gestational diabetes mellitus (GDM) is defined as glucose intolerance diagnosed during pregnancy and can lead to significant health problems for both the mother and the baby. We aimed to compare e-health literacy levels according to oral glucose tolerance test (OGTT) status at study enrollment and to examine the association between e-health literacy and OGTT status. Materials and Methods: The study included 45 pregnant women classified as OGTT-tested and 122 classified as OGTT-untested based on their OGTT status at study enrollment. All participants completed a sociodemographic data form and the e-health Literacy Scale (eHEALS). Results: A total of 167 pregnant women were included in the study; 45 (26.9%) had undergone an OGTT during their current pregnancy, while 122 (73.1%) had not. The mean total score on the eHEALS was 24.71 ± 8.58. No significant difference in eHEALS scores was observed between the OGTT-tested and OGTT-untested groups (25.04 ± 8.20 vs. 24.58 ± 8.75; Hodges–Lehmann median difference = 0.00, 95% CI: −3.00 to 4.00; p = 0.788; r = 0.027). In contrast, the proportion of women who had undergone an OGTT in a previous pregnancy was higher among those who underwent an OGTT in their current pregnancy (p < 0.001). eHEALS scores showed significant differences by age group (p = 0.019), education level (p < 0.001), and trimester (p = 0.014); the highest scores were observed in the ≥35 age group and among university graduates. eHEALS scores showed a positive correlation with age (rho = 0.240; p = 0.002) and a negative correlation with gestational week (rho = −0.225; p = 0.004). In the multiple linear regression model, having a college degree (B = 4.079; 95% CI: 0.244–7.915; p = 0.037) and trusting health information on the internet (B = 3.466; 95% CI: 0.421–6.511; p = 0.026) were independently associated with higher e-health literacy scores. Among the 45 pregnant women who underwent OGTT, 14 (31.1%) were diagnosed with GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. In an exploratory subgroup analysis restricted to participants who underwent OGTT, eHEALS scores were higher among women diagnosed with GDM than among those without GDM (p = 0.042). Conclusions: In conclusion, in this sample, the level of e-health literacy did not differ significantly according to OGTT status at study enrollment. Full article

Background: Maternal overweight, obesity, and inappropriate gestational weight gain (GWG) are increasingly recognized as major contributors to adverse pregnancy outcomes worldwide. Elevated pre-pregnancy body mass index (BMI) is associated with gestational diabetes mellitus (GDM), hypertensive disorders, cesarean delivery, fetal overgrowth, and long-term cardiometabolic risks for both mother and child. Regional contemporary data from Bulgaria remain limited. Objective: The objective of this study was to evaluate trends in maternal obesity and gestational weight gain among pregnant women in Southeastern Bulgaria between 2021 and 2025, using a regional cohort from Burgas, and to assess associations with maternal and neonatal outcomes. Methods: This retrospective cohort study included 1176 singleton pregnancies registered for antenatal follow-up at MC Prime Clinic–Dr. Kirovakov Ltd., Burgas, Bulgaria, between January 2021 and December 2025. Women were classified according to World Health Organization BMI categories as underweight, normal weight, overweight, and obese. Gestational weight gain was categorized as below, within, or above Institute of Medicine recommendations. Maternal and neonatal outcomes were analyzed using comparative statistics and multivariable logistic regression. Results: The mean maternal age was 30.8 ± 5.4 years, and the mean pre-pregnancy BMI was 25.1 ± 4.8 kg/m². BMI distribution was: underweight 7.6%, normal weight 49.8%, overweight 27.9%, and obesity 14.7%. Overall, 42.6% of women entered pregnancy overweight or obese. Mean total GWG was 13.2 ± 5.6 kg. Excessive GWG occurred in 39.0% of women, while only 39.6% remained within recommended ranges. Excessive GWG was significantly more common among obese women (52.8%) than among women with normal BMI (34.7%, p < 0.001). Compared with women of normal BMI, obese women had significantly higher rates of gestational diabetes mellitus (16.7% vs. 5.8%), hypertensive disorders (12.9% vs. 4.2%), preeclampsia (8.4% vs. 2.1%), cesarean delivery (47.4% vs. 28.6%), macrosomia (14.5% vs. 6.1%), and preterm birth (10.7% vs. 6.9%) (all p < 0.05). In multivariable analysis, maternal obesity independently predicted GDM (aOR 2.94, 95% CI 1.82–4.73), preeclampsia (aOR 3.18, 95% CI 1.87–5.39), cesarean delivery (aOR 2.11, 95% CI 1.42–3.14), macrosomia (aOR 2.46, 95% CI 1.51–4.01), and preterm birth (aOR 1.67, 95% CI 1.02–2.74). Conclusions: Maternal obesity and excessive gestational weight gain were highly prevalent among pregnant women in Southeastern Bulgaria during 2021–2025 and were strongly associated with adverse maternal and neonatal outcomes. These findings support the need for preconception counseling, individualized antenatal weight management, and targeted regional public health strategies. Full article

