Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy.

BACKGROUND: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP. METHODS: We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites. RESULTS: An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP. CONCLUSIONS: Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.

The association between serum folate and gestational diabetes mellitus: a large retrospective cohort study in Chinese population.

OBJECTIVE: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. DESIGN: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage-response relationship between serum folate and the risk of GDM. SETTING: A sigle, urban hospital in Shanghai, China. PARTICIPANTS: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. RESULTS: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs). CONCLUSIONS: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

Association between thyroid function and risk of gestational diabetes mellitus in assisted pregnancies: A retrospective cohort study.

AIMS: To explore the association between thyroid function and gestational diabetes mellitus (GDM) risk in assisted pregnancies. METHODS: We screened 57,386 pregnant women treated from February 2013 to October 2017, and 2211 patients were retrospectively enrolled, and their data were analyzed based on quintile groups constituted based on serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels. Odds ratios (ORs) of GDM were analyzed by multivariate logistic regression, adjusted for maternal age and pre-pregnancy body mass index (BMI). RESULTS: The prevalence rate of GDM was 20.1%. Lower FT4 levels were associated with an increased risk of GDM (ORQ2 = 1.512, 95% confidence interval [CI] 1.073-2.132, p = 0.018; ORQ1 = 1.620, 95% CI 1.161-2.261, p = 0.005), but this association disappeared after adjustments. TPOAb+ titer was associated with an increased risk of GDM (aOR = 1.472, 95% CI 1.068-2.028, p = 0.018). Higher TSH (aORQ5 = 2.882, 95% CI 1.919-6.975, p = 0.019) or lower FT4 (aORQ1 = 3.156, 95% CI 1.088-9.115, p = 0.034) levels were associated with an increased risk of GDM in assisted pregnancies for TPOAb+ patients. CONCLUSION: TPOAb+ is an independent risk factor for GDM in patients with assisted pregnancies. Higher TSH or lower FT4 levels, with TPOAb+ detection, are risk factors for GDM in assisted pregnancies.

Extracellular matrix remodeling effects of serum amyloid A1 in the human amnion: Implications for fetal membrane rupture.

PROBLEM: Rupture of fetal membranes is a crucial event at parturition, which is preceded by extensive extracellular matrix (ECM) remodeling. Our recent studies have demonstrated that the human fetal membranes are capable of de novo synthesis of serum amyloid A1 (SAA1), an acute phase protein, and the abundance of SAA1 in the amnion was increased at parturition. However, the exact role of SAA1 in human parturition remains to be established. METHOD OF STUDY: The effects of SAA1 on the abundance of collagenases and lysyl oxidase, the enzyme that cross-links collagens, were investigated in culture primary human amnion fibroblasts and tissue explants with an aim to examine the involvement of SAA1 in the ECM remodeling in the amnion. RESULTS: Serum amyloid A1 (SAA1) time- and dose-dependently increased the abundance of collagenases MMP-1, MMP-8, and MMP-13, while decreased the abundance of lysyl oxidase-like 1 (LOXL1). These effects of SAA1 were attenuated by siRNA-mediated knockdown of the Toll-like receptor (TLR) 4 and its antagonist CLI-095, but not by siRNA-mediated knockdown of TLR2. Furthermore, the inhibitors for NF-κB (JSH-23) and mitogen-activated protein kinases (MAPKs) p38 (SB203580) and JNK (SP600125) could also attenuate the effects of SAA1, while the inhibitor for MAPK ERK1/2 (PD 98059) could block the effects of SAA1 only on MMP-1, MMP-8, and LOXL1 but not on MMP-13. CONCLUSION: These data highlight a possible role for SAA1 in ECM remodeling preceding membrane rupture by regulating the expression of collagenases MMP-1, MMP-8, MMP-13, and LOXL1 through TLR4-mediated activation of the NF-κB and MAPK pathways in amnion fibroblasts.

[Impact of uterine fibroid embolization with danazol alginate microsphere on ovarian function and subsequent pregnancy].

