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Background Gestational Diabetes Mellitus (GDM) is one of the most common medical complications during pregnancy. In the Gulf region, the prevalence of GDM is higher than in other parts of the world. Thus, there is a need for the early detection of GDM to avoid critical health conditions in newborns and post-pregnancy complexities of mothers. Methods In this article, we propose a machine learning (ML)-based techniques for early detection of GDM. For this purpose, we considered clinical measurements taken during the first trimester to predict the onset of GDM in the second trimester. Results The proposed ensemble-based model achieved high accuracy in predicting the onset of GDM with around 89% accuracy using only the first trimester data. We confirmed biomarkers, i.e., a history of high glucose level/diabetes, insulin and cholesterol, which align with the previous studies. Moreover, we proposed potential novel biomarkers such as HbA1C %, Glucose, MCH, NT pro-BNP, HOMA-IR- (22.5 Scale), HOMA-IR- (405 Scale), Magnesium, Uric Acid. C-Peptide, Triglyceride, Urea, Chloride, Fibrinogen, MCHC, ALT, family history of Diabetes, Vit B12, TSH, Potassium, Alk Phos, FT4, Homocysteine Plasma LC-MSMS, Monocyte Auto. Conclusion We believe our findings will complement the current clinical practice of GDM diagnosis at an early stage of pregnancy, leading toward minimizing its burden on the healthcare system.Source code is available in GitHub at: https://github.com/H-Zaky/GD.git

The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother—child pairs from the prospective \"Rhea\" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (≥0.8 μg/L) were inversely associated with children's general cognitive score [mean change: —6.1 points (95 % CI — 12; —0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI —0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 μg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out.

Background Gestational diabetes mellitus (GDM) is a common metabolic disorder characterized by hyperglycemia that is first detected during pregnancy, which is not overt diabetes. GDM poses a substantial risk for prenatal and postnatal adverse outcomes affecting both the mother and the offspring. These complications include, but are not limited to, fetal macrosomia, shoulder dystocia, respiratory distress, neonatal hypoglycemia, type 2 diabetes (T2D), and cardiovascular diseases. Screening for GDM typically occurs between 24 and 28 weeks of gestation, a timing that is considered late and may increase the risk of all the adverse outcomes associated with GDM. Treatment and prevention strategies are not standardized globally, may be suboptimal, and are often initiated after a diagnosis has been made. Therefore, our primary goal was to identify DNA methylation signatures specific to GDM to understand its underlying mechanisms. Methods We conducted genome-wide DNA methylation profiling for normal and GDM pregnant women across the three trimesters of pregnancy in the discovery cohort. DNA methylation levels were measured using the Infinium MethylationEPIC v2.0 BeadChip. Subsequently, our differentially methylated sites were validated in a second cohort. Furthermore, we performed downstream analyses, including KEGG pathway and Gene Ontology enrichment analysis, trait enrichment analysis, and gene expression regulation analysis for the validated differentially methylated sites identified in the second and third trimesters. Results In this study, we uncovered and validated new DNA methylation signatures that may significantly influence the expression of genes associated with GDM. Furthermore, we discovered new genes ( RSL1D1 , HOXD4 , and MROH6 ) that may play a role in GDM and might be related to the risk of developing T2D and cardiovascular disease later in life. Trait analysis of the differentially methylated probes revealed that lifestyle and environmental factors are associated with the observed DNA methylation signatures in GDM. Conclusions We conclude that DNA methylation changes during pregnancy might not fully explain GDM pathogenesis but can reflect population-specific environmental and behavioral factors before and during pregnancy. Some of these discovered CpG sites might regulate previously reported genes linked to GDM and diabetes, highlighting shared and distinct epigenetic mechanisms across populations.

Background: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. Objectives: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother—child study. Methods: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006—2010. Maternal diet was estimated through food-frequency questionnaires. Results: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was —132 g (95% CI: —207, —56); the corresponding difference for head circumference was —0.33 cm (95% CI: —0.61, —0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. Conclusions: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. If confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.

Pregnancy is a dynamic physiological process involving significant hormonal, immune, and metabolic changes to support fetal growth and development. This study investigates the changes in salivary microbiome and biochemical markers from the second to the third trimester of pregnancy. Saliva samples were collected from 45 pregnant women enrolled in the Qatar Birth Cohort study at two time points (second and third trimesters). DNA was extracted and subjected to 16S rRNA gene sequencing using Oxford Nanopore Technology. Microbial diversity and taxonomic analyses were performed, along with correlation analyses between microbial abundance and clinical parameters. Biochemically, significant increases in BMI, pulse rate, HbA1c, LDL, total cholesterol, and triglycerides were observed in the third trimester compared to the second. Microbial diversity analysis revealed significant changes in microbial richness and composition. Taxonomy analysis showed a significant 3-fold increase in Bacteroidota. Also, a significant decline in Selenomonas and a significant increase in Veillonella , specifically Veillonella dispar and Veillonella atypica , as well as an increase in Granulicatella were observed in the third trimester, along with a significant decrease in Streptococcus sanguinis . Correlation analysis during the second trimester revealed positive associations between BMI, cholesterol, LDL, and Selenomonas , and negative correlations with Streptococcus and Gemella . In the third trimester, BMI was negatively correlated with Campylobacter , glucose levels were negatively correlated with Neisseria , and triglyceride levels were negatively correlated with Prevotella . These findings highlight significant biochemical and microbial shifts during pregnancy, underscoring the importance of monitoring oral health and metabolic changes in pregnant women.