Background: Polyhydramnios is associated with adverse perinatal outcomes and is commonly assessed using either the amniotic fluid index (AFI) or the maximal vertical pocket (MVP). Although both methods are accepted in clinical practice, they frequently classify the same pregnancy differently, and their relative ability to predict adverse neonatal outcomes remains uncertain. Methods: We conducted a retrospective cohort study of pregnancies delivered at a tertiary university medical center between 2010 and 2025. Pregnancies with an AFI or MVP measurement within two weeks before delivery were eligible. Pregnancies complicated by diabetes mellitus or major fetal anomalies were excluded. Polyhydramnios severity was classified separately according to AFI and MVP criteria. The primary outcome was a composite of severe neonatal morbidity including neonatal intensive care unit admission, umbilical artery pH < 7.1, 5 min Apgar score < 7, or perinatal death. Separate multivariable logistic regression models were constructed for AFI- and MVP-based severity classifications. Results: Among 32,928 pregnancies, 3146 (9.6%) had polyhydramnios. Moderate-to-severe polyhydramnios defined by MVP was independently associated with severe neonatal morbidity (adjusted odds ratio [aOR] 2.47, 95% confidence interval [CI] 1.57–3.90; p < 0.001), whereas AFI-based severity classification was not (aOR 1.44, 95% CI 0.98–2.12; p = 0.07). Severe neonatal morbidity increased progressively with increasing MVP measurements. Mild polyhydramnios, regardless of the measurement method, was not associated with increased neonatal morbidity. Similar findings were observed in sensitivity analyses. Conclusions: MVP-based severity classification identified pregnancies at increased risk of severe neonatal morbidity, whereas AFI-based classification did not, at their conventional thresholds. These findings suggest that MVP may provide better risk stratification in pregnancies complicated by polyhydramnios and support prospective studies to validate its role in clinical management. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and requires sustained patient engagement to achieve optimal maternal and neonatal outcomes. This narrative review synthesized current evidence on patient engagement strategies and developed clinical principles for implementing patient-centered care across the GDM care continuum. Methods: A domain-based narrative review was conducted using the Consensus literature search platform. A total of 5359 records were identified. After multi-phase screening for relevance and eligibility, 37 studies, including systematic reviews, randomized controlled trials, observational studies, and qualitative research, were included. Evidence was synthesized across four domains: universal screening and linkage to care, whole-person assessment, digital patient engagement, and postpartum transition. Results: Universal screening consistently detected more women with GDM than risk-based approaches, although greater detection alone did not consistently improve maternal or neonatal outcomes. Evidence supported structured patient education, culturally responsive communication, self-management support, and active clinician feedback as key components of effective engagement. Digital health interventions, including telehealth, mobile applications, and remote monitoring, improved adherence, self-management, patient satisfaction, and, in many studies, glycemic control when integrated with clinician oversight. Postpartum follow-up remained a persistent gap despite evidence supporting reminder systems and coordinated care transitions. These findings informed a stepped clinical care pathway tailored to low-resource community health settings. Conclusions: Current evidence supports several components of patient-centered GDM care that informed a proposed stepped clinical care pathway integrating early identification, whole-person assessment, structured education, self-management support, digital engagement, and coordinated postpartum care. Many recommended strategies can be implemented using existing personnel and low-cost digital technologies, although additional implementation research is needed to evaluate culturally tailored interventions and long-term effectiveness in underserved populations. Full article

