"Residential greenness, gestational diabetes mellitus (GDM) and microbiome diversity during pregnancy".

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with reduced gut microbiota richness that was also reported to differ significantly between those living in rural compared to urban environments. Therefore, our aim was to examine the associations between greenness and maternal blood glucose levels and GDM, with microbiome diversity as a possible mediator in these associations. METHODS: Pregnant women were recruited between January 2016 and October 2017. Residential greenness was evaluated as mean Normalized Difference Vegetation Index (NDVI) within 100, 300 and 500 m buffers surrounding each maternal residential address. Maternal glucose levels were measured at 24-28 weeks of gestation and GDM was diagnosed. We estimated the associations between greenness and glucose levels and GDM using generalized linear models, adjusting for socioeconomic status and season at last menstrual period. Using causal mediation analysis, the mediation effects of four different indices of microbiome alpha diversity in first trimester stool and saliva samples were assessed. RESULTS: Of 269 pregnant women, 27 participants (10.04%) were diagnosed with GDM. Although not statistically significant, adjusted exposure to medium tertile levels of mean NDVI at 300 m buffer had lower odds of GDM (OR = 0.45, 95% CI: 0.16, 1.26, p = 0.13) and decreased change in mean glucose levels (ß = -6.28, 95% CI: 14.91, 2.24, p = 0.15) compared to the lowest tertile levels of mean NDVI. Mixed results were observed at 100 and 500 m buffers, and when comparing highest tertile levels to lowest. No mediation effect of first trimester microbiome on the association between residential greenness and GDM was observed, and a small, possibly incidental, mediation effect on glucose levels was observed. CONCLUSION: Our study suggests possible associations between residential greenness and glucose intolerance and risk of GDM, though without sufficient evidence. Microbiome in the first trimester, while involved in GDM etiology, is not a mediator in these associations. Future studies in larger populations should further examine these associations.

Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

Fetal Renal to Abdominal Ratio: A Constant Measurement Throughout Gestation.

BACKGROUND: Sonographic assessment of the fetal kidneys is an integral part of the prenatal anatomical survey. OBJECTIVES: To evaluate the fetal renal to abdominal (RTA) ratio throughout pregnancy and to investigate whether this ratio can be a potential diagnostic landmark for congenital anomalies of the kidney and urinary tract (CAKUT). METHODS: Measurements of the anterior-posterior diameters of the fetal kidney and fetal abdomen (APAD) were obtained prospectively. The RTA was calculated as the ratio between them in in two groups: normal population vs. CAKUT cases. RTA in CAKUT cases was compared to RTA in a normal population. RESULTS: The study group was comprised of 210 women. The mean gestational age for the fetuses was 31 ± 5.6 weeks (range 14-40 weeks). Fetal RTA ratio was found to be 0.28 ± 0.03 throughout pregnancy from early second trimester to term, with high reproducibility of measurements. During the study period the RTA was evaluated in nine cases referred for suspected CAKUT. All cases demonstrated a different ratio according to the renal anomaly. High ratio was observed in one case of overgrowth syndrome (Beckwith Wiedenmann syndrome; 0.47), three cases of infantile polycystic kidney (0.45-0.47), and three cases of a solitary kidney (0.31-0.35), while cases of dysplastic kidneys revealed a low ratio (0.14-0.18). CONCLUSIONS: Prenatal RTA ratio is constant throