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Background: Macrosomia at birth is associated with maternal hyperglycemia and leads to subsequent susceptibility to obesity, abnormal glucose metabolism, hypertension, and dyslipidemia in offspring. Epigenetic reprogramming has been reported to be involved in the development of human diseases caused by suboptimal environmental or nutritional factors. The study was aiming to explore epigenetic mechanism influences on macrosomic infants exposed to intrauterine hyperglycemia. We performed a genome-wide analysis of DNA methylation in cord blood from macrosomic infants born to women with gestational diabetes in order to identify genes related to fetal growth or early adipose tissue development.Methods: To analyze the epigenetic patterns in umbilical cord blood in gestational diabetes mellitus (GDM), we collected umbilical cord blood from women with GDM (mean pregestational BMI of 24.4 kg/m2 and mean neonatal birth weight of 4366 g) and normal glucose-tolerant women (mean pregestational BMI of 19.8 kg/m2 and mean neonatal birth weight of 3166 g). Differentially methylated genes in the GDM group were identified using the Infinium HumanMethylation450 BeadChip array.Results: A total of 1251 genes were differentially methylated compared to the controls (p < .01). The methylation microarray data showed that two specific CpG sites (cg12604331 and cg08480098) in the gene body of ARHGEF11 were significantly hypomethylated in the cord blood in macrosomic infants. Altered DNA methylation levels of ARHGEF11 were negatively correlated with glucose levels and neonatal birth weight.Conclusions: Exposure to adverse intrauterine environments can alter fetal development, such as by affecting the nutritional status of the fetus. Such exposure can also result in significant epigenetic modifications, including DNA methylation, which could serve as a potential marker for nutrition and metabolic conditions at the neonatal stage or even in the adult. [ABSTRACT FROM AUTHOR]

Purpose: Gestational diabetes mellitus (GDM) may share similar mechanisms with type 2 diabetes and obesity. In the current study, we aimed to verify twenty genes reported to be associated with type 2 diabetes and obesity in the Chinese GDM population.Methods: Pregnant women aged 20-49 years at 24-28 gestational weeks were recruited and 556 cases and 445 controls were enrolled in the study. The genotyping of single nucleotide polymorphisms (SNPs) was performed on peripheral blood samples.Results: We discovered that GDM was associated with rs945508 (OR = 1.368, 95% CI = 1.080-1.732, p = .009), rs10804591 (OR = 1.446, 95% CI = 1.192-1.754, p < .001), rs10245353 (OR = 1.204, 95% CI = 1.006-1.441, p = .043) and rs1552224 (OR = 1.451, 95% CI = 1.071-1.964, p = .016).Conclusions: We found that four SNPs associated with type 2 diabetes and obesity may also increase the risk of developing GDM in the Chinese population. Among these SNPs, we report for the first time that rs945508 in ARHGEF11, rs10804591 in PLXND1 and rs10245353 in NFE2L3 were associated with GDM. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p<0.05), and these differences were more pronounced in the maternal section of the placenta and the syncytiotrophoblast of villi. In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312) (p<0.001) and lower IRS-1 (p<0.05) as well as pAkt proteins (p<0.01). The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT. We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia. The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM. [ABSTRACT FROM AUTHOR]

Aims/Hypothesis: Gestational diabetes mellitus (GDM) is increasing rapidly worldwide. Previous animal models were established to study consequences of offspring after exposure to severe intrauterine hyperglycemia. In this study we are aiming to characterize the blood pressure levels and renal function of male offspring obtained from diabetic mothers with moderate hyperglycemia. Methods: We established a rat model with moderate hyperglycemia after pregnancy by a single intraperitoneal injection of streptozotocin (STZ). The male offspring were studied and fed with either normal diet or high salt diet after weaning. Arterial pressure and renal function were measured. Results: Arterial pressure of male offspring increased from 12 weeks by exposure to intrauterine moderate hyperglycemia. At 20 weeks, high salt diet accelerated the blood pressure on diabetic offspring compared to diabetic offspring fed with normal diet. We found offspring exposed to intrauterine moderate hyperglycemia had a trend to have a higher creatinine clearance rate and significant increase of urinary N-acetyl-β-D-glucosaminidase (NAG) excretion indicating an early stage of nephropathy progression. Conclusions/Interpretation: We observed the high blood pressure level and early renal dysfunction of male offspring obtained from diabetic mothers with moderate hyperglycemia. Furthermore, we investigated high salt diet after weaning on offspring exposed to intrauterine hyperglycemia could exacerbate the blood pressure and renal function. Renin angiotensin system (RAS) plays an important role in hypertension pathogenesis and altered gene expression of RAS components in offspring with in utero hyperglycemia exposure may account for the programmed hypertension. Therefore, our study provides evidence “fetal programming” of maternal diabetes is critical for metabolic disease development. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin (Hb) measurement is a standard test among pregnant women during the first perinatal visit that is used to evaluate physical status and anemia. However, studies focusing on Hb levels and pregnancy outcomes are scarce. This study aimed to determine whether Hb levels in early pregnancy were associated with the risk of gestational diabetes mellitus (GDM), pre-eclampsia (PE) and preterm birth.Methods: A hospital-based retrospective study was conducted among 21,577 singleton, non-smoking pregnancies between June 2013 and January 2015. The demographic data and medical information of each participant were collected individually through questionnaires and patient medical records. Odds ratios were generated using a multivariate logistic regression analysis to evaluate the relative risk of GDM, PE and preterm birth continuously and across different hemoglobin ranges in the overall population and in women from different pre-pregnancy body mass index (BMI) categories, respectively. The level of statistical significance was set at 0.05.Results: (1) For women who were underweight, normal-weight, overweight and obese, early pregnancy Hb levels were 127.8 ± 10.1 g/L, 129.6 ± 9.7 g/L, 132.2 ± 9.5 g/L and 133.4 ± 9.4 g/L, respectively. (2) Women with GDM and PE had significantly increased Hb levels during early pregnancy compared with controls, whereas women with preterm birth processed significantly decreased Hb levels. (3) After adjusting for confounders, the risks for GDM and PE increased with high maternal Hb (OR: 1.27 for Hb 130-149; OR: 2.06 for Hb ≥ 150 g/L), and the risk for preterm birth decreased with high maternal Hb (OR: 1.30 for Hb 130-149; OR: 2.38 for Hb ≥ 150 g/L) and increased with low maternal Hb (OR: 1.41 for Hb <  110 g/L). Among women whose BMI was < 24 kg/m2, high GDM (OR: 1.27 for Hb 130-149; OR: 1.84 for Hb ≥ 150 g/L) and low preterm rates (OR: 0.77 for Hb 130-149; OR: 0.23 for Hb ≥ 150 g/L) were observed with high Hb, whereas in women whose BMI was ≥24 kg/m2, only high GDM rates were observed with Hb > 150 g/L (OR: 2.33).Conclusion: These findings suggest that Hb levels during early pregnancy play a role in predicting the risk of GDM, PE and preterm birth. [ABSTRACT FROM AUTHOR]

This study aimed at evaluating the predictive effects of early pregnancy lipid profiles and fasting glucose on the risk of gestational diabetes mellitus (GDM) in patients stratified by prepregnancy body mass index (p-BMI) and to determine the optimal cut-off values of each indicator for different p-BMI ranges. A retrospective system cluster sampling survey was conducted in Beijing during 2013 and a total of 5,265 singleton pregnancies without prepregnancy diabetes were included. The information for each participant was collected individually using questionnaires and medical records. Logistic regression analysis and receiver operator characteristics analysis were used in the analysis. Outcomes showed that potential markers for the prediction of GDM include early pregnancy lipid profiles (cholesterol, triacylglycerols, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratios [LDL-C/HDL-C], and triglyceride to high-density lipoprotein cholesterol ratios [TG/HDL-C]) and fasting glucose, of which fasting glucose level was the most accurate indicator. Furthermore, the predictive effects and cut-off values for these factors varied according to p-BMI. Thus, p-BMI should be a consideration for the risk assessment of pregnant patients for GDM development. [ABSTRACT FROM AUTHOR]

This study aimed at evaluating the predictive effects of early pregnancy lipid profiles and fasting glucose on the risk of gestational diabetes mellitus (GDM) in patients stratified by prepregnancy body mass index (p-BMI) and to determine the optimal cut-off values of each indicator for different p-BMI ranges. A retrospective system cluster sampling survey was conducted in Beijing during 2013 and a total of 5,265 singleton pregnancies without prepregnancy diabetes were included. The information for each participant was collected individually using questionnaires and medical records. Logistic regression analysis and receiver operator characteristics analysis were used in the analysis. Outcomes showed that potential markers for the prediction of GDM include early pregnancy lipid profiles (cholesterol, triacylglycerols, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratios [LDL-C/HDL-C], and triglyceride to high-density lipoprotein cholesterol ratios [TG/HDL-C]) and fasting glucose, of which fasting glucose level was the most accurate indicator. Furthermore, the predictive effects and cut-off values for these factors varied according to p-BMI. Thus, p-BMI should be a consideration for the risk assessment of pregnant patients for GDM development. [ABSTRACT FROM AUTHOR]

Background: The study aimed to evaluate whether exercise intervention can be applied to pregnant women with gestational diabetes mellitus (GDM) for controlling gestational weight gain (GWG) and combating GDM-related outcomes.Methods: Retrospective six months analysis of 14,168 single pregnant women without diabetes from 15 hospitals in Beijing in 2013. Each participant's demographic data, interventions condition and medical information were collected individually by questionnaires and relying on medical records. The level of statistical significance was set equal to 0.05.Results: 2750 (19.4%) pregnant women were diagnosed with GDM, 74.9% of them received exercise intervention during pregnancy, and the starting time was 25.8 ± 3.7 gestational weeks. Women with GDM with exercise intervention (GDM-E) had the lowest BMI increase during late and mid-pregnancy than women with GDM without exercise intervention (GDM-nE) (2.05 ± 1.32 kg/m(2) vs. 2.40 ± 1.30 kg/m(2), p < 0.01) and non-GDM women (2.05 ± 1.32 kg/m(2) vs. 2.77 ± 1.21 kg/m(2), p < 0.01). Moreover, GDM-E group experienced a significantly lower risk of preterm birth (5.58% vs. 7.98%, p < 0.001), low birth weight (1.03% vs. 2.06 %, p < 0.001) and macrosomia (9.51 % vs. 11.18%, p > 0.05) than GDM-nE group. After including dietary factors in the analysis, women with GDM without either dietary or exercise intervention (GDM-nDnE) had the highest risk of preterm birth(OR = 1.64, 95 % CI, 1.14-2.36), while women with GDM with dietary intervention only (GDM-DnE) had the highest risk of low birth weight (OR = 3.10, 95 % CI, 1.23-7.81). However, women with GDM with both dietary and exercise intervention had the lowest rate of macrosomia.Conclusion: Exercise intervention is a suitable non-invasive therapeutic option that can be readily applied to manage weight gain and improve pregnancy outcomes in women with GDM. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the importance and usefulness of fasting plasma glucose (FPG) in the first trimester in predicting adverse pregnancy outcomes.Methods: A retrospective study of 22,398 singleton pregnancies was conducted. Participants were divided into subgroups according to first-trimester FPG (low FPG, FPG < 5.1 mmol/L; medium FPG, 5.1 mmol/L ≤ FPG < 5.6 mmol/L; high FPG, 5.6 ≤ FPG < 7.0 mmol/L) and oral glucose tolerance test(OGTT) results (normal and abnormal) during pregnancy. Patient characteristics and risk of adverse pregnancy outcomes were compared. Then, the whole population of women with abnormal OGTT served as a reference, and the relative risks of maternal and neonatal complications in normal OGTT women were analyzed by categorical analyses and logistic regression. Subgroup analyses were performed according to pre-pregnancy body mass index (BMI).Results: The frequency of adverse pregnancy outcomes increased with increasing FPG levels during the first trimester, regardless of OGTT results. High FPG + Abnormal OGTT had the worst outcome. Compared to the whole population of women with abnormal OGTT, Normal OGTT + Medium FPG showed the same risk of PIH and macrosomia. Normal OGTT + High FPG showed the same risk of PIH, macrosomia as well as LGA and preterm birth. Additionally, Normal OGTT + Medium FPG + BMI ≥ 24 kg/m2 showed significantly higher risk of PIH (OR = 1.867, 1.245-2.800), macrosomia (OR = 1.748, 1.304-2.344) and LGA (OR = 1.274, 1.019-1.593). Furthermore, the OR value for PIH was 3.759 (1.680-8.412) in Normal OGTT + High FPG + BMI ≥ 24 kg/m2 compared to women with abnormal OGTT.Conclusions: First-trimester FPG values can help identify women at increased risk for adverse pregnancy outcomes. Increased attention and management should be given to women with early pregnancy FPG ≥ 5.10 mmol/L despite a normal OGTT, especially if their BMI ≥ 24 kg/m2. [ABSTRACT FROM AUTHOR]

Background: Anaemia in pregnant women is a public health problem, especially in developing countries. The aim of this study was to assess the prevalence and related risk factors of anaemia during pregnancy in a large multicentre retrospective study (n = 44,002) and to determine the adverse pregnancy outcomes in women with or without anaemia. Methods: The study is a secondary data analysis of a retrospective study named "Gestational diabetes mellitus Prevalence Survey (GPS) study in China". Structured questionnaires were used to collect socio-demographic characteristics, haemoglobin levels and pregnancy outcomes from all the participants. Anaemia in pregnancy is defined as haemoglobin < 110 g/L. We used SPSS software to assess the predictors of anaemia and associated adverse pregnancy outcomes. Results: The overall prevalence of anaemia was 23.5%. Maternal anaemia was significantly associated with maternal age ≥ 35 years (AOR = 1.386), family per capita monthly income< 1000 CNY (AOR = 1.671), rural residence (AOR = 1.308) and pre-pregnancy BMI < 18.5 kg/m2 (AOR = 1.237). Adverse pregnancy outcomes, including GDM, polyhydramnios, preterm birth, low birth weight (< 2500 g), neonatal complications and NICU admission, increased significantly (P < 0.001) in those with anaemia than those without. Conclusions: The results indicated that anaemia continues to be a severe health problem among pregnant women in China. Anaemia is associated with adverse pregnancy outcomes. Pregnant women should receive routine antenatal care and be given selective iron supplementation when appropriate. [ABSTRACT FROM AUTHOR]