Background/Objectives: Antiphospholipid antibodies (aPL) comprise anticardiolipin antibodies (aCL), antibodies against β2 glycoprotein I (anti-β2GPI) and lupus anticoagulant (LA). LA is an established risk factor for thrombosis and pregnancy morbidity in the general population. In people with type 1 diabetes (T1D), aPL have been proposed as potential predictors of microvascular and macrovascular diabetes-related complications. The aim of the present prospective, observational study was to investigate the prevalence of aPL in a well-defined cohort of adults presenting with uncomplicated T1D compared with healthy controls. In addition, we prospectively examined whether aPL titers or positivity were potentially associated with the subsequent development of diabetes-related complications. Methods: Two hundred (200) adults with T1D and without microvascular or macrovascular complications participated (mean age, 37.9 ± 10.6 years; mean diabetes duration, 21.00 ± 9.20 years). We also included 200 age- and sex-matched healthy controls (mean age, 37.7 ± 10.1 years) without diabetes mellitus or other autoimmune diseases. The aPL panel, including aCL ΙgG/IgM, anti- β2GPI IgG/IgM, and LA, was assessed using standardized laboratory methods. Participants with T1D were re-evaluated after a mean follow-up of 7.6 years. Results: Titers of aCL IgG/IgM and anti-β2GPI IgG, as well as positivity of aCL-IgG and aCL-IgM, were higher in participants with T1D compared with healthy controls, whereas LA positivity was very low in both groups. In the T1D group, aCL-IgG titers significantly correlated with age and diabetes duration. Neither aCL-IgG titers nor positivity was associated with the development of microvascular or macrovascular complications or with all-cause mortality during follow-up. Conclusions: In adults with long-standing, uncomplicated T1D, most aPL titers and positivity rates were higher than those observed in healthy controls. However, aCL-IgG titers and positivity were not associated with the subsequent development of diabetes-related complications. Larger prospective studies are required to determine whether aPL have predictive value for diabetes-related complications and to identify subgroups of people with T1D who may benefit from aPL testing. Full article

Background/Objectives: Congenital uterine anomalies (CUAs) are associated with adverse pregnancy outcomes, but large-scale data, particularly in Asian populations, remain limited. We evaluated obstetric and neonatal outcomes in women with CUAs using a large national Korean cohort. Methods: This population-based retrospective cohort study used the Korean National Health Insurance Service database and included 878,000 singleton deliveries between 2018 and 2023. CUAs were identified using International Classification of Disease, 10th Revision (ICD-10) codes and categorized as double, septate, bicornuate, or unicornuate uterus. Outcomes were compared with women without CUA using multivariable logistic regression adjusted for maternal age, parity, chronic hypertension, and pregestational diabetes mellitus. Results: CUAs were identified in 6038 women (0.68%), most commonly double uterus. Risks were higher for Cesarean delivery (adjusted odds ratio [aOR] 2.57, 95% confident interval [CI] 2.38–2.77), breech presentation (6.42, 5.91–6.99), placenta previa (1.79, 1.45–2.22), and placental abruption (3.01, 2.26–4.01). Neonates were more likely to be preterm (2.43, 2.10–2.80), small for gestational age (1.90, 1.70–2.10), and to experience respiratory distress syndrome (2.04, 1.63–2.55) and intraventricular hemorrhage (3.04, 2.00–4.62). Conclusions: CUAs are associated with increased risks of adverse obstetric and neonatal outcomes, with subtype-specific variations, warranting tailored prenatal counseling and management. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a heterogeneous metabolic disorder characterized by impaired glucose regulation and insulin resistance. Tetranectin is a circulating protein implicated in metabolic regulation and diabetes-related dysfunction; however, serum tetranectin levels have not previously been investigated in women with GDM. This study aimed to compare serum tetranectin levels between women with GDM and normoglycemic pregnant controls and to evaluate their associations with metabolic parameters and discriminatory performance for GDM. Methods: This prospective case–control study included 89 pregnant women recruited at the Department of Obstetrics and Gynecology, Antalya Education and Research Hospital, between January 2023 and March 2025, comprising 45 women with GDM and 44 normoglycemic controls. GDM was diagnosed using a 75 g oral glucose tolerance test. Serum tetranectin levels were measured using a commercially available enzyme-linked immunosorbent assay. Clinical, obstetric, metabolic, and laboratory parameters were compared between groups. Correlations between serum tetranectin and metabolic parameters were assessed using Spearman’s correlation analysis. Binary logistic regression was performed to evaluate the independent association between serum tetranectin and GDM. Receiver operating characteristic curve analysis was used to assess discriminatory performance. Results: No