Maternal and placental inflammatory activity is carefully regulated during pregnancy and changes in inflammatory status are associated with pregnancy complications and health deficits in the offspring including adverse effects on neurodevelopment. Overweight/obesity is associated with chronic inflammation, thereby contributing to adverse effects. Disturbingly, overweight and obesity are highly prevalent among pregnant women worldwide. Vitamin D (vitD) possess immunomodulatory effects and is believed to support healthy pregnancy. Endocrinological societies recommend empiric vitD supplementation in pregnancy but there is no consensus on the minimal supplementation dose METHODS: An adjacent study to GRAVIT-D (no. NCT04291313, ClinicalTrial.gov), a double-blinded randomized trial investigating the clinical benefits of increasing vitD supplementation in pregnancy from 400IU to 3600IU/day from gestational week 11-16 onwards. In a subgroup, (n = 156), multiplex ELISA targeting third-semester serum levels of IL-1β, IL-6, IL-10, TNFα, MCP-1, and IL-17A was performed. Inflammation signals were correlated with the vitD dose given, subsequently analysing the effect of vitD in relation to the pre-pregnancy body mass index (BMI) within each treatment arm comparing the inflammatory response in WHO-defined BMI groups, < 25, 25-30 and > 30 kg/m2.

High pre-pregnancy BMI was associated with increased IL6 and MCP1 in both the 400IU and the 3600 IU exposed group. IL1β levels increased with BMI if using a 400IU/day supplement. High dose vitD supplementation ameliorated BMI effects on IL1β.

Increased vitD supplementation during pregnancy may ameliorate some overweight/obesity-induced inflammatory activity. Further studies are needed to determine the vitD need in pregnancies complicated by obesity and overweight.

Obesity is a chronic and complex disease defined as the excessive accumulation of body fat and is one of the leading public health problems in developed and developing countries. Due to the importance of obesity, this study was conducted to investigate the prevalence of obesity in the older adults.

meta-analysis.

In this study, systematic review and meta-analysis of study data on the prevalence of obesity in the older adults in the world using keywords including: prevalence, outbreak, Body Mass Index, BMI, obesity, Elderly, aged, older adult, in Science Direct databases, Scopus, PubMed, Web of Science, Iran Doc, Mag Iran, SID and Google Scholar search engine were extracted without time limit until August 2020. The target population under study is the world's elderly, and obesity means a BMI≥30. The Random Effects Model was used to perform the analysis and, Comprehensive Meta-Analysis Software version 2.0 was used for data analysis.

In review 44 studies with a total sample size of 45,745,944 prevalence of obesity in the older adults of the world; In a meta-analysis of 25.3 % (95 % CI: 21.9-29). It was found that the highest prevalence of obesity in the older adults in South America with 40.4 % (95 % CI: 12.5-76.4). In addition, continental Europe with 33.6 % (95 % confidence interval: 24.1-44.5). The meta-regression results showed an increasing trend in the prevalence of obesity in the older adults in the world with an increasing sample size and a decreasing trend with increasing the study (P < 0.05).

Given that the prevalence of obesity in the older adults is high, health policymakers must take adequate measures to increase public awareness about the risks of obesity in the older adults.

Necroptosis, a distinctive form of programmed cell death differs mechanistically from apoptosis pyroptosis, and autophagy, is characterized by the activation of receptor-interacting protein kinases (RIPK1/RIPK3) and their downstream effector, mixed lineage kinase domain-like protein (MLKL). This programmed cell death pathway serves as a crucial mediator of inflammatory responses and has been implicated in the pathogenesis of diverse pathological conditions. Recent evidence has implicated dysregulated necroptosis in the pathogenesis of severe pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), recurrent spontaneous abortion (RSA), and gestational diabetes mellitus (GDM). In these disorders, necroptosis promotes placental dysfunction through multiple interconnected mechanisms: amplification of pro-inflammatory cytokine cascades, aberrant immune activation, disruption of plasma membrane integrity, and subsequent tissue injury.These pregnancy-related pathologies consistently demonstrate elevated necroptotic signatures, correlating with adverse maternal-fetal outcomes. This comprehensive review synthesizes current understanding of the molecular mechanisms underlying necroptosis, with particular emphasis on its pivotal role in the etiopathogenesis of pregnancy-related disorders. Furthermore, we critically evaluate the therapeutic potential of targeting the necroptotic signaling axis, providing novel perspectives for developing targeted interventions to improve clinical outcomes in complicated pregnancies.

Maternal obesity significantly increases the risk of adverse outcomes for the mother and fetus. Fermented wheat germ (FWG) has demonstrated the potential to improve metabolic disorders, yet its effects have not been explored in maternal obesity models. This study investigated the ameliorating impact of FWG in rats with maternal obesity, focusing on its mechanisms through biochemical, gut microbiome, and serum metabolomics analysis. The results demonstrated that FWG was more effective than wheat germ in reducing body weight gain and fat accumulation, improving glycolipid metabolism disorders, and alleviating inflammation. Specifically, FWG modulated the composition of gut microbiota by fostering the growth of beneficial bacteria (e.g., Corynebacterium) while suppressing genera associated with maternal obesity (e.g., Blautia, Akkermansia, Dorea_A, and Faecousia). Furthermore, FWG modified high-fat diet-induced metabolites, primarily affecting pyrimidine metabolism and amino acid metabolism. These findings suggest that FWG may serve as a promising dietary intervention for mitigating maternal obesity and improving pregnancy outcomes.

Inflammasomes are multiprotein complexes that initiate inflammatory responses by activating pro-inflammatory cytokines, playing a crucial role in innate immunity. However, their dysregulation can lead to excessive inflammation, particularly in conditions like gestational diabetes mellitus (GDM), where placental inflammation may adversely affect fetal development and increase the risk of complications. NEK7 (NIMA-related kinase 7) has been identified as a key mediator in inflammasome activation, facilitating the complex assembly and amplifying inflammatory responses. This study aims to investigate the regulatory role of miRNA in inflammasome-mediated placental inflammation through its interaction with NEK7 in the pathophysiology of GDM. In-silico analysis identified that NEK7 is a direct target of miR-186-5p, while PCR analysis demonstrated a significant loss of miR-186-5p expression in GDM placental tissues. Further, the expressions of NEK7, NLRP1, NLRP3, Caspase 1 along with the inflammatory cytokines were significantly elevated in GDM placenta. Furthermore, the correlation analysis demonstrated a significant negative correlation between miR-186-5p and NEK7 expression levels, suggesting that the loss of miR-186-5p may contribute to inflammasome mediated placental inflammation in GDM. Additionally, the overexpression of miR-186-5p decreased the high glucose induced inflammation and the expressions of NEK7, NLRP1 and NLRP3 in BeWo cell line. Therefore, this study concludes that miR-186-5p may attenuate the activation of inflammasome and regulate inflammation via NEK7 in the progression of GDM. Understanding these molecular mechanisms offers valuable insights into potential therapeutic targets aimed at improving pregnancy outcomes in GDM.

During pregnancy, the maternal body adapts in several ways to create an optimal environment for embryonic growth. These changes include endocrine and metabolic shifts that can lead to insulin resistance and gestational diabetes mellitus (GDM), impacting both the mother and fetus in the short and long term. Fetal macrosomia, a condition where the fetus is significantly larger than average, is a primary concern associated with GDM. Although the underlying mechanism remains unclear, a pregnancy-induced proinflammatory state, combined with altered glucose homeostasis, plays a critical role. Several cytokines and hormones, such as interleukin 6 (IL-6), insulin growth factor 1 (IGF-1), prolactin (PRL), or progesterone, are essential for fetal growth, the control of the inflammatory response, and the regulation of lipid and carbohydrate metabolism to meet energy demands during pregnancy. However, although the role of these cytokines in metabolism and body growth during adulthood has been extensively studied, their implication in the pathophysiology of GDM and macrosomia is not well understood. Here, we review this pathophysiology and pose the hypothesis that an aberrant response to cytokine receptor activation, particularly involving the suppressor of cytokine signaling 2 (SOCS2), contributes to GDM and fetal macrosomia. This novel perspective suggests an unexplored mechanism by which SOCS2 dysregulation could impact pregnancy outcomes.

Introduction: docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an important role in fetal growth and development. In Mexico, 76.8 % of women of reproductive age are overweight and obese, which is associated with the development of gestational complications. EPA and DHA fatty acids have an anti-inflammatory effect, reducing the risk of developing complications. Objective: to evaluate the erythrocyte and dietary profile of omega-3 fatty acids in overweight and obese pregnant women. Materials and methods: a prospective, cross-sectional, comparative and observational study in pregnant women with less than 14 weeks of gestation. Dietary intake of omega-3 fatty acids was evaluated by dietary diary; and levels of omega-3 fatty acids in erythrocyte membranes were evaluated by gas chromatography. Results: the mean dietary intake of EPA and DHA fatty acids was 0.027 g and 0.095 g, respectively. The erythrocyte profile was 2.90 for EPA and 1.50 DHA, no differences between normal and overweight women was found. Conclusion: the dietary intake and erythrocyte profile of omega-3 of pregnant women is lower than the reference parameters, with no significant differences between normal and overweight women.

While substantial literature exists on the intersection of overweight/obesity (OWO) and pregnancy, much of it focuses on specific aspects, making it difficult to maintain an overview of clinically relevant factors for optimal care of OWO women throughout pregnancy.

To provide a comprehensive synthesis of the existing literature, covering the full spectrum of clinically relevant information needed to manage OWO women from preconception to birth.

For this narrative review a literature search was conducted on PubMed in January 2025. Eligible studies included full-text English articles with data from human subjects, with no restrictions on publication date.

The impact of OWO on pregnancy is multifaceted, encompassing four interrelated themes: physiological consequences, emerging risks, challenges in prenatal care, and intervention strategies. OWO women exhibit differences in metabolic and inflammatory pathways compared to normal-weight women, reflected in altered laboratory tests. When managing gestational diabetes and preeclampsia, obesity-related characteristics must be considered. Clinicians need to be alert of obesity-mediated fetal complications, including overgrowth, malformations, stillbirth, and preterm birth, while navigating challenges in ultrasound measurements. Interventions during the preconception and prenatal periods provide key opportunities to optimize maternal weight and reduce the risk of long-term disease development.

The review's insights enhance clinical practice and call on researchers and policymakers to prioritize strategies that offer early counseling for obese pregnant women. These initiatives aim to optimize outcomes for both mother and child and contribute to combating the global obesity crisis.

This study investigated whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in early pregnancy correlate with subsequent development of gestational diabetes mellitus (GDM).

This prospective cohort study enrolled 1,200 pregnant women during their first trimester at Peking University International Hospital between December 2017 and March 2019. All participants underwent oral glucose tolerance testing (OGTT) at 24-28 weeks gestation. Complete blood counts obtained in the first trimester were analyzed for NLR and PLR values. Participants were categorized into GDM (n=227) and non-GDM (n=973) groups based on International Association of Diabetes and Pregnancy Study Groups criteria.

Women who developed GDM exhibited significantly higher first-trimester levels of neutrophils, lymphocytes, platelets, NLR, and PLR (all p<0.05) compared to women without GDM. First-trimester NLR and PLR values positively correlated with second-trimester blood glucose levels at 0, 60, and 120 minutes during OGTT (all p<0.05). The optimal cut-off values for predicting GDM were 3.89 for NLR (sensitivity 76.05%, specificity 36.56%) and 148.11 for PLR (sensitivity 68.72%, specificity 68.65%). A multivariate predictive model incorporating NLR, PLR, age, parity, BMI, blood lipids, and uric acid demonstrated 78.39% sensitivity, 73.83% specificity, and 78.87% accuracy with an area under the curve of 0.79 (95% CI: 0.71, 0.86).

First-trimester NLR and PLR represent independent risk factors for GDM development. These readily available inflammatory markers may have value for early GDM risk assessment and aid in targeting preventive interventions.

Emerging research suggests that the intrauterine environment plays a critical role in predisposing individuals to metabolic syndrome (MetS), a constellation of conditions that heightens the risk for heart disease, stroke, and diabetes. Traditionally linked to lifestyle, the risk for MetS is now understood to be also influenced by fetal exposures. The environment in which a child lives offers abundant potential sources that can contribute to an increased risk of developing various diseases, and in some cases, these factors can be avoided. This review integrates findings from both epidemiological and experimental research to underscore the impact of prenatal factors, including maternal nutrition, obesity, gestational diabetes (GDM), and birth size, on the subsequent development of metabolic derangements in offspring, particularly during puberty. The progression of genetic and epigenetic studies has enlightened the pathophysiology of these conditions starting in the intrauterine period and continuing into early life. By examining data and studies, this article elucidates the prenatal influences and underlying mechanisms that contribute to the pathogenesis of MetS. The updated understanding of the link between the intrauterine environment and future health comorbidities will draw attention to intrauterine care and maternal health and contribute to the prevention of serious diseases in adulthood.

