The associations of maternal liver biomarkers in early pregnancy with the risk of gestational diabetes mellitus: a prospective cohort study and Mendelian randomization analysis.

Background: Associations of liver function with the risk of gestational diabetes mellitus (GDM) remain unclear. This study aimed to examine the relationship and the potential causality between maternal liver biomarkers and the risk of subsequent GDM, as well as to evaluate the interaction between liver biomarkers and lipids on GDM risk. Methods: In an ongoing Zhoushan Pregnant Women Cohort, pregnant women who finished the first prenatal follow-up record, underwent liver function tests in early pregnancy, and completed the GDM screening were included in this study. Logistic regression models were used to investigate the association, and the inverse-variance weighted method supplemented with other methods of two-sample Mendelian randomization (MR) analysis was applied to deduce the causality. Results: Among 9,148 pregnant women, 1,668 (18.2%) developed GDM. In general, the highest quartile of liver function index (LFI), including ALT, AST, GGT, ALP, and hepatic steatosis index, was significantly associated with an increased risk of GDM (OR ranging from 1.29 to 3.15), especially an elevated risk of abnormal postprandial blood glucose level. Moreover, the causal link between ALT and GDM was confirmed by the MR analysis (OR=1.28, 95%CI:1.05-1.54). A significant interaction between AST/ALT and TG on GDM risk was observed (P interaction = 0.026). Conclusion: Elevated levels of LFI in early pregnancy were remarkably associated with an increased risk of GDM in our prospective cohort. Besides, a positive causal link between ALT and GDM was suggested.

Associations of maternal liver biomarkers in the first trimester with the risk of hypertensive disorders of pregnancy.

This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23-2.41), 1.53-fold (95% Cl: 1.10-2.14), 0.62-fold (95% Cl: 0.43-0.90) and 1.67-fold (95% Cl: 1.05-2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (Pinteraction = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP. Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP.

Breastfeeding, Gestational Diabetes Mellitus, Size at Birth and Overweight/Obesity in Early Childhood.

Background: Breastfeeding appears to reduce the risk of childhood overweight/obesity. However, it remains unclear whether this protective effect persists among high-risk populations. This study aims to investigate the association of breastfeeding with the risk of overweight/obesity in early childhood and whether this association is altered by gestational diabetes mellitus (GDM) or size at birth. Methods: Feeding practices during the first 12 months of age and weight and length at 12-36 months of age were collected. Full breastfeeding includes exclusive and predominant breastfeeding. Children with body mass index (BMI) values greater than 1 standard deviation from the mean of sex- and age-specific BMI were classified as overweight/obese. Multiple generalized estimating equations models were applied to analyze the associations of full breastfeeding duration with overweight/obesity risk. Results: Among all participants (n = 9329), infants with a longer full-breastfeeding duration had a reduced risk of overweight/obesity in early childhood compared with those breastfed for less than one month. Infants exposed to GDM and those born large for gestational age (LGA) had a higher risk of overweight/obesity in early childhood. Among infants of mothers with GDM (n = 1748), infants with full breastfeeding for greater than 6 months (aOR: 0.58; 95% CI: 0.44, 0.78) showed a decreased risk of overweight/obesity in early childhood compared with those breastfed for less than one month. Among LGA infants (n = 1279), infants with full breastfeeding for 3-5 months (aOR: 0.66; 95% CI: 0.57, 0.76) and greater than 6 months (aOR: 0.70; 95% CI: 0.56, 0.88) showed a decreased risk of overweight/obesity in early childhood. Similar results were observed among LGA infants of mothers with GDM. Conclusions: Initiating and prolonging breastfeeding would reduce the risk of overweight/obesity in early childhood, and LGA infants and infants born to mothers with GDM would experience greater benefits.

Ilizarov method and its combined methods in the treatment of long bone defects of the lower extremity: systematic review and meta-analysis.

