High-performance lung-targeted bio-responsive platform for severe colistin-resistant bacterial pneumonia therapy.

Polymyxins are the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. However, this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resistance gene-1 (mcr-1). Given the high concentration of matrix metalloproteinase 3 (MMP-3) in bacterial pneumonia, limited plasma accumulation of colistin (CST) in the lung, and potential toxicity of ionic silver (Ag+), we designed a feasible clinical transformation platform, an MMP-3 high-performance lung-targeted bio-responsive delivery system, which we named "CST&Ag@CNMS". This system exhibited excellent lung-targeting ability (>80% in lungs), MMP-3 bio-responsive release property (95% release on demand), and synergistic bactericidal activity in vitro (2-4-fold minimum inhibitory concentration reduction). In the mcr-1+ CST-resistant murine pneumonia model, treatment with CST&Ag@CNMS improved survival rates (70% vs. 20%), reduced bacteria burden (2-3 log colony-forming unit [CFU]/g tissue), and considerably mitigated inflammatory response. In this study, CST&Ag@CNMS performed better than the combination of free CST and AgNO3. We also demonstrated the superior biosafety and biodegradability of CST&Ag@CNMS both in vitro and in vivo. These findings indicate the clinical translational potential of CST&Ag@CNMS for the treatment of lung infections caused by CST-resistant bacteria carrying mcr-1.

The role of dietary fiber on preventing gestational diabetes mellitus in an at-risk group of high triglyceride-glucose index women: a randomized controlled trial.

BACKGROUND: Pregnant women with a high triglyceride-glucose (TyG) index during early pregnancy may increase the risk of gestational diabetes mellitus (GDM), and dietary fiber could play an important role in glucose and lipid metabolism. However, no trials have tested the effects of dietary fiber on preventing GDM in women with a high TyG index. This study aims to investigate whether GDM can be prevented by dietary fiber supplementation in women with a TyG index ≥8.5 during early pregnancy (<20 weeks). METHODS: A randomized clinical trial was performed among 295 women with a TyG index ≥8.5 before 20 weeks of gestation, divided into a fiber group (24 g dietary fiber powder/day) or a control group (usual care). The intervention was conducted from 20 to 24+6 gestational weeks, and both groups received guidance on exercise and diet. The primary outcomes were the incidence of GDM diagnosed by a 75 g oral glucose tolerance test at 25-28 gestational weeks, and levels of maternal blood glucose, lipids. Secondary outcomes include gestational hypertension, postpartum hemorrhage, preterm birth, and other maternal and neonatal complications. RESULTS: GDM occurred at 11.2% (10 of 89) in the fiber group, which was significantly lower than 23.7 (44 of 186) in the control group (P = 0.015). The mean gestational weeks increased dramatically in the fiber group compared with the control group (39.07 ± 1.08 vs. 38.58 ± 1.44 weeks, P = 0.006). The incidence of preterm birth was 2.3% (2 of 86) of women randomized to the fiber group compared with 9.4% (17 of 181) in the control group (P = 0.032). The concentrations of 2 h postprandial blood glucose showed statistically higher in the control group compared with the intervention group (6.69 ± 1.65 vs. 6.45 ± 1.25 mmol/L, P = 0.026). There were no other significant differences between groups in lipid profile values, or other secondary outcomes. CONCLUSION: An intervention with dietary fiber supplementation during pregnancy may prevent GDM and preterm birth in women with a TyG index ≥8.5 before 20 weeks of gestation.

Evaluating the accuracy of sonographic fetal weight estimations using the Hadlock IV formula in a Chinese population.