Congenital heart defects (CHD) are the most common major birth defects and one of the leading causes of death from congenital defects after birth. CHD can arise in pregnancy from the combination of genetic and non-genetic factors. The maternal immune activation (MIA) hypothesis is widely implicated in embryonic neurodevelopmental abnormalities. MIA has been found to be associated with the development of asthma, diabetes mellitus, and other diseases in the offspring. Given the important role of cardiac immune cells and cytokines in embryonic heart development, it is hypothesized that MIA may play a significant role in embryonic heart development. This review aims to stimulate further investigation into the relationship between MIA and CHD and to highlight the gaps in the knowledge. It evaluates the impact of MIA on CHD in the context of pregnancy complications, immune-related diseases, infections, and environmental and lifestyle factors. The review outlines the mechanisms by which immune cells and their secretome indirectly regulate the immuno-microenvironment of the embryonic heart by influencing placental development. Furthermore, the inflammatory cytokines cross the placenta to induce related reactions including oxidative stress in the embryonic heart directly. This review delineates the role of MIA in CHD and underscores the impact of maternal factors, especially immune factors, as well as the embryonic cardiac immuno-microenvironment, on embryonic heart development. This review extends our understanding of the importance of MIA in the pathogenesis of CHD and provides important insights into prenatal prevention and treatment strategies for this congenital condition.

Pregnancy alters the systemic exposure and clearance of many hepatically cleared drugs that are commonly used by obstetric patients. Understanding the molecular mechanisms underlying the changes in factors that affect hepatic drug clearance (blood flow, protein binding, and intrinsic clearance) is essential to more precisely predict systemic drug exposure and dose requirements in obstetric patients.

This review (1) summarizes the anatomic, physiologic, and biochemical changes in maternal hepatic, cardiovascular, endocrine, and renal systems relevant to hepatic drug clearance and (2) reviews the molecular mechanisms underlying the altered hepatic metabolism and intrinsic clearance of drugs during pregnancy via a comprehensive PubMed search. It also identifies knowledge gaps in the molecular mechanisms and factors that modulate hepatic drug clearance during pregnancy.

Pharmacokinetic studies have shown that pregnancy alters systemic exposure, protein binding, and clearance of many drugs during gestation in part due to pregnancy-associated decreases in plasma albumin, increases in organ blood flow, and changes in the activity of drug-metabolizing enzymes (DMEs) and transporters. The changes in the activity of certain DMEs and transporters during pregnancy are likely driven by hormonal-changes that inhibit their activity or alter the expression of these proteins through activation of transcription factors.

  We aimed to examine both the expression levels of high mobility group box 1 (HMGB1) and vascular cell adhesion molecule-1 (VCAM-1) proteins in the placentas of pregnant women with gestational diabetes mellitus (GDM) and control groups by immunohistochemical (IHC) method.

  An experimental case-control study was conducted, including 40 pregnant women complicated with GDM and 40 healthy pregnant women. Placental tissues obtained following cesarean delivery were subjected to routine tissue monitoring. The placental sections were stained with VCAM-1 and HMGB1 immunostains and subjected to IHC examination under a light microscope. H-score (HS) was used to evaluate the results of IHC staining by semi-quantitative analysis. Pathway analysis in Cytoscape software identified GDM-associated proteins within HMGB1 and VCAM-1 interaction networks, followed by GO analysis to explore associated biological processes.

  Placental HGMB1 expression was significantly increased in the GDM group compared to the control group (p<0.001). However, placental VCAM-1 expression was found to be statistically similar in GDM and control groups (p=0.584). The shared 19 proteins were identified between HMGB1 and GDM, and 13 between VCAM-1 and GDM, with notable GO biological process terms such as immune system activation for HMGB1 and interleukin-6 regulation for VCAM-1 associated with GDM.

  We consider that GDM-related inflammation and oxidative stress may contribute to tissue damage and inflammation by increasing placental HMGB1 expression. The blockade of HMGB1 and its receptors might represent a promising therapeutic approach to control inflammation in GDM. Understanding the distinct roles of HMGB1 and VCAM-1 may provide valuable insights for the development of targeted therapies aimed at mitigating the inflammatory processes associated with GDM and improving maternal and fetal outcomes.

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and significantly increases both maternal and fetal morbidity and mortality. Inflammation is a hallmark of GDM, and placental inflammation may play a key role in the pathophysiology of the disease. Myeloid-derived suppressor cells (MDSCs), which are innate immunosuppressive, are thought to contribute to feto-maternal tolerance. In normal pregnancies, elevated levels of MDSCs have been observed in both peripheral and umbilical cord blood. Our hypothesis postulates that trophoblasts from placentas belonging to women with GDM may have lower levels of MDSCs compared to trophoblasts from placentas originating from healthy pregnancies. Furthermore, since leptin is overexpressed in the placenta of GDM patients, we hypothesized that leptin might contribute to the reduction of MDSCs. To test this, we investigated the in vitro effects of leptin on MDSC levels in isolated peripheral blood leukocytes after 24 h of incubation. Our findings indicate that trophoblasts from placentas from women with GDM contain a lower percentage of MDSCs compared to trophoblasts from healthy pregnancies. In addition, in vitro studies demonstrated that leptin reduces the number of MDSCs in peripheral blood leukocytes. In conclusion, MDSCs are decreased in placentas from pregnancies with GDM, and leptin appears to reduce the number of MDSCs in leukocytes isolated in vitro. Increased leptin expression in trophoblasts from placentas of women with GDM may contribute to the lower levels of MDSCs, potentially playing a role in placental inflammation. However, further investigations are required to fully elucidate this mechanism.

Maternal obesity impairs placental function, affecting fetal growth and long-term health. Although fermented wheat germ (FWG) provides health benefits, its impact on maternal obesity-related metabolic disorders and placental function remains unclear. This study investigated FWG's effects on placental morphology, metabolism, and nutrient transport in high-fat diet (HFD)-induced obese maternal rats. Wheat germ (WG) and FWG were administered from model induction, with a 45% HFD-fed for 10 weeks before conception and continued until gestational day 19.5. Results revealed that WG and FWG supplementation alleviated maternal metabolic abnormalities and mitigated placental structural damage. Additionally, this supplementation reduced placental lipid accumulation, oxidative stress, and inflammation while regulating nutrient transporter mRNA expression and inhibiting mTOR signaling activation. Compared with WG, FWG more effectively reduced maternal obesity and optimized placental nutrient transport. These findings suggest that FWG is a promising dietary intervention for disrupting the maternal obesity cycle and enhancing maternal-fetal health by alleviating obesity, mitigating metabolic dysfunction, and modulating placental morphology and function.

Gestational diabetes mellitus (GDM) affects placental metabolism, influencing both maternal and fetal outcomes. This study investigated the expression of metabolic regulators-Pyruvate Kinase M2 (PKM2), AMP-activated protein kinase (AMPK), and mTOR pathway components-in placental tissues from GDM pregnancies managed with either insulin (GDM-I) or dietary interventions (GDM-D). We hypothesize that metabolic adaptation in GDM is differentially regulated by treatment modality. This study analyzed 30 cases, including 10 control pregnancies,10 GDM-D cases, and 10 GDM-I cases. Analytical methods included immunofluorescence and immunoblotting. We observed an upregulation of PKM2 in both GDM-I and GDM-D placentas, suggesting enhanced glycolytic adaptation under GDM-induced metabolic stress. AMPK expression was significantly elevated in GDM-I and moderately increased in GDM-D placentas, potentially compensating for insulin resistance by promoting glucose uptake and energy homeostasis. Furthermore, mTOR pathway activation differed by treatment type, suggesting a treatment-specific mTOR response. The metabolic changes observed suggest that treatment modality in GDM may have direct implications for maternal and fetal health. Our findings indicate that while insulin and dietary management support metabolic adaptation in GDM, they do so through distinct mechanisms. These findings support a personalized approach in GDM treatment, where patient-specific metabolic responses should guide therapeutic decisions.

Introduction: Gestational diabetes mellitus (GDM) is a major health concern during pregnancy, affecting both the mother and the baby. Immune system alterations, particularly changes in lymphocyte subsets and cytokine profiles, have been associated with the pathophysiology of various metabolic disorders, including diabetes. This study is aimed at systematically reviewing the literature on the changes in lymphocyte subsets and cytokines in GDM. Methods: In this systematic review, we applied specific criteria to select observational studies (such as case-controls, cross-sectionals, or cohorts) that focused on pregnant women. We performed an extensive search across electronic databases, including Web of Science, Scopus, PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar, from January 1, 2010, to March 20, 2024. Results: A total of 19 articles, with 2517 participants (1128 with GDM and 1389 without GDM), were included in the qualitative synthesis. Due to high heterogeneity among the articles, a meta-analysis was not conducted. The studies assessed 35 different lymphocyte subsets or proportions. The most commonly assessed subsets were CD3+ T cell (five articles, mostly no difference between GDM and non-GDM), CD4+ T cell (five articles with contradictory results), CD8+ T cell (four articles with contradictory results), B cell and NK cell (three articles, mostly no difference between GDM and non-GDM), and Tregs (three articles with contradictory results). Additionally, 32 cytokines or proportions were assessed in the studies. The most commonly assessed cytokines were IL-6 (eight articles, higher or similar levels in GDM compared to non-GDM), TNF-α (seven articles, mostly higher or similar levels in GDM compared to non-GDM), IL-10 (six articles, mostly no difference between GDM and non-GDM), IL-2 (three articles, mostly no difference between GDM and non-GDM), and IFN-γ (three articles with contradictory results). Conclusion: According to the results, there were no significant changes in CD3+ T cells, B cells, NK cells, IL-10, and IL-2 in GDM. However, the levels of IL-6 and TNF-α were higher or similar in GDM compared to non-GDM. The changes of other lymphocyte subsets and cytokines in GDM remained unclear.

Mitochondria play a central role in nutrient metabolism, besides being responsible for the production of adenosine triphosphate (ATP), the main source of cellular energy. However, the ATP production process is associated with the generation of reactive oxygen species (ROS), which excessive accumulation can cause mitochondrial dysfunction. This dysfunction, in turn, causes the accumulation of fatty acids in the adipose tissue, triggering a local inflammatory process that can evolve into systemic inflammation. In women with obesity, an increase in lipid levels in the placental environment is observed. The high presence of fatty acids compromises the structural integrity and mitochondrial membrane, culminating in the release of ROS. This process damages the DNA of placental cells and causes an inflammatory state, affecting metabolic efficiency. This vicious cycle is characterized by defects in mitochondrial ATP production, which can lead to lipid accumulation and inflammation. In pregnant women with obesity, these mitochondrial changes play a determining role in pregnancy outcomes. Hence, the objective of this study was to search the literature to review the impact of mitochondrial dysfunction in the maternal obesity.

Goals: The aim of this paper was to do a demographic analysis of the population of pregnant women in Serbia and to summarize data regarding: their health related habits during pandemic years, pregnancy course, and the impact the COVID-19 pandemic on their mental health. Methods: The study was prospective observational non-randomized study in the public health. A group of 1,019 patients were included in this prospective cross-sectional observational study. The patients were assessed using a questionnaire designed by the International Federation of Gynecology and Obstetrics which was implemented cross-country in primary healthcare institutions during regular pregnancy visits. Data was collected during the first pandemic year in 2020. The IMB SPPS 27 program was used for descriptive statistical analysis of the collected data. Results: Out of the respondents 10.6% had elevated blood pressure. The mean fasting level of glucose was within the suggested limit. Almost all pregnant women were not on any special diet, and the most common special nutritional regime was a diabetic diet. Most respondents were non-smokers and most of them practiced some kind of recreation. Almost all pregnant women adhered to protective measures during the pandemic and more than half of them felt increased stress due to the situation. Conclusion: Our research suggests that despite the increased psychological pressure and restrictive measures which took place during the first pandemic year the Serbian population of pregnant women managed to follow majority of the health recommendations, including the protective measures from the COVID-19 virus.

MicroRNAs, a class of small non-coding RNA molecules that regulate gene expression post-transcriptionally, are implicated in various pathological conditions including diabetes mellitus (DM). DM has been increasingly recognized as an inflammatory disease and monocytes play a key role in propagating inflammation under hyperglycemic conditions. We hypothesize that high glucose dysregulates microRNAs to promote monocyte inflammatory activity, which may contribute to the pathogenesis of DM. THP-1 monocytes were cultured in normal (5 mM) and high (25 mM) glucose conditions. RT-qPCR and Western blotting were performed to assay microRNAs and proteins, respectively. Monocytes were transfected with microRNA mimics using Lipofectamine RNAiMAX reagent. THP-1 monocyte growth was assessed using Calcein-AM dye and a Boyden chamber assay was applied to measure monocyte migration. The results showed that high glucose downregulated miR-139-5p associated with increased protein expression of CXCR4, an experimentally validated target of miR-139-5p. Correspondingly, treatment with high glucose resulted in a significant increase in THP-1 cell migration towards SDF-1, a cognate ligand for CXCR4. MiR-139-5p overexpression inhibited high glucose-induced CXCR4 expression, leading to reduced cell migration towards SDF-1. High glucose did not affect THP-1 monocyte growth. In conclusion, the miR-139-5p-CXCR4 axis may play a role in high glucose-induced inflammation by regulating monocyte migration.

Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) are public health concerns worldwide. These two diseases share the same pathophysiological and genetic similarities. This study aimed to investigate the T2DM known single nucleotide polymorphisms (SNPs) of the adiponectin C1Q and collagen domain containing (ADIPOQ), cyclin-dependent kinase inhibitor 2A and 2B (CDKN2A/2B), and signal sequence receptor subunit 1 (SSR1) genes in a cohort of Romanian GDM pregnant women and perinatal outcomes. DNA was isolated from the peripheral blood of 213 pregnant women with (n = 71) or without (n = 142) GDM. Afterward, ADIPOQ (rs266729), CDKN2A/2B (rs10811661), and SSR1 (rs9505118) gene polymorphisms were genotyped using TaqMan Real-Time PCR analysis. Women with GDM had a higher pre-pregnancy body mass index (BMI) (p < 0.0001), higher BMI (p < 0.0001), higher insulin resistance homeostatic model assessment (IR-HOMA) (p = 0.0002), higher insulin levels (p = 0.003), and lower adiponectin levels (p = 0.004) at birth compared to pregnant women with normoglycemia. GDM pregnant women had gestational hypertension (GH) more frequently during pregnancy (p < 0.0001), perineal lacerations more frequently during vaginal birth (p = 0.03), and more macrosomic newborns (p < 0.0001) than pregnant women from the control group. We did not find an association under any model (allelic, genotypic, dominant, or recessive) of ADIPOQ rs266729, CDKN2A/2B rs10811661, and SSR1 rs9505118 polymorphisms and GDM. In correlation analysis, we found a weak positive correlation (r = 0.24) between the dominant model GG + CG vs. CC of rs266729 and labor induction failure. In the dominant model TT vs. CC + CT of rs10811661, we found a weak negative correlation between this model and perineal lacerations. Our results suggest that the ADIPOQ rs266729, the CDKN2A/2B rs10811661, and the SSR1 rs9505118 gene polymorphisms are not associated with GDM in a cohort of Romanian pregnant women.

 This study aimed to evaluate the frequency of adverse maternal and neonatal outcomes associated with maternal obesity in a Hispanic population. We hypothesized that obesity confers a dose-dependent risk associated with these outcomes.

 This was a retrospective cohort study of singleton pregnancies delivered between 24 and 42 weeks gestation at an urban county hospital between 2013 and 2021. Body mass index (BMI) at the first prenatal visit was used as a proxy for prepregnancy weight. Patients were excluded if their first-trimester BMI was not available. Trends in adverse outcomes across increasing obesity classes were assessed.

 During the study period, 58,497 patients delivered a singleton infant, of which 12,365 (21.1%), 5,429 (9.3%), and 3,482 (6.0%) were in class I, II, and III obesity, respectively. Compared with nonobese patients, obese patients were more likely to be younger and nulliparous with a higher incidence of hypertension and pregestational diabetes. Higher BMI was associated with a significant dose-dependent increase in cesarean delivery (27% for nonobese, 34% for class I, 39% for class II, and 46% for class III obesity); severe preeclampsia (8% in nonobese and 19% for class III obesity); and gestational diabetes (5% in nonobese and 15% in class III obesity). There were significant trends in increasing morbidity for infants born to patients with correspondingly higher obesity classes. Some of these adverse outcomes included respiratory distress syndrome, neonatal intensive care unit admission, fetal anomalies, and sepsis (all p < 0.001).

 Increasing body mass index is associated with a significant dose-dependent increase in multiple adverse perinatal outcomes in a Hispanic population. Associated adverse maternal outcomes include severe preeclampsia, gestational diabetes, and cesarean delivery. Infants born to patients with correspondingly higher BMI class have significantly increased associated morbidity. Often, only higher BMI classes are significantly associated with these adverse outcomes.

· As BMI increases, pregnant patients are more likely to experience adverse maternal and neonatal outcomes.. · Many adverse pregnancy outcomes are associated only with a BMI greater than 40 kg/m2.. · Obesity is associated with cesarean delivery, likely due to an increase in labor dystocia..

To examine the association between dietary inflammatory index (DII) and risk of gestational diabetes mellitus (GDM).

A prospective birth cohort study was conducted in Iran. During the first trimester of pregnancy, food intake was measured using a food frequency questionnaire. Each participant's DII score was calculated, and then, the Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% CI of GDM across the quartiles of DII. We systematically searched the literature to conduct a meta-analysis of observational studies (PROSPERO: CRD42022331703). To estimate the summary relative risk for the highest versus lowest category of DII, a random-effects meta-analysis was performed. The certainty of evidence was assessed using the GRADE approach.

In the prospective cohort study (n = 635 pregnant mothers), the multivariable HRs of GDM for the third and fourth quartiles of DII were 2.98 (95%CI: 1.98, 6.46) and 2.72 (95%CI: 1.11, 6.63), respectively. Based on a meta-analysis of six prospective cohorts and a case-control study (1014 cases of GDM in 7027 pregnant mothers), being in the highest category of the DII was associated with a 27% higher risk of GDM (relative risk: 1.27, 95%CI: 1.01, 1.59; I2 = 50%; low certainty of evidence). A dose-response meta-analysis suggested a positive monotonic association between DII and GDM risk.

Our prospective cohort demonstrated a positive correlation between GDM risk and the inflammatory potential of diet in the first trimester of pregnancy. The results need to be confirmed by larger cohort studies.

Not applicable.

Gestational diabetes mellitus (GDM) continues to pose a significant challenge to maternal and fetal health, driving the need for advanced diagnostic and therapeutic strategies. Biomarker discovery has proven essential for early detection, mechanistic insights, and targeted interventions. This review provides an in-depth examination of biomarkers related to GDM, focusing on glucose metabolism, insulin resistance, inflammatory signaling, adipokines, oxidative stress markers, and genetic/epigenetic determinants. We also evaluate novel biomarkers emerging from omics technologies and their translational potential in clinical practice. Additionally, we explore the role of microRNAs and extracellular vesicles as emerging biomarkers that could offer new perspectives on GDM pathophysiology. Integration of these biomarkers into predictive models holds the potential to improve risk assessment and patient health outcomes.

To investigate the association between gestational diabetes mellitus (GDM) and blood levels of gelsolin (an inflammation-related protein thought to be reduced in type 2 diabetes mellitus) and to determine its role in potential diagnosis and neonatal outcomes.

This prospective case-control study was conducted at Ankara Etlik City Hospital between November 2023 and February 2024 with 40 pregnant women with GDM and 40 normoglycemic women. Pregnant women aged 18-40 years who were in their 24th to 28th week of pregnancy and had no known chronic disease were included in the present study and it was investigated as to whether there was a significant difference between the two groups in terms of gelsolin levels and neonatal outcome.

Gelsolin level was statistically significantly lower in the GDM group than in the control group (P = 0.004). In patients with fasting blood glucose <96 mg/dL, maternal serum gelsolin levels were associated with GDM, with a cut-off of 15.38 or less, showing a sensitivity of 73%, a specificity of 67%, and an area under the curve (AUC) of 0.703 (95% confidence interval [CI] 0.576-0.810, P = 0.002). There was no difference between groups in terms of adverse obstetric outcomes, but gelsolin levels were associated with composite neonatal adverse outcome (macrosomia, Apgar score at 5 min less than 7, preterm birth, need for neonatal intensive care), with a cut-off value of 16.66 or less showing a sensitivity of 84.6%, specificity of 40.7% and AUC of 0.644 (95% CI 0.529-0.748, P = 0.031).

Gelsolin could potentially serve as a promising biomarker for the diagnosis of GDM.

Food cravings, an intense desire to consume specific foods, are a complex interplay of cognitive, emotional, behavioral, physiological, and cultural factors. Although prevalent across genders, food cravings are more frequent and intense in women, with hormonal fluctuations-particularly during the menstrual cycle and pregnancy-playing a significant role. Pregnancy, marked by profound hormonal and physiological shifts, often heightens cravings, likely as a response to the increased metabolic needs of both mother and fetus. However, the tendency to crave high-calorie, palatable foods during this time can lead to excessive weight gain, presenting potential risks to both maternal and fetal health. This chapter examines the neural mechanisms underlying altered eating behaviors during pregnancy and their role in triggering food cravings. We discuss the health implications of disrupted eating patterns in pregnancy, emphasizing the need for further research to advance understanding of female-specific neurobiology and to develop targeted interventions that support healthy eating behaviors, ultimately improving maternal and offspring health outcomes.

Growing evidence shows that dysregulated metabolic intrauterine environments can affect offspring's neurodevelopment and behaviour. However, the results of individual cohort studies have been inconsistent. We aimed to investigate the association between maternal diabetes before pregnancy and gestational diabetes mellitus (GDM) with neurodevelopmental, cognitive and behavioural outcomes in children.

Harmonised data from > 200 000 mother-child pairs across ten birth cohorts in Europe and Australia were available. Mother-child pairs were included for analysis to determine whether GDM was recorded (yes or no) and whether at least one neurodevelopmental, cognitive and behavioural outcome was available in children aged 3 to 13 years. Confounder-adjusted regression models were used to estimate associations between maternal diabetes and child outcomes using two-stage individual participant data (IPD) meta-analysis. Model 1 included a crude estimate. The full adjustment model (model 2) included adjustment for child sex, maternal age, pre-pregnancy BMI, pregnancy weight gain, maternal smoking during pregnancy, plurality, parity and maternal education.

Children (aged 7-10 years) born to mothers with GDM had higher attention-deficient hyperactive disorder (ADHD) symptoms compared to non-exposed controls (model 2, regression coefficient (β) 3.67 (95% CI 1.13, 6.20), P = 0.001). Moreover, children (aged 4-6 years) born to mothers with GDM exhibited more externalising problems than those born to mothers without GDM (model 2, β 2.77 (95% CI 0.52, 5.02), P = 0.01). A pre-existing maternal history of type 1 and type 2 diabetes mellitus was associated with ADHD symptoms at 4-6 years (model 1, β 8.82 (95% CI 2.21, 15.45, P = 0.009) and β 7.90 (95% CI 0.82, 14.98, P = 0.02), respectively). The association was no longer apparent in further adjustments.

This study found that children between 4 - 6 and 7-10 years of age born to mothers with GDM have a greater likelihood of developing externalising problems and ADHD symptoms, respectively. Externalising problems often co-exist with ADHD symptoms and precede formal ADHD diagnosis. Overall, this large-scale multi-cohort study suggested that a dysregulated metabolic environment during pregnancy may contribute to ADHD symptoms and externalising problems in young children.

The immune compartment within fetal chorionic villi is comprised of fetal Hofbauer cells (HBC) and invading placenta-associated maternal monocytes and macrophages (PAMM). Recent studies have characterized the transcriptional profile of the first trimester (T1) placenta; however, the phenotypic and functional diversity of chorionic villous immune cells at term (T3) remain poorly understood.

To address this knowledge gap, immune cells from human chorionic villous tissues obtained from full-term, uncomplicated pregnancies were deeply phenotyped using a combination of flow cytometry, single-cell RNA sequencing (scRNA-seq, CITE-seq) and chromatin accessibility profiling (snATAC-seq).

Our results indicate that, relative to the first trimester, the frequency of fetal macrophages (HBC, proliferating HBC) is significantly reduced, whereas that of infiltrating maternal monocytes/macrophages (PAMM1b, PAMM1a, PAMM2, MAC_1) increased in T3. PAMM1b and HBCs exhibit the most phagocytic capacity at term highlighting their regulatory role in tissue homeostasis in late pregnancy. The transcriptional profiles of resident villous immune subsets exhibit a heightened activation state relative to the relative to T1, likely to support labor and parturition. Additionally, we provide one of the first insights into the chromatin accessibility profile of villous myeloid cells at term. We next stratified our findings by pre-pregnancy BMI since maternal pregravid obesity is associated with several adverse pregnancy outcomes. Pregravid obesity increased inflammatory gene expression, particularly among HBC and PAMM1a subsets, but dampened the expression of antimicrobial genes, supporting a tolerant-like phenotype of chorionic villous myeloid cells. We report a decline in HBC abundance accompanied by an increase in infiltrating maternal macrophages, which aligns with reports of heightened chorionic villous inflammatory pathologies with pregravid obesity. Finally, given the shared fetal yolk-sac origin of HBCs and microglia, we leveraged an in vitro model of umbilical cord blood-derived microglia to investigate the impact of pregravid obesity on fetal neurodevelopment. Our findings reveal increased expression of activation markers albeit dampened phagocytic capacity in microglia with pregravid obesity.

Overall, our study highlights immune adaptations in the fetal chorionic villous with gestational age and pregravid obesity, as well as insight towards microglia dysfunction possibly underlying poor neurodevelopmental outcomes in offspring of women with pregravid obesity.

Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the rs267738 allele of the CERS2 gene in Hispanic women shortly after a GDM pregnancy. To understand the impact of the CERS2 gene and risk allele on glucose regulation, we examined whole-body Cers2 knockout and rs267738 knock-in mice. Both models exhibited glucose intolerance and impaired insulin secretion in vivo. Islets isolated from these models also demonstrated reduced β cell function, as shown by decreased insulin secretion ex vivo. Overall, reduced circulating sphingolipids may indicate a high risk of GDM-to-T2D progression and reflect deficits in CERS2 activity that negatively affect glucose homeostasis and β cell function.

Maternal obstetric characteristics have a key role in determining the occurrence of pregnancy-related disorders and subsequent neonatal outcomes. We aimed to investigate the mediating impact of gestational diabetes mellitus (GDM) and hypertensive disorder of pregnancy (HDP) on the relationship between maternal advanced age, previous caesarean section, and the risk of either large for gestational age (LGA) or small for gestational age (SGA) infants.

We used data from a prospective multicentre cohort study conducted through China's National Maternal Near-miss Surveillance System from January 2012 to December 2021. We performed univariate and multivariate logistic regression analyses to examine the connections between maternal advanced age, previous caesarean section, GDM and HDP, and the risks of LGA and SGA, as well as mediation analyses to assess the mediating effect of GDM and/or HDP on the relationship between maternal advanced age, previous caesarean section, and the risks of LGA and SGA.

We included 482 458 women in our study, of whom13.5% were classified as advanced age, 51.4% as multipara, and 16.3% had a history of uterine scarring. Following adjustments for covariates, we found statistically significant associations between maternal advanced age and GDM (adjusted odds ratio (aOR) = 1.79; 95% confidence interval (CI) = 1.75, 1.83), maternal advanced age and HDP (aOR = 1.93; 95% CI = 1.86, 2.01), previous caesarean section and GDM (aOR = 1.13, 95% CI = 1.11, 1.16), previous caesarean section and HDP (aOR = 1.24; 95% CI = 1.20, 1.28), GDM and LGA (aOR = 1.32; 95% CI = 1.30, 1.35), and HDP and SGA (aOR = 3.93; 95% CI = 3.75, 4.12). The influence of maternal advanced age on SGA was significantly mediated by HDP, accounting for 68.96% of the mediation effect. Furthermore, GDM and HDP served as significant mediators in the relationship between previous caesarean section and the risks of LGA and SGA, with mediation proportions of 5.62% and 4.49%, respectively.

We found HDP has a mediating role in the impact of maternal advanced age and previous caesarean section individually on SGA risk, while GDM acts as a mediator in the connection between previous caesarean section and LGA risk.

The specific influence of the pre-pregnancy body mass index (PPBMI) on women with gestational diabetes mellitus (GDM) is unclear. Our objective was to investigate how PPBMI categories affect pregnancy and neonatal outcomes in women with GDM.

A retrospective cohort study was conducted using data from patients attending the Fujian Maternity and Child Health Hospital (Fuzhou, China) from 2021 to 2023. The participant records were stratified into four groups according to their BMI values: underweight, normal-weight, overweight, and obese. The pregnancy and neonatal outcomes for these BMI categories were analyzed using multivariable logistic regression.

The study included data from 2,909 pregnant women diagnosed with GDM. Underweight women with GDM showed significantly lower risks of pregnancy-induced hypertension (PIH) (adjusted OR, 0.26) and cesarean sections (adjusted OR, 0.55) but higher risks of low body weight (LBW) infants (adjusted OR, 3.40). Overweight and obese women experienced higher risks of PIH (adjusted OR, 2.96), cesarean sections (adjusted OR, 1.62), and macrosomia (adjusted OR, 1.43).

PPBMIs significantly impact pregnancy outcomes in women with GDM. Both underweight and overweight/obese categories are associated with adverse outcomes, highlighting the need for pre-pregnancy counseling and interventions to achieve and maintain a healthy BMI.

Maternal obesity detrimentally affects placental function and fetal development. Both alternate-day fasting (ADF) and time-restricted feeding (TRF) are dietary interventions that can improve metabolic health, yet their comparative effects on placental function and fetal development remain unexplored.

This study aims to investigate the effects of ADF and TRF on placental function and fetal development during maternal consumption of a high-fat diet (HFD).

One hundred 8-week-old female mice were assigned to one of four dietary regimens: (1) normal diet with ad libitum feeding (NA); (2) HFD with ad libitum feeding (HA); (3) HFD with ADF (HI); and (4) HFD with TRF (HT), administered both before and during pregnancy. On gestational day 18.5, serum and placental samples were collected from both mothers and fetuses to examine placental function and fetal development.

During gestation, both ADF and TRF substantially alleviated the metabolic impairments caused by an HFD in obese maternal mice. TRF mice demonstrated enhanced placental nutrient transport and fetal development, associated with reduced endoplasmic reticulum (ER) stress and inflammatory responses. In contrast, ADF markedly intensified placental stress and inflammatory responses, diminished placental nutrient transport efficiency, and consequently induced fetal growth restriction.

Both ADF and TRF during pregnancy significantly mitigated metabolic impairments in obese dams on an HFD. TRF mice demonstrated enhanced placental nutrient transport and fetal development, associated with reduced endoplasmic reticulum (ER) stress and inflammatory responses. In contrast, ADF markedly intensified placental stress and inflammatory responses, diminished placental nutrient transport efficiency, and consequently induced fetal growth restriction.

Major risk factors of cardiovascular disease (CVD) include hypertension, obesity, diabetes mellitus and metabolic syndrome; all of which are considered inflammatory conditions. Women are disproportionately affected by inflammatory conditions, with sex differences emerging as early as adolescence. Hormonal fluctuations associated with reproductive events such as menarche, pregnancy and menopause, are hypothesized to promote a pro-inflammatory state in women. Moreover, women who have experienced inflammatory-type conditions such as polycystic ovarian syndrome (PCOS), gestational diabetes or pre-eclampsia, have a cardiometabolic phenotype that pre-disposes to increased risk of myocardial infarction, stroke and coronary heart disease. Women with no notable CVD risk factors are often relatively protected from CVD pre-menopause; but overtake men in risk of major cardiovascular events when the cardiovascular protective effects of oestrogen begin to wane. Sex differences and female-specific factors have long been considered challenging to study and this has led to an underrepresentation of females in clinical trials and lack of female-specific data from pre-clinical studies. However, there is now a clear prerogative to include females at all stages of research, despite inherent complexities and potential variability in data. This review explores recent advancements in our understanding of CVD in women. We summarise the underlying factors unique to women that can promote CVD risk factors, ultimately contributing to CVD burden and the emerging therapies aimed to combat this.