Background The latest scientific reports raise concerns about the rapidly increasing burden of chronic diseases in the state of Qatar. Pregnant Qatari women often confront complications during pregnancy including gestational diabetes, hypertension, abortion and stillbirth. The investigation of early life environmental, genetic, nutritional and social factors that may affect lifelong health is of great importance. Birth cohort studies offer a great opportunity to address early life hazards and their possible long lasting effects on health. Methods/design The Qatari Birth Cohort study is the first mother-child cohort study in the Middle East Area that aims to assess the synergetic role of environmental exposure and genetic factors in the development of chronic disease and monitor woman and child health and/or obstetric characteristics with high prevalence. The present manuscript describes the recruitment phase of the study (duration: 2 years; expected number: 3000 families), where the pregnant Qatari women and their husbands are being contacted before the 15th week of gestation at the Primary Health Care Centers. The consented participants are interviewed to obtain information on several factors (sociodemographic characteristics, dietary habits, occupational/environmental exposure) and maternal characteristics are assessed based on anthropometric measurements, spirometry, and blood pressure. Pregnant women are invited to provide biological samples (blood and urine) in each trimester of their pregnancy, as well as cord blood at delivery. Fathers are also asked to provide biological samples. Discussion The present study provides invaluable insights into a wide range of early life factors affecting human health. With a geographical focus on the Middle East, it will be a resource for information to the wider scientific community and will allow the formulation of effective policies with a primary focus on public health interventions for maternal and child health.

Syndecan-1 forms complexes with growth factors and their cognate receptors in the cell membrane. We have previously reported a tubulin-mediated translocation of syndecan-1 to the nucleus. The transport route and functional significance of nuclear syndecan-1 is still incompletely understood. Here we investigate the sub-cellular distribution of syndecan-1, FGF-2, FGFR-1 and heparanase in malignant mesenchymal tumor cells, and explore the possibility of their coordinated translocation to the nucleus. To elucidate a structural requirement for this nuclear transport, we have transfected cells with a syndecan-1/EGFP construct or with a short truncated version containing only the tubulin binding RMKKK sequence. The sub-cellular distribution of the EGFP fusion proteins was monitored by fluorescence microscopy. Our data indicate that syndecan-1, FGF-2 and heparanase co-localize in the nucleus, whereas FGFR-1 is enriched mainly in the perinuclear area. Overexpression of syndecan-1 results in increased nuclear accumulation of FGF-2, demonstrating the functional importance of syndecan-1 for this nuclear transport. Interestingly, exogenously added FGF-2 does not follow the route taken by endogenous FGF-2. Furthermore, we prove that the RMKKK sequence of syndecan-1 is necessary and sufficient for nuclear translocation, acting as a nuclear localization signal, and the Arginine residue is vital for this localization. We conclude that syndecan-1 and FGF-2, but not FGFR-1 share a common transport route and co-localize with heparanase in the nucleus, and this transport is mediated by the RMKKK motif in syndecan-1. Our study opens a new perspective in the proteoglycan field and provides more evidence of nuclear interactions of syndecan-1.

Syndecans are proteoglycans whose core proteins have a short cytoplasmic domain, a transmembrane domain and a large N-terminal extracellular domain possessing glycosaminoglycan chains. Syndecans are involved in many important cellular processes. Our recent publications have demonstrated that syndecan-1 translocates into the nucleus and hampers tumor cell proliferation. In the present study, we aimed to investigate the role of syndecan-1 in tumor cell adhesion and migration, with special focus on the importance of its distinct protein domains, to better understand the structure-function relationship of syndecan-1 in tumor progression. We utilized two mesenchymal tumor cell lines which were transfected to stably overexpress full-length syndecan-1 or truncated variants: the 78 which lacks the extracellular domain except the DRKE sequence proposed to be essential for oligomerization, the 77 which lacks the whole extracellular domain, and the RMKKK which serves as a nuclear localization signal. The deletion of the RMKKK motif from full-length syndecan-1 abolished the nuclear translocation of this proteoglycan. Various bioassays for cell adhesion, chemotaxis, random movement and wound healing were studied. Furthermore, we performed gene microarray to analyze the global gene expression pattern influenced by syndecan-1. Both full-length and truncated syndecan-1 constructs decrease tumor cell migration and motility, and affect cell adhesion. Distinct protein domains have differential effects, the extracellular domain is more important for promoting cell adhesion, while the transmembrane and cytoplasmic domains are sufficient for inhibition of cell migration. Cell behavior seems to depend also on the nuclear translocation of syndecan-1. Many genes are differentially regulated by syndecan-1 and a number of genes are actually involved in cell adhesion and migration. Our results demonstrate that syndecan-1 regulates mesenchymal tumor cell adhesion and migration, and different domains have differential effects. Our study provides new insights into better understanding of the role of syndecans in tumor progression.

Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk. We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes. MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother-child cohort in Crete, Greece, in 2007-2008. Residential BTHM water concentrations were estimated during pregnancy using tap water analyses and modeling. Questionnaires on water related habits were used to estimate BTHM exposure from all routes. Associations between BTHM and MN frequency were estimated using negative binomial regression. BTHM concentrations in residential tap water during pregnancy ranged from 0.06 to 7.1 μg/L. MN frequency in maternal binucleated lymphocytes was found to increase with BTHM concentrations in residential water for exposure during the first [rate ratio (RR) for 1 μg/L=1.05; 95% CI: 1.00, 1.11] and second trimesters (RR for 1 μg/L=1.03; 95% CI: 1.00, 1.06), and through all routes of BTHM exposure during the first trimester (RR for 1 μg/week=3.14; 95% CI: 1.16, 8.50). These findings suggest that exposure to BTHM may increase the frequency of MN in maternal binucleated lymphocytes.

Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006-2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of -129 g (95% CI: -233, -25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (-248 g; 95% CI: -405, -92 g) compared with those with high intake (-58 g; 95% CI: -206, 90 g). Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.