OBJECTIVE: To investigate the impact of danazol alginate microspheres used for uterine arterial embolization (UAE) on ovarian function and subsequent pregnancy using rabbit as a model. METHODS: A total of 32 female rabbits were divided into 3 groups: a control group, danazol alginate microspheres (DKMG) group and alginate microspheres (KMG) group. Basal serum estradiol (E(2)), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) levels before UAE and 1 - 3 months after UAE were compared for all rabbits. In breeding field all rabbits mated after UAE. Estrus, and pregnancy rate were observed by veterinary. RESULTS: There were no significant changes from baseline FSH, LH, E(2), T levels measured at 1, 2 and 3 months after UAE (P > 0.05). The total pregnancy rate of DKMG or KMG group was 0 within 2 - 4 months after UAE. Compared to the control group (4/8), the difference was statistically significant (P < 0.05); the total pregnancy rate of DKMG, KMG and control groups within 5 - 7 months after UAE, respectively 17% (2/12), 25% (3/12) and 5/8 (P > 0.05); the total pregnancy rate was 42% (5/12), 50% (6/12) and 6/8 respectively within 8 - 10 months after UAE, there were also no significant differences between the three groups (P > 0.05). CONCLUSIONS: There is no obvious effect of danazol alginate microspheres used for uterine arterial embolization on ovarian function in rabbits. After UAE some animals are able to achieve pregnancies, while harmful effects are observed on short term pregnant rate.

Maternal TSH level and TPOAb status in early pregnancy and their relationship to the risk of gestational diabetes mellitus.

Subclinical hypothyroidism is common in pregnant women and often related to adverse pregnancy outcomes, but its relationship with gestational diabetes remains controversial. In particular, the impact of thyroperoxidase antibodies status on the relationship between subclinical hypothyroidism and gestational diabetes is not clear. We investigated the association between combined thyroid stimulating hormone (TSH) level and thyroperoxidase antibodies status in early pregnancy (<20 weeks of gestation) and gestational diabetes mellitus. A total of 7084 pregnant women met the inclusion criteria, which included thyroperoxidase antibodies-positive subclinical hypothyroidism [TSH(H)TPOAb(+)] (n = 78), thyroperoxidase antibodies-negative subclinical hypothyroidism [TSH(H)TPOAb(-)] (n = 281), thyroperoxidase antibodies-positive euthyroidism [TSH(N)TPOAb(+)] (n = 648), and thyroperoxidase antibodies-negative euthyroidism [TSH(N)TPOAb(-)] (n = 6077). Of the 7084 cases included in our study, 1141 cases were diagnosed with gestational diabetes mellitus at 24-28 weeks of pregnancy. The prevalence of gestational diabetes mellitus in TSH(N)TPOAb(-), TSH(H)TPOAb(-), TSH(N)TPOAb(+), and TSH(H)TPOAb(+) was 14.65, 19.57, 24.85, and 46.15 %, respectively. Compared with TSH(N)TPOAb(-) women, the risk of gestational diabetes mellitus was increased in all other groups of women in early pregnancy. After dividing early pregnancy into first and second trimesters, we found that TSH(H)TPOAb(-) women in the first trimester do not show this increase. Our study suggests that subclinical hypothyroidism and thyroperoxidase antibodies-positive euthyroidism in early pregnancy are associated with an increased risk of gestational diabetes mellitus.

Use of early transverse annular compression sutures for complete placenta previa during cesarean delivery.

OBJECTIVE: To compare the difference in maternal outcomes between early and late use of transverse annular compression sutures (TACS) during cesarean delivery among women with complete placenta previa (CPP). METHODS: A retrospective study of 36 women with CPP was conducted. Percentiles of blood loss before TACS were calculated. The transfusion rate, sensitivity, specificity, Youden index, positive predictive value, and negative predictive value were also estimated. Patients were assigned to either the early TACS group or the late TACS group based on the highest Youden index. Maternal outcomes of the 2 groups were compared. RESULTS: The Youden index for transfusion rate was highest when blood loss before TACS reached 500 mL. Blood loss before intervention in the late TACS group was significantly higher than in the early TACS group (735.0 ± 123.7 mL versus 396.9 ± 76.3 mL; P<0.001). More women in the late TACS group than in the early TACS group required blood transfusion (60.0% versus 12.5%; P=0.004) and the volume of blood transfused was significantly lower in the early TACS group than in the late TACS group (137.5 ± 377.5 mL versus 806.7 ± 619.3 mL; P=0.001). CONCLUSION: Early implementation of TACS could lead to improved maternal outcomes.