Background: Despite being the most generalized formula in China, the Hadlock IV formula has never been examined to determine if it is suitable for Chinese newborns, nor have the factors that might affect its performance been investigated. However, previous studies have reported varying results about other formulas in other nationalities. This study sought to evaluate the performance of the Hadlock IV formula in estimating fetal weight (FW) in pregnant Chinese women and use ultrasound to identify the factors affecting the accuracy of estimations of newborn weight; through these means, we aimed to create a reference for predicting neonatal weight for obstetricians. Methods: A retrospective observational study comprising data from 976 cases of live-birth singleton pregnancies at the Shanghai General Hospital was conducted. The participants' clinical data were examined and subjected to a logistic regression analysis to identify the multitude of possible factors affecting the estimation of FW. The proportions and correlations between the accurate and inaccurate estimation groups were compared to determine the different prognosis of these 2 groups. The correlations between the accuracy of the sonographic-based fetal weight estimation (SFWE) and newborns with different weight ranges were also analyzed. Results: The overall accuracy rate of the SFWE predicted by the Hadlock IV formula was 79.61%, while that of the inaccurate estimation group was only 20.39%. The incidence of spontaneous vaginal delivery (VD) was lower in the inaccurate estimation group than in the accurate estimation group (40.7% vs. 48.13%; P=0.041). In the inaccurate estimation group, 11.56% (23/199) of the participants underwent a secondary cesarean section (sCS), compared to only 6.44% (50/777) in the accurate estimation group. The low birth weight (LBW) rates and macrosomia rates were lower in the accurate estimation group than in the inaccurate estimation group, with odds ratios (ORs) of 0.483 and 0.459, respectively (P<0.05). The results indicated that the SFWE was more accurate for newborns weighing 2,500-4,000 g than those weight out of this range. In relation to macrosomia, the SFWE was likely to be underestimated, but it was usually overestimated in the LBW group. Conclusions: The overall performance of the Hadlock IV formula in predicting the birth weight of Chinese newborns remains suboptimal. Extra caution should be exercised in cases of suspected large-for-gestational age (LGA) infants, small-for-gestational age (SGA) infants, infants with macrosomia, or LBW fetuses in the Chinese population.

Effects of Dietary Fiber on the Risk of Gestational Diabetes Mellitus in Advanced Maternal Age Women: Study Protocol for a Randomized Controlled Trial.

SCOPE: To investigate whether dietary fiber supplementation may reduce the risk of gestational diabetes mellitus (GDM) in advanced maternal age Chinese women (≥35 years). Secondary outcomes include glucose metabolism, diet change, weight gain, and maternal and neonatal outcomes. METHODS AND RESULTS: In a randomized controlled trial, a dietary fiber group (19.56 g day-1 ) or control group (standard prenatal care) was conducted from 20 to 24+6 gestational weeks in advanced maternal age women. Dietary intakes were assessed using a validated 39-item Food Frequency Questionnaire (FFQ). GDM was diagnosed by a 75 g oral glucose tolerance test (OGTT) at 25-28 weeks. After intervention, the incidence of GDM was not significantly different between groups (21.6% vs 12.9%, p = 0.165). The mean increased in carbohydrate intake in the dietary fiber group is significantly lower than in the control group (-0.94 ± 92.12 g vs 32.27 ± 91.81 g, p = 0.032). In addition, the glucose tolerance, weight gain between 20 and 25 weeks, and preterm birth in the intervention group have improved compared to the control group. CONCLUSION: Supplementation with dietary fiber during pregnancy among advanced maternal age Chinese women do not lower the incidence of GDM, but improve glucose metabolism, gestational weight gain, and preterm birth.

Corrigendum: Insulin treatment of hypertriglyceridemia during pregnancy.

[This corrects the article DOI: 10.3389/fphar.2021.785756.].

The effect of dietary fiber supplement on prevention of gestational diabetes mellitus in women with pre-pregnancy overweight/obesity: A randomized controlled trial.

Objective: To investigate the effect of dietary fiber intake during pregnancy on the prevention of gestational diabetes mellitus (GDM) in women who are overweight/obese prior to pregnancy. Methods: This randomized controlled trial was conducted in Shanghai General Hospital from June 2021 to March 2022. A total of 98 women who reported BMI≥24 kg/m2 prior to pregnancy were recruited before their 20th gestational week, and randomly (simple random allocation) assigned to the fiber supplement group (12 g of dietary fiber power twice daily) and the control group (standard prenatal care) from 20 to 24+6 gestational weeks. Both groups received nutrition education and dietary advice during the study. GDM diagnosis was performed by an oral glucose tolerance test (OGTT) at 25-28 weeks' gestation. Data are presented as means with SD, as medians with IQR, or as counts with percentages as appropriate. Comparisons were conducted using a t-test, Mann-Whitney U test, and χ2 test, respectively. Results: The incidence of GDM was significantly reduced in the fiber supplement group compared with the control group: 8.3 vs. 24.0% (χ2 = 4.40, p = 0.036). At OGTT, the mean fasting plasma glucose in the fiber supplement group was significantly lower than before the intervention (4.57 ± 0.38 mmol/L vs. 4.41 ± 0.29 mmol/L, p < 0.01) but not in the control group (4.48 ± 0.42 mmol/L vs. 4.37 ± 0.58 mmol/L, p = 0.150). Compared with the control group, the TG and TG/HDL-C ratio levels in the intervention group were significantly higher than those in the control group (2.19 ± 0.54 mmol/L vs. 2.70 ± 0.82 mmol/L and 1.19 ± 0.49 vs.1.63 ± 0.63, respectively, all P＜0.05). The body weight gain was significantly lower in the fiber supplement group than the control group (1.99 ± 1.09 kg vs. 2.53 ± 1.20kg, p = 0.022). None of the women randomized to the fiber supplement group experienced preterm birth (<37 weeks gestation) compared with 12.0% in the control group (p = 0.040). Excessive weight gain (total weight gain >11.5 kg for overweight, and >9.0 kg for obesity) occurred in 46.7% of women in the fiber supplement group compared with 68.0% in the control group (p = 0.035). There were no differences in other maternal and neonatal outcomes. Conclusion: Increased dietary fiber intake in pregnant women who were overweight/obese prior to pregnancy may reduce the risk of GDM, excessive weight gain, and preterm birth, but it did not improve blood lipids.