statistically significant differences were observed in baseline maternal and obstetric characteristics between the groups. Serum tetranectin levels were significantly higher in women with GDM than in normoglycemic controls (155.42 [147.99–181.36] ng/mL vs. 103.82 [66.89–159.76] ng/mL, p < 0.001). Serum tetranectin was positively correlated with HbA1c (ρ = 0.431, p < 0.001), fasting glucose (ρ = 0.350, p < 0.001), 2 h OGTT glucose (ρ = 0.277, p = 0.009), body weight (ρ = 0.270, p = 0.011), HOMA-IR (ρ = 0.246, p = 0.024), triglyceride levels (ρ = 0.243, p = 0.047), diastolic blood pressure (ρ = 0.241, p = 0.049), and body mass index (ρ = 0.224, p = 0.034). After Bonferroni correction for multiple comparisons, only the correlations with HbA1c and fasting glucose remained statistically significant. In binary logistic regression analysis, each 10 ng/mL increase in serum tetranectin was associated with higher odds of GDM in both crude and adjusted models. After adjustment for maternal age, gestational age at sampling, and body mass index, serum tetranectin remained independently associated with GDM (OR: 1.17, 95% CI: 1.06–1.28, p = 0.001). Receiver operating characteristic analysis demonstrated moderate discriminatory performance, with an AUC of 0.747 (95% CI: 0.635–0.860, p < 0.001). The optimal cut-off value was 124.59 ng/mL, yielding 95.6% sensitivity (95% CI: 84.9–99.5%) and 63.6% specificity (95% CI: 47.8–77.6%). Conclusions: Serum tetranectin levels were significantly elevated in women with GDM and remained independently associated with GDM status after adjustment for maternal age, gestational age at sampling, and body mass index. Serum tetranectin showed associations with several metabolic parameters; however, after multiple-testing correction, only fasting glucose and HbA1c remained significantly correlated with TN. Although its discriminatory performance was moderate, serum tetranectin may represent a biologically plausible circulating biomarker associated with the metabolic environment of GDM. Larger longitudinal studies are needed to validate these findings and clarify the mechanistic role of tetranectin in GDM. Full article

Background/Objectives: Umbilical artery thrombosis (UAT) is a rare but potentially catastrophic obstetric complication associated with a high risk of adverse perinatal outcomes. However, clinically applicable risk stratification tools for pregnancies complicated by UAT remain limited. Therefore, this study aimed to develop and validate a multivariable clinical prediction model integrating maternal clinical characteristics, fetal characteristics, and Doppler-derived hemodynamic parameters for fetuses with UAT. The model may facilitate early risk stratification and support individualized prenatal management and clinical decision-making. Methods: This retrospective study included 114 fetuses with UAT at the Women and Children’s Hospital of Chongqing Medical University between January 2017 and January 2025. Candidate predictors were predefined based on previous literature, clinical knowledge, and their potential associations with adverse pregnancy outcomes in UAT, encompassing maternal characteristics, UAT-related factors, Doppler-derived hemodynamic parameters, and relevant clinical factors. Predictors were selected using LASSO with 10-fold cross-validation and entered into multivariable logistic regression to construct a nomogram. Model discrimination, calibration, and clinical utility were assessed using AUC, calibration plots, and decision curve analysis, respectively. The optimal cutoff was determined by the maximum Youden index. Bootstrap resampling was used for internal validation and generalizability assessment. Results: Of the 114 fetuses, 57 (50.0%) experienced adverse pregnancy outcomes. The final nomogram incorporated maternal age, umbilical artery pulsatility index (UA-PI), ductus venosus pulsatility index (DV-PIV), uterine artery pulsatility index (UtA-PI), gravidity, diabetes mellitus, fetal growth restriction (FGR), and UAT laterality. Higher UA-PI (OR, 7.15; 95% CI, 1.01–50.57), higher DV-PIV (OR, 13.18; 95% CI, 2.34–74.41), and FGR (OR, 7.53; 95% CI, 1.77–31.97) were associated with increased odds of adverse outcomes, while UAT laterality showed a borderline association (OR, 2.61; 95% CI, 1.00–6.81). The nomogram achieved an AUC of 0.791 (95% CI, 0.706–0.876), with 70.2% sensitivity and 78.9% specificity at the optimal cutoff. Bootstrap calibration showed a mean absolute error of 0.042. Decision curve analysis demonstrated a positive net benefit across threshold probabilities of 11–92%. Conclusions: This study establishes an internally validated model for predicting adverse perinatal outcomes in fetuses with UAT using clinical characteristics and gestational age-adjusted Doppler hemodynamic parameters available at the time of diagnosis. The model may provide a basis for risk stratification and individualized antenatal surveillance. Full article