BACKGROUND: Ilizarov method has become one of primary methods for treating bone defects. Currently, there is growing trend in the application of modified Ilizarov methods (e.g., applying unilateral external fixators or with flap tissue) and its combined methods (e.g., Ilizarov method with antibiotic spacer or internal fixation) to manage bone defects. However, there is a lack of studies with systematical evaluation of the clinical effects of these evolving methods. This study aimed to conduct a systematic review and meta-analysis for overall evaluating the clinical effects on long bone defects of lower extremity in Ilizarov methods and its combined methods. METHODS: Studies were identified in three electronic databases (Pubmed, Embase and Cochrane Library) from the earliest indexing year through November 01, 2022, and relevant data were extracted subsequently. The total number of participants, number of participants with bone unions, bone result or functional result, and related complications including pin infection, pin loosening, pain, refracture, limb discrepancy, malalignment, joint stiffness, recurrent infection, and amputation were extracted in this study. Then, union rate (defined as the proportion of patients who achieved bone unions) and specific complication incidence rate (defined as the proportion of patients who experienced specific complication) were pooled estimated respectively. Relative risk (RR) was used for comparing the clinical effects among various Ilizarov technique. RESULTS: Sixty-eight case series studies, 29 comparative studies, and 3 randomized clinical trials were finally included. The union rate of Ilizarov methods was 99.29% (95% CI: 98.67% ~ 99.86%) in tibial defects and 98.81% (95% CI: 98.81% ~ 100.00%) in femoral defects. The union rate of Ilizarov method with antibiotic spacer and intramedullary nail in tibial defects was 99.58% (95% CI: 98.05% ~ 100.00%) and 95.02% (95% CI: 87.28% ~ 100.00%), respectively. Compared to the Ilizarov methods, the union rate of the Ilizarov method with antibiotic spacer in tibial defects increased slightly (RR = 1.02, 95% CI: 1.01 ~ 1.04). Meanwhile, compared to Ilizarov methods, we found lower excellent rate in bone result in Ilizarov method with antibiotic spacer, with the moderate to high heterogeneity. Compared to the Ilizarov method, lower rate of pin infection, higher rate of recurrent infection and amputation were observed in Ilizarov method with intramedullary nail, however, the findings about the comparison of pin infection and recurrent infection between the two groups were presented with high degree of statistical heterogeneity. CONCLUSION: Our study confirmed the reliable treatment of Ilizarov methods and its combined technique on long bone defects, and founded there were significant differences on some complications rate between Ilizarov methods and its combined technique. However, the findings need to be confirmed by further studies.

Association of 25-Hydroxyvitamin D with Preterm Birth and Premature Rupture of Membranes: A Mendelian Randomization Study.

Low vitamin D (VitD) level is a risk factor for preterm birth (PTB), but the results of previous studies remained inconsistent, which may be influenced by the confounding factors and different types of PTB. We performed Mendelian randomization (MR) to uncover the association of 25-hydroxyvitamin D (25(OH)D) with PTB, premature rupture of membranes (PROM), and preterm premature rupture of membranes (PPROM). This study was conducted in Zhoushan Maternal and Child Health Hospital, Zhejiang, from August 2011 to March 2022. Plasma 25(OH)D levels in three trimesters of pregnancy were measured. We conducted an MR analysis utilizing a genetic risk score (GRS) approach, which was based on VitD-associated single-nucleotide polymorphisms. The prospective cohort study included 3923 pregnant women. The prevalence of PTB, PROM, and PPROM were 6.09%, 13.18%, and 1.33%, respectively. Compared to those without vitamin D deficiency (VDD), only vaginally delivering pregnant women with VDD had a 2.69 (1.08-6.68) times risk of PTB. However, MR analysis did not support the association. One-unit higher GRS was not associated with an increased risk of PTB, regardless of the trimesters (OR [95% CI]: 1.01 [0.93-1.10], 1.06 [0.96-1.18], and 0.95 [0.82-1.10], respectively). When further taking PROM and PPROM as the outcomes, the MR analysis also showed no consistent evidence of a causal effect of VitD levels on the risk of them. Our MR analyses did not support a causal effect of 25(OH)D concentrations in the three trimesters on PTB, PROM, and PPROM.

The Association of Vitamin D during Pregnancy and mRNA Expression Levels of Inflammatory Factors with Preterm Birth and Prelabor Rupture of Membranes.

The aim of this study was to elucidate the association between vitamin D (VD) and the risk for preterm birth (PTB) and prelabor rupture of membranes (PROM). This study included two parts, with a cohort study and a case-control study. Plasma 25-hydroxyvitamin vitamin D [25(OH)D] levels in three trimesters in the cohort study and maternal 25(OH)D before delivery in the case-control study were measured. Quantitative real-time PCR was used to detect relative mRNA expression levels of the inflammatory factors associated with pyroptosis in peripheral blood mononuclear cell (PBMC), placenta and fetal membranes. Multinomial logistic regression and the Wilcoxon test were applied to analyze the associations. In the cohort study, 6381 pregnant women were included. We found that VD deficiency in T3 (PTB without PROM: OR = 1.90, 95% CI: 1.02-3.55, Term PROM (TPROM): OR = 0.76, 95% CI: 0.59-0.98) and less change of 25(OH)D between T1 and T3 (PTB without PROM: OR = 2.32, 95% CI: 1.07-5.06, TPROM: OR = 0.73, 95% CI: 0.56-0.96) were associated with the increased risk of PTB without PROM, while there was a decreased risk of TPROM. Neither VD, nor the increase of VD during pregnancy was associated with the premature rupture of membranes preterm delivery (PPROM). In the case-control study, there were no associations between VD during delivery and PTB or PROM (TPROM: OR = 1.33, 95% CI: 0.52-3.44); PTB without PROM: OR = 1.66, 95% CI: 0.33-8.19; PPROM: OR = 1.19, 95% CI: 0.42-3.40). The mRNA expression of NLRP1 (NOD-like receptor thermal protein domain associated protein 1) (p = 0.0165) in PBMC in the TPROM group was higher than that in the term group, and IL-18 (p = 0.0064) was lower than that in the term group. Plasma 25(OH)D in T3 and the increase of 25(OH)D between T1 and T3 were associated with a lower risk for PTB without PROM but a higher risk for TPROM. Further studies are warranted to clarify the association between VD and PTB and PROM and its mechanism.

Serial recombination during circulation of type 1 wild-vaccine recombinant polioviruses in China.

Type 1 wild-vaccine recombinant polioviruses sharing a 367-nucleotide (nt) block of Sabin 1-derived sequence spanning the VP1 and 2A genes circulated widely in China from 1991 to 1993. We surveyed the sequence relationships among 34 wild-vaccine recombinants by comparing six genomic intervals: the conserved 5'-untranslated region (5'-UTR) (nt 186 to 639), the hypervariable portion of the 5'-UTR (nt 640 to 742), the VP4 and partial VP2 genes (nt 743 to 1176), the VP1 gene (nt 2480 to 3385), the 2A gene (nt 3386 to 3832), and the partial 3D gene (nt 6011 to 6544). The 5'-UTR, capsid (VP4-VP2 and VP1), and 2A sequence intervals had similar phylogenies. By contrast, the partial 3D sequences could be distributed into five divergent genetic classes. Most (25 of 34) of the wild-vaccine recombinant isolates showed no evidence of additional recombination beyond the initial wild-Sabin recombination event. Eight isolates from 1992 to 1993, however, appear to be derived from three independent additional recombination events, and one 1993 isolate was derived from two consecutive events. Complete genomic sequences of a representative isolate for each 3D sequence class demonstrated that these exchanges had occurred in the 2B, 2C, and 3D genes. The 3D gene sequences were not closely related to those of the Sabin strains or 53 diverse contemporary wild poliovirus isolates from China, but all were related to the 3D genes of species C enteroviruses. The appearance within approximately 2.5 years of five recombinant classes derived from a single ancestral infection illustrates the rapid emergence of new recombinants among circulating wild polioviruses.