Associations of Thyroid Function Tests with Lipid Levels and Adverse Pregnancy Outcomes During the First Trimester.

Objective: The present study aims to evaluate the relationship of thyroid function during the first trimester of pregnancy with lipid levels and pregnancy outcomes. Methods: Women who delivered babies at the Shanghai General Hospital between March 2019 and December 2019 with a known pregnancy outcome and complete data were included in the present study (n = 1779). A retrospective cohort study of all subjects with available first-trimester thyroid function testing and lipid levels data was conducted, and the relationship of thyroid function with lipid levels and pregnancy outcomes was evaluated. The data were analyzed using the SPSS software for statistical correlation. Results: The proportion of caesarean sections was higher in women with hypothyroxinemia (HIA) and hypothyroidism than in women with euthyroidism. Hypothyroidism was shown to be related with polyhydramnios, preterm labor and hypertriglyceridemia. HIA was correlated with increased rates of gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension and hypertriglyceridemia. Compared with the euthyroidism group, the hypothyroidism group had a higher apolipoprotein A1 (Apo A1) level and apolipoprotein B level; the subclinical hypothyroidism group had a higher total cholesterol (TC) level and low-density lipoprotein cholesterol level; the HIA group had higher triglyceride, high-density lipoprotein cholesterol levels and lower TC, Apo A1 levels. TC levels were positively correlated with the thyroid-stimulating hormone level and negatively correlated with free thyroxine (FT4) level, and free triiodothyronine and FT4 levels were positively correlated with GDM occurrence. Conclusion: Thyroid function in early pregnancy is associated with dyslipidemia and pregnancy outcomes; conventional screening of thyroid diseases in early pregnancy may help improve lipid levels and decrease adverse pregnancy outcomes.

Effect of exposure to antibiotics on the gut microbiome and biochemical indexes of pregnant women.

INTRODUCTION: Exposure to antibiotics (ABX) during pregnancy can have a systematic effect on both fetal and maternal health. Although previous biomonitoring studies have indicated the effects on children of extensive exposure to ABX, studies on pregnant women remain scarce. To explore the effect on pregnant women of environmental exposure to ABX through accidental ingestion and identify potential health risks, the present study investigated 122 pregnant women in East China between 2019 and 2020. RESEARCH DESIGN AND METHODS: The presence of six categories of ABX (quinolones, sulfonamides, lincosamides, tetracyclines, amide alcohol ABX, and ß-lactams) in plasma samples taken from the pregnant women was investigated using an ABX kit and a time-resolved fluorescence immunoassay. RESULTS: All six ABX were detected in the plasma, with a detection rate of 17.2%. It was discovered that the composition of intestinal flora in pregnant women exposed to ABX was different from that of pregnant women who had not been exposed to ABX. The intestinal flora of pregnant women exposed to ABX also changed at both the phylum and genus levels, and several genera almost disappeared. Furthermore, the metabolic levels of glucose and insulin and the alpha diversity of pregnant women exposed to ABX were higher than those of pregnant women not exposed to ABX. CONCLUSION: Pregnant women are potentially at higher risk of adverse microbial effects. Glucose metabolism and insulin levels were generally higher in pregnant women exposed to ABX than in unexposed women. Also, the composition and color of the gut microbiome changed.

The characteristics of intestinal flora in overweight pregnant women and the correlation with gestational diabetes mellitus.

OBJECTIVE: To investigate the characteristics of intestinal flora in overweight pregnant women and the correlation with gestational diabetes mellitus (GDM). METHODS: A total of 122 women were enrolled and divided into four groups according to their pre-pregnancy BMI and the presence of GDM: group 1 (n = 71) with a BMI <24 kg/m2, without GDM; group 2 (n = 27) with a BMI <24 kg/m2, with GDM; group 3 (n = 17) with a BMI ≥24 kg/m2, without GDM; and group 4 (n = 7) with a BMI ≥24 kg/m2 with GDM. Feces were collected on the day that the oral glucose tolerance test was conducted. The V3-V4 variable region of 16S rRNA was sequenced using the Illumina Hiseq 2500 platform, and a bioinformatics analysis was conducted. RESULTS: There were differences between the four groups in the composition of intestinal flora, and it was significantly different in group 4 than in the other three groups. Firmicutes accounted for 36.4% of the intestinal flora in this group, the lowest among the four groups, while Bacteroidetes accounted for 50.1%, the highest among the four groups, making ratio of these two bacteria approximately 3:5, while in the other three groups, this ratio was reversed. In women with a BMI <24 kg/m2, the insulin resistance index (homeostatic model assessment for insulin resistance (HOMA-IR)) in pregnant women with GDM was higher than in those without (P3 = 0.026). CONCLUSION: The composition of the intestinal flora of pregnant women who were overweight or obese before pregnancy and suffered from GDM was significantly different than women who were not overweight or did not suffer from GDM.

Corrigendum: The Role of High-Content Complex Dietary Fiber in Medical Nutrition Therapy for Gestational Diabetes Mellitus.

[This corrects the article DOI: 10.3389/fphar.2021.684898.].

Alterations of gut microbiota in gestational diabetes patients during the second trimester of pregnancy in the Shanghai Han population.

BACKGROUND: The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM. METHODS: Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA. RESULTS: Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM. CONCLUSION: Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.

Older Underweight Pregnant Women Beat Young Overweight/Obese Ones on Incidence of Gestational Diabetes.

OBJECTIVE: This study aimed to compare the incidence of gestational diabetes mellitus (GDM) in older underweight pregnant women vs young overweight/obese ones. METHODS: A multiracial retrospective-cohort study was conducted in five hospitals of Shanghai on 7,485 women who had been pregnant during 2018-2020. Incidence of GDM was equal to the proportion of GDM cases in the total number of cases observed in the same period. Comparison of GDM incidence of older underweight pregnant women and young overweight/obese ones was done with χ2 tests. ORs and 95% CIs for GDM were estimated using univariate and multivariate logistic regression across gestation age and prepregnancy BMI. RESULTS: Advanced age (OR 1.09, 95% CI 1.072-1.11; P=0) and higher BMI (OR 1.57, 95% CI 1.112-2.212; P=0.01) were found to be risk factors of GDM. The incidence of 13.33% of older underweight pregnant women (age ≥35years, BMI <18.5 kg/m2) developing GDM was lower than that of young overweight/obese ones (age ≤24 years, BMI ≥24 kg/m2). For those aged ≥35years, it is advised that BMI be kept to <18.5 kg/m2. For those aged ≤24 years, BMI control should not exceed 24 kg/m2. CONCLUSION: Older underweight (age≥35years, BMI <18.5 kg/m2) pregnant women beat young overweight/obese ones (age ≤24 years, BMI ≥24 kg/m2) on incidence of GDM. Factors influencing obesity/overweight in GDM were high maternal age, though being young is a promising protective factor for GDM and tolerance of BMI is promoted, but should be limited to certain ranges. Being older increased the chances of developing GDM, but those with lower BMI still had lower GDM incidence than younger pregnant women.

The Role of High-Content Complex Dietary Fiber in Medical Nutrition Therapy for Gestational Diabetes Mellitus.