Background: Periodontal disease has been increasingly associated with several systemic conditions, including diabetes mellitus. During pregnancy, both periodontitis and diabetes mellitus—including gestational and pre-existing forms (type 1 and type 2)—share common inflammatory and metabolic pathways that may influence maternal and neonatal outcomes. However, the consistency and strength of this association remain under debate. Objective: Our objective was to synthesize the available evidence from systematic reviews and meta-analyses on the association between maternal periodontal disease and diabetes mellitus during pregnancy, as well as its relationship with adverse pregnancy outcomes. Methods: An overview of systematic reviews was conducted following PRISMA recommendations. A comprehensive search was performed in PubMed, Scopus, Web of Science, and Cochrane CENTRAL from inception to the search date. A total of 161 records were identified, with 23 articles assessed in full text. Finally, nine systematic reviews were included, seven of which incorporated meta-analyses. Methodological quality was evaluated using AMSTAR 2, and risk of bias was assessed with ROBIS. Due to heterogeneity, a narrative synthesis was conducted. The degree of overlap among reviews was quantified using the corrected covered area (CCA). Results: The evidence consistently suggests a positive association between periodontal disease and diabetes mellitus during pregnancy, with increased risk reported in multiple meta-analyses, particularly for gestational diabetes mellitus. Periodontitis was also associated with adverse pregnancy outcomes, including preeclampsia, preterm birth, and low birth weight, although findings were not entirely homogeneous. The methodological quality of the included reviews was variable, predominantly low or critically low. A high level of overlap among reviews was observed (CCA = 15.2%). Conclusions: Current evidence supports an association between maternal periodontal disease, diabetes mellitus during pregnancy, and adverse maternal-fetal outcomes. However, these findings should be interpreted with caution due to methodological limitations and study overlap. Periodontal assessment in prenatal care and oral health education may be preventive strategies. Further studies are needed to clarify causality and evaluate these interventions. Full article

Background/Objectives: Maternal obesity is associated with an increased risk of adverse maternal and neonatal outcomes. This study evaluated whether participation in a multidisciplinary antenatal care pathway improved pregnancy outcomes compared with routine clinical practice in women with pre-pregnancy obesity. Methods: 711 women of reproductive age with preconception body mass index (BMI) ≥ 30 kg/m² were identified from medical records collected between 2010 and 2023: 233 women were managed according to the multidisciplinary clinical pathway (pathway group), and 478 served as historical controls, followed at the same unit before pathway implementation. Age, BMI, gestational diabetes frequency, weight gain during pregnancy, gestational hypertension, preeclampsia/eclampsia, time and mode of delivery, birthweight, macrosomia, large for gestational age, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress, fetal morbidity, and congenital anomalies were collected. Fasting plasma glucose, glycated hemoglobin, plasma glucose values under oral glucose tolerance test, plasma cholesterol and triglyceride levels were also evaluated. Results: The first evaluation occurred significantly earlier in the pathway group than in controls. Only about half of the women in the pathway group developed gestational diabetes mellitus (GDM) during pregnancy compared with 84% of controls (47% vs. 84%, p < 0.001), a difference partly explained by a referral bias in the control group, where women were referred after GDM screening rather than on the basis of obesity alone. As for maternal complications, the frequency of hypertension, eclampsia, and preeclampsia was similar in the two groups. As for fetal outcomes, pathway group women with respect to control showed a significantly lower frequency of preterm birth (5% vs. 11%, p = 0.0275), fetal morbidity (2% vs. 6%, p = 0.0377) and a tendency to lower frequency of macrosomia (7% vs. 12%, p = 0.0677), large for gestational age (19% vs. 26%, p = 0.116) and small for gestational age babies (5% vs. 7%, p = 0.50). Conclusions: This study shows that a multidisciplinary antenatal clinical approach was associated with a reduction in some adverse maternal–fetal outcomes related to pregnancy complicated by obesity, despite a less favorable baseline risk profile in the pathway group. Preconception counseling starting before pregnancy may represent an even more effective strategy, and efforts must be made in this direction. Full article

