Objective: High prevalence rates of gestational diabetes mellitus (GDM) is a public health concern worldwide. The mechanism that leads to glucose tolerance beyond normal physiological levels to pathogenic conditions remains incompletely understood, and it is speculated that the maternal microbiome may play an important role. The objective of this study is to analyze the gut microbiota composition in each trimester of weight-matched women with and without GDM and examined possible bacterial genera associations. Design: A cohort study. Setting: This study was conducted in an outpatient clinic at the Federal University of São Paulo. Population: 56 women with GDM and 59 without during their first/second or third trimester of gestation. Methods: They were submitted to a standardized questionnaire, dietary recalls, clinical examination, biological samples collection and molecular profile of the fecal microbiota. Results: There was no difference in the alpha diversity and in the overall microbiota structure. A higher abundance of Bacteroides in GDM group was found. A positive correlation between Christensenellaceae and Intestinobacter abundances with 1-hour post-challenge plasma glucose and a negative correlation between Enterococcus and 2-hour plasma glucose level were observed. Bifidobacterium and Peptococcus abundances were increased in the third gestational trimester for both groups. Conclusion: The gut microbiota composition wasn’t dependent on the presence of GDM during the whole gestation. However, some genera abundances showed associations with glucose metabolism. Our findings may motivate deepening the knowledge about physiological and pathophysiological changes in the microbiota throughout pregnancy, which could have further implications for diseases prevention.

Objective This study aims to determine the performance of cervical pessary in singleton pregnancies with a short cervix based on the learning curve. Design, Settings, Population, and Methods Between 2011 and 2018, 128 singleton gestation between 18th to 24th weeks with a short cervix (<25mm) were referred to our quasi-randomized trial. All cases were treated with progesterone, and, when available, cervical pessary was also offered. Three groups were created for statistical analysis: Group 1 (n=33), treated with progesterone-only; Group 2 and Group 3, treated with cervical pessary plus progesterone. Group 2, included the first cases (n=30), defined by the learning curve and cumulative sum analysis (LC-CUSUM), while Group 3, included the subsequent (n=65). Our outcome was delivery before 34 weeks. Main outcome measures and Results LC-CUSUM demonstrated that 30 patients achieved learning. The preterm birth rate before 34 weeks was 27.3% in Group 1, 20% in Group 2, and 4.6% in Group 3. There was no significant difference in the Group 1/Group 2 comparison (OR 1.10, P=0.945); the Group 1/Group 3 comparison, the difference was significant (OR 0.08, P=0.003). Conclusion LC-CUSUM determined 30 pessaries to achieve the best pessary performance. Cervical pessary plus progesterone can reduce the preterm birth before 34 weeks in patients with a short cervix. Funding This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001 Keywords Preterm birth; learning curve; cervical pessary; vaginal progesterone; singleton pregnancy; short cervix; transvaginal ultrasound.

Objective Does the combined analysis of compounds in vaginal secretions plus vaginal microbiota composition improve the ability to predict risk for spontaneous preterm birth (SPTB) in women with a short cervix. Design Prospective observational study Setting Three hospitals in Brazil Samples Vaginal secretions from 568 women at 21-24 weeks gestation with cervical length measurement. Method Vaginal microbiome composition was determined by analysis of the V1-V3 region of the bacterial 16S ribosomal RNA gene. D- lactic acid and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in vaginal secretions were measured by ELISA. Main outcome measures SPTB in relation to cervical length and dominant vaginal bacteria. Results When Lactobacillus crispatus was the dominant bacterium the concentration of TIMP-1 was lower, and D-lactic acid was higher, than when either L. iners or Gardnerella vaginalis predominated (p < 0.001). By ROC analysis, a D-lactic acid level < 0.7 mM, and a TIMP-1 level > 1.5 ng/ml best predicted the absence of L. crispatus dominance. Vaginal levels of TIMP-1 were highest (p = 0.024) and D-lactic acid levels were lowest (p=0.032) in women with the shortest cervical length. The absence of L. crispatus dominance increased the sensitivity for predicting a SPTB from 22.4% to 81.8% or 78.3% in women with a cervical length <25mm or <30mm, respectively. Conclusions Low vaginal D-lactic acid and high TIMP-1 indicates the loss of L. crispatus dominance and increased risk for SPTB in women with a short cervix.