BackgroundAspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) has been reported affect the risk of type 2 diabetes (T2DM), but it is uncertain if it has relationship with gestational diabetes mellitus (GDM).ObjectivesOur study aimed to investigate the association between AST/ALT ratio in the first trimester and the risk of subsequent development of GDM.MethodThis prospective cohort study enrolling 870 pregnant women, 204 pregnant women with missing data or liver diseases were excluded, 666 pregnant women were included in this study containing 94 GDM women. Blood samples were collected in the first trimester. Univariate analysis and multivariate logistic regression were used to evaluate the association between AST/ALT and GDM. Nomogram was established based on the results of multivariate logistic analysis. Receiver Operating Characteristic (ROC) curves and calibration curves were used to evaluate the predictive ability of this nomogram model for GDM. Decision curve analysis (DCA) was used to examine the clinical net benefit of predictive model.ResultsAST/ALT ratio (RR:0.228; 95% CI:0.107-0.488) was associated with lower risk of GDM after adjusting for confounding factors. Indicators used in nomogram including AST/ALT, maternal age, preBMI, waist circumference, glucose, triglycerides, high density lipoprotein cholesterol and parity. The area under the ROC curve (AUC) value of this predictive model was 0.778, 95% CI (0.724, 0.832). Calibration curves for GDM probabilities showed acceptable agreement between nomogram predictions and observations. The DCA curve demonstrated a good positive net benefit in the predictive model.ConclusionsThe early AST/ALT level of pregnant women negatively correlated with the risk of GDM. The nomogram including AST/ALT at early pregnancy shows good predictive ability for the occurrence of GDM.

Genome-wide DNA methylation profiling have been used to find maternal CpG sites related to the occurrence of gestational diabetes mellitus (GDM). However, none of these differential sites found has been verified in a larger sample. Here, our aim was to evaluate whether first trimester changes in target CpG sites in the peripheral blood of pregnancy women predict subsequent development of GDM. This nested case–control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites of 80 GDM cases and 80 matched healthy controls during the early pregnancy (10–15 weeks) were assessed using MethylTarget sequencing. The best cut-off level for methylation of CpG site was determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at another 6 CpG sites were significantly lower (FDR < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for the occurrence of GDM. After adjusting for possible confounders, the hypermethylation status of CpG site 68167324 (OR = 3.168, 1.038–9.666) and 24837915 (OR = 5.232, 1.659–16.506) was identified as more strongly associated with GDM; meanwhile, the hypermethylation of CpG site 157130156 (OR = 0.361, 0.135–0.966) and 89438648 (OR = 0.206, 0.065–0.655) might indicate lower risk of GDM. The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester may be associated with GDM pathogenesis, and has potential as a predictor of GDM.

(1) Background: Pregnancy-induced hypertension (PIH) is associated with obvious microbiota dysbiosis in the third trimester of pregnancy. However, the mechanisms behind these changes remain unknown. Therefore, this study aimed to explore the relationship between the gut microbiome in early pregnancy and PIH occurrence. (2) Methods: A nested case–control study design was used based on the follow-up cohort. Thirty-five PIH patients and thirty-five matched healthy pregnant women were selected as controls. The gut microbiome profiles were assessed in the first trimester using metagenomic sequencing. (3) Results: Diversity analyses showed that microbiota diversity was altered in early pregnancy. At the species level, eight bacterial species were enriched in healthy controls: Alistipes putredinis, Bacteroides vulgatus, Ruminococcus torques, Oscillibacter unclassified, Akkermansia muciniphila, Clostridium citroniae, Parasutterella excrementihominis and Burkholderiales bacterium_1_1_47. Conversely, Eubacterium rectale, and Ruminococcus bromii were enriched in PIH patients. The results of functional analysis showed that the changes in these different microorganisms may affect the blood pressure of pregnant women by affecting the metabolism of vitamin K2, sphingolipid, lipid acid and glycine. (4) Conclusion: Microbiota dysbiosis in PIH patients begins in the first trimester of pregnancy, and this may be associated with the occurrence of PIH. Bacterial pathway analyses suggest that the gut microbiome might lead to the development of PIH through the alterations of function modules.

Background: Fetal macrosomia is defined as birthweight≧4000g and causes harm to pregnant women and infants. Studies reported that maternal intestinal microbiome plays a key role in the establishment, growth and development of fetal intestinal flora; however, the relationship between maternal gut microbiota and macrosomia remains unclear. Our study aimed to investigate whether maternal gut microbiome is associated with macrosomia and explored the potential microbiome biomarkers at early pregnancy to prevent macrosomia .Methods: We conducted a nested case control study based on an early pregnancy cohort (ChiCTR1900020652) in Maternity and Child Health Hospital of Hunan Province, fecal samples of 93 women(31 delivered macrosomia as case group and 62 delivered normal birth weight newborns as the control group) collected and included in this study. And we performed metagenomic analysis to compare the composition and function of gut microbiome between cases and controls. Correlation analysis was used to explore the association of differential species with differential functional pathways and clinical parameters.Results: There are more phylum Bacteroidetes, order Bacteroidales and Burkholderiales, class Betaproteobacteria and Bacteroidia and Bacteroides ovatus in the intestinal flora of macrosomias’mothers compared with fetuses with normal birth weight. Functional pathways of gut microbiome including gondoate biosynthesis (anaerobic), L-histidine degradation III, cis-vaccenate biosynthesis and mannitol cycle were more abundant in macrosomia group. Significant correlations were discovered between taxa associated in macrosomia and triglycerides. Furthermore, Bacteroidetes (phylum), Bacteroidia (class), Bacteroidales (order) and Bacteroides ovatus were significantly associated with the pathway of gondoate biosynthesis, L−histidine degradation III, cis−vaccenate biosynthesis and Bacteroides ovatus was correlated with mannitol cycle pathway.Conclusions: Maternal gut microbiota may play an important role in the development of macrosomia and can be used as predictors to prevent macrosomia.