Successful pregnancy depends on precise placental development, where trophoblast differentiation, syncytialization, invasion, and adaptation to metabolic stress are critical. Autophagy, a lysosome-mediated degradation pathway, has emerged as an important regulator of cellular homeostasis, yet its integrated role in trophoblast fate and functions has not been comprehensively summarised. This review synthesises current evidence on autophagy’s functions throughout placentation, from trophoblast differentiation to syncytialization and extravillous trophoblast invasion. We examine how autophagy enables cellular remodelling during differentiation, supports metabolic adaptation under hypoxia and nutrient stress, and maintains mitochondrial quality control through selective mitophagy. Autophagy is essential for syncytiotrophoblast formation via endoplasmic reticulum stress-coordinated activation and p53 downregulation. However, its effects on trophoblast invasion are context-dependent, influenced by oxygen tension, autophagic flux completeness, and differentiation state, which can potentially be shaped by parent-offspring genetic conflicts through genomic imprinting. Both excessive and insufficient autophagy contribute to pregnancy complications, including pre-eclampsia, foetal growth restriction, gestational diabetes mellitus, preterm birth, recurrent spontaneous abortion and obstetric antiphospholipid syndrome through distinct molecular mechanisms. Autophagy functions as a dynamically tuned homeostatic mechanism in placental development. Understanding condition-specific autophagy dysregulation is thereby crucial for improving pregnancy outcomes. Full article

Background/Objectives: This pilot study aimed to develop and compare advanced machine learning models, specifically a Bayesian-regularized artificial neural network (ANN) and a transformer-enhanced physics-informed neural network (PINN), by integrating periodontal health indices and hematological inflammatory markers for the prediction of GDM. Methods: Utilizing a prospective case–control study design, a clinical dataset comprising 80 pregnant women (40 with GDM and 40 healthy controls) was evaluated to develop and compare advanced machine learning models. Clinical, periodontal, and complete blood count-derived inflammatory parameters were integrated into two predictive models: a Bayesian regularization-based artificial neural network (ANN) and a transformer-enhanced physics-informed neural network (PINN). Model performance was evaluated using the coefficient of determination (R²), mean squared error (MSE), root mean squared error (RMSE), mean absolute error (MAE), and residual error analyses. Results: The ANN demonstrated superior predictive performance, achieving an R² of 0.9872 and an MSE of 3.38 × 10⁻³, compared with an R² of 0.9833 for the PINN model. Residual analysis showed that the ANN provided greater prediction stability, with a mean deviation of 0.5691 and a standard deviation of 3.6400. The findings demonstrate that the integrated analysis of periodontal and hematological markers through advanced neural architectures, particularly the Bayesian-regularized ANN, provides a high-fidelity diagnostic signal for GDM prediction. This integrated feature set, when processed by the proposed machine learning framework, enables the identification of complex biological patterns with remarkable precision. Conclusions: The proposed machine learning framework provides an accurate, non-invasive, and clinically applicable approach for predicting GDM. Integrating routinely available periodontal and hematological data may improve early risk stratification and support personalized prenatal care. Further validation in larger and more diverse populations is warranted before clinical implementation. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse maternal and neonatal outcomes. Xenopsin-Related Peptide-1 (XRP-1) has recently emerged as a potential regulator of glucose metabolism and insulin homeostasis. This study evaluated serum XRP-1 levels and assessed their diagnostic performance in women with GDM. Methods: In this prospective observational study, 120 pregnant women between 24 and 28 weeks of gestation were enrolled, including 60 women with GDM and 60 healthy controls. Serum XRP-1 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical, and obstetric characteristics were compared between groups. Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression were performed to evaluate the diagnostic performance and independent association of XRP-1 with GDM. Results: Serum XRP-1 levels were significantly higher in women with GDM than in healthy controls (3.45 ± 0.47 vs. 2.87 ± 0.46 ng/mL, p = 0.003). ROC analysis demonstrated moderate discriminatory performance for XRP-1 in identifying GDM (AUC = 0.658, 95% CI: 0.560–0.750), with an optimal cut-off value of 3.12 ng/mL, corresponding to 63.3% sensitivity and 61.7% specificity. Multivariable logistic regression demonstrated that serum XRP-1 remained independently associated with GDM after adjustment for maternal age, pre-pregnancy body mass index, gestational weight gain, and parity (adjusted OR 2.74, 95% CI 1.31–5.73; p = 0.007). HbA1c and C-reactive protein levels were also significantly higher in the GDM group. Conclusions: Serum XRP-1 concentrations were independently associated with GDM and demonstrated moderate diagnostic accuracy. Although XRP-1 cannot replace established diagnostic methods, it may represent a complementary biomarker for identifying gestational dysglycemia. Larger multicenter studies are required to validate its clinical utility. Full article

Background: Fetal programming, conceptualized within the Developmental Origins of Health and Disease framework, describes how intrauterine exposures may shape long-term offspring physiology and disease susceptibility. Metformin is increasingly used during pregnancy for gestational diabetes mellitus, type 2 diabetes mellitus, and selected cases of polycystic ovary syndrome. Its developmental interpretation is complex because the drug improves the maternal metabolic environment but also crosses the placenta and directly exposes the fetus. Methods: This focused narrative review used iterative, targeted searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify pharmacological, placental, mechanistic, clinical, guideline-based, and offspring follow-up evidence. The literature search covered publications available through 31 May 2026. The manuscript was subsequently revised during the editorial submission and peer-review process, and the evidence synthesis was re-evaluated against this final literature cut-off date. Earlier landmark studies were retained where necessary for historical, pharmacological, or methodological context. Results: Metformin reduces hepatic glucose production and maternal insulin resistance and may limit gestational weight gain, insulin requirements, neonatal hypoglycemia, and excessive fetal growth in selected pregnancies. Placental transfer creates biological plausibility for direct effects on AMPK, mitochondrial, mTOR, nutrient-sensing, and epigenetic pathways. Long-term studies are broadly reassuring regarding neurodevelopment and major metabolic disease, but findings on growth trajectory, adiposity, and small-for-gestational-age risk remain heterogeneous and indication-dependent. Conclusions: Metformin should be interpreted neither as uniformly beneficial nor as developmentally neutral. Its use should be individualized according to maternal phenotype, indication, glycemic benefit, placental function, fetal growth, dose, timing, and the limitations of long-term offspring evidence. Full article

Background: Hypertensive disorders of pregnancy (HDP), particularly gestational hypertension and preeclampsia, are major causes of maternal and perinatal morbidity. Metabolic disorders such as gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), obesity, and polycystic ovary syndrome (PCOS) share mechanisms with HDP, including insulin resistance, inflammation, oxidative stress, endothelial dysfunction, and placental maladaptation. Metformin may influence these pathways, but its clinical effect on hypertensive outcomes remains uncertain. Methods: A focused narrative review was conducted using structured, targeted searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for literature published primarily from January 2015 through March 2026, supplemented by landmark studies, clinical guidelines, randomized trials, large observational cohorts, systematic reviews, meta-analyses, and mechanistic and placental studies. Evidence was selected for its relevance to the predefined phenotype-based framework and synthesized qualitatively across mechanistic, clinical, and translational domains. Results: Metformin improves insulin sensitivity and may reduce gestational weight gain, metabolic stress, inflammatory signaling, and oxidative stress. Some randomized trials and meta-analyses in GDM, obesity, and PCOS suggest lower rates of pregnancy-induced hypertension or preeclampsia, whereas recent randomized and population-based studies report neutral effects. Findings are limited by heterogeneous populations, late treatment initiation, variable comparators, supplemental insulin use, inconsistent HDP definitions, and insufficient statistical power. Conclusions: Metformin may act as a metabolic and vascular modifier in selected pregnancies, but current evidence does not support its routine use specifically for HDP prevention. Its public health value lies primarily in accessible metabolic treatment and integration into comprehensive antenatal and postpartum risk reduction pathways, rather than replacement of aspirin, blood pressure surveillance, or maternal–fetal monitoring. Full article