To evaluate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte ratio (NMR), and other hemogram-derived inflammatory parameters measured in the early second trimester and their association with the risk of gestational diabetes mellitus (GDM).

This case-control study was conducted with 105 women with GDM and 205 healthy pregnant women, matched for maternal age at a 1:2 ratio with the cases at two regional maternity hospitals between January 2021 and August 2022. The inflammatory blood cell indices were tested in the early second trimester, and the patient's characteristics and the course of the pregnancy were analyzed. Logistic regression was used to determine the association between hematological parameters and the risk of GDM. Data were analyzed using SPSS, version 25.0 (SPSS, Chicago, IL).

The final analysis included 310 pregnant women. The GDM group showed a higher pre-pregnancy BMI compared to the healthy controls (p < .01). There was no difference in NMR, PLR, and NLR between the groups (p = .63, .54, and .39, respectively). GDM was only positively associated with MLR (p = .02). After adjusting for potential confounding risk factors including maternal age, parity, and BMI, the multivariate regression analysis showed a higher level of MLR, with a cutoff point of 0.312, was independently associated with the risk of GDM (OR = 2.15, 95%CI 1.51-4.31, p = .03). However, ROC analysis showed that the AUC value of MLR was poor (0.670).

We found that MLR, an inflammatory combined index derived from whole blood counts, may potentially serve as a predictor of GDM in the early second trimester.

Gestational diabetes mellitus is an endocrine and metabolic disorder that appears for the first time during pregnancy and causes varying degrees of short- and/or long-term effects on the mother and child. The etiology of the disease is currently unknown and isobaric tags for relative and absolute quantitation proteomics approach, the present study attempted to identify potential proteins in placental tissues that may be involved in the pathogenesis of GDM and adverse foetal pregnancy outcomes.

Pregnant women with GDM hospitalised were selected as the experimental group, and pregnant women with normal glucose metabolism as the control group. The iTRAQ protein quantification technology was used to screen the differentially expressed proteins between the GDM group and the normal control group, and the differentially expressed proteins were analysed by GO, KEGG, PPI, etc., and the key proteins were subsequently verified by western blot.

Based on the proteomics of iTRAQ, we experimented with three different samples of placental tissues from GDM and normal pregnant women, and the total number of identified proteins were 5906, 5959, and 6017, respectively, which were similar in the three different samples, indicating that the results were reliable. Through the Wayne diagram, we found that the total number of proteins coexisting in the three groups was 4475, and 91 differential proteins that could meet the quantification criteria were strictly screened, of which 32 proteins were up-regulated and 59 proteins were down-regulated. By GO enrichment analysis, these differential proteins are widely distributed in extracellular membrane-bounded organelle, mainly in extracellular exosome, followed by intracellular vesicle, extracellular organelle. It not only undertakes protein binding, protein complex binding, macromolecular complex binding, but also involves molecular biological functions such as neutrophil degranulation, multicellular organismal process, developmental process, cellular component organization, secretion, regulated exocytosis. Through the analysis of the KEGG signaling pathway, it is found that these differential proteins are mainly involved in HIF-1 signaling pathway, Glycolysis/Gluconeogenesis, Central carbon metabolism in cancer, AMPK signaling pathway, Proteoglycans in cancer, Protein processing in endoplasmic reticulum, Thyroid cancer, Alcoholism, Glucagon signaling pathway.

This preliminary study helps us to understand the changes in the placental proteome of GDM patients, and provides new insights into the pathophysiology of GDM.

Gestational diabetes mellitus (GDM) is known to be associated with certain respiratory impairments in offspring. However, the specific association between maternal GDM and childhood lung function remains unclear. We examined the association of maternal glycemia, as measured by oral glucose tolerance test (OGTT) values, with childhood lung function outcomes in a birth cohort.

A follow-up study was conducted with 889 children aged 6 years whose mothers underwent a 75-g OGTT between 24 and 28 weeks of gestation. After adjusting for prenatal and postnatal factors, multivariable regression models were used to evaluate the relationship between maternal glycemia and offspring lung function.

In total, 10.7% of the offspring were exposed to maternal GDM. Maternal GDM significantly reduced the z score of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25-75% of FVC in children, with more pronounced effects in female offspring. Maternal 1- and 2-h post-OGTT glucose z scores and the sum of those z scores, but not those for fasting glucose, were inversely associated with several measures of children's lung function. Additionally, maternal GDM increased the risk of impaired lung function in children (odds ratio 2.64; 95% CI, 1.10-5.85), defined as an FVC <85% of the predicted value. There were no significant associations with FEV1/FVC.

Maternal hyperglycemia was negatively associated with lung function in children, particularly among girls. Further studies are warranted to elucidate the underlying mechanisms of this association and to explore potential interventions to mitigate its effects.

Gestational diabetes mellitus (GDM) is the first spontaneous hyperglycemia during pregnancy. Early diagnosis and intervention are important for the management of the disease. This study compared and analyzed the proteins of total plasma exosomes (T-EXO) and placental-derived exosomes (PLAP-EXO) in pregnant women who subsequently developed GDM (12-16 weeks), GDM patients (24-28 weeks) and their corresponding controls to investigate the pathogenesis and biomarkers of GDM associated with exosomes. The exosomal proteins were extracted and studied by proteomics approach, then bioinformatics analysis was applied to the differentially expressed proteins (DEPs) between the groups. At 12-16 and 24-28 weeks of gestation, 36 and 21 DEPs were identified in T-EXO, while 34 and 20 DEPs were identified in PLAP-EXO between GDM and controls, respectively. These proteins are mainly involved in complement pathways, immunity, inflammation, coagulation and other pathways, most of them have been previously reported as blood or exosomal proteins associated with GDM. The findings suggest that the development of GDM is a progressive process and that early changes promote the development of the disease. Maternal and placental factors play a key role in the pathogenesis of GDM. These proteins especially Hub proteins have the potential to become predictive and diagnostic biomarkers for GDM.