Objectives: A controlled open clinical study was conducted to evaluate the role of Ricnoat, a high-content complex dietary fiber powder produced by Zhuhai Aimed Biotechnology Co. Ltd., in medical nutrition therapy (MNT) to treat gestational diabetes mellitus (GDM). The study aimed to investigate glycemic control, lipid control, weight control, and pregnancy outcomes (neonatal weight) in patients with GDM, as well as evaluate the clinical safety of Ricnoat. Methods: A total of 120 patients with GDM who were admitted to three hospitals in Shanghai between January 2019 and January 2020 were enrolled. Ricnoat was used for intervention for patients in the experimental group. Using a χ2 test and t-test, respectively, comparisons were conducted between the measurement data and countable data of the demographics and baseline disease characteristics of the experimental group and control group. Results: Fasting blood glucose, 2-h postprandial blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein, maternal gestational weight gain, neonatal weight, serum creatinine, glutamate transaminase, and aspartate aminotransferase were lower in the experimental group than in the control group, whereas high-density lipoprotein was higher in the experimental group than in the control group. Ricnoat intervention resulted in satiety higher than the expected 80% and more common occurrence of type 4 (smooth and soft, like salami or a snake) and type 5 (a soft mass with clear edges) stools. Conclusion: Ricnoat intervention had a significant effect on glycemic control, lipid control, weight control, and pregnancy outcomes (neonatal weight) in patients with GDM by enhancing maternal satiety and improving the stool features of pregnant women. It was also found to be safe for application during pregnancy.

Opportunities for Prevention of Gestational Diabetes Before 24 Weeks of Gestation.

BACKGROUND: Gestational diabetes (GDM), increasingly prevalent worldwide, is related to growing pregnancy complications and long-term metabolic risks for the woman and the descendants. The aim of this study is to determine the optimal BMI ranges specific for age group and optimal gestational weight gain (GWG) at 24 weeks specific for different pre-BMI (pre-pregnancy body mass index) groups to avoid or reduce the incidence of GDM. METHODS: A retrospective cohort study of 3104 pregnant women was conducted in Song Jiang district, Shanghai, China. A multivariate logistic regression analysis was performed with the purpose of determining the OR (odds ratio) of risk factors of GDM including GWG of 24 weeks, pre-BMI, advanced age, and first-degree relatives with DM. Optimal ranges of GWG or pre-BMI are defined as the interval corresponding to lowest or relative lower incidence of GDM. RESULTS: ORs of pre-BMI, maternal age, GWG at 24 weeks, and first-degree relatives with DM were 1.250, 1.096, 1.142, and 2,098 separately. It is suggested for lowering the incidence of GDM that, to the utmost extent, 12 kg, 9 kg, and 8 kg for GWG at 24 weeks should be the ideal boundary for those pregnant women whose BMI was 15-21 kg/m2, 21-23 kg/m2, and 23-25 kg/m2 respectively. Pre-BMI ≤22 kg/m2 would be recommended for an expectant mother whose age is no more than 28 years old. Similarly, women whose age was above 28 years old would be advised to control their BMI below 20 kg/m2. CONCLUSION: Optimal GWG during pregnancy varies largely by diverse pre-BMI, and likewise, optimal pre-BMI varies a lot by different age group. Public health awareness should be promoted on the importance of having healthy pre-BMI, and achieving optimal weight gain during pregnancy to avoid or reduce the incidence of GDM, especially for those with first-degree relatives with DM.

Insulin Treatment of Hypertriglyceridemia During Pregnancy.

Objective: This study aims to investigate the efficiency of insulin on the reduction of gestational lipid profiles and try to propose a real-world approach to assist clinicians. Methods: A retrospective, single-centered cohort study of 35 cases was conducted from October 2018 to July 2021 in Shanghai General Hospital. SPSS version 25.0 was performed to analyze the whole data. For continuous variables, a paired-sample t test was carried out on each variable to make a comparison between before and after treatment. Results: The average pre-pregnancy TGs and TCs of these patients were about 3.96 ± 1.42 mmol/L and 4.78 ± 1.18 mmol/L, respectively. The maximum of TG before insulin treatment was up to 64.62 and TC 20.43 mmol/L, which decreased to 17.34 and 4.92 mmol/L after intervention of the insulin drip. TG was noticed to fall by 77% and 12.71% of TG, respectively. The difference of TG and TC between pre-treatment and post-treatment were statistically significant (p < 0.01), while this difference has not been found in the other laboratory tests reports. The outcomes of newborns and mothers with management of insulin were proven to be improved. Conclusion: The use of insulin in the management of gestational hypertriglyceridemia is safe and efficient, and insulin may become a mainstream in the near future to mitigate serum TG and TC levels in the pregnancy period besides regulating the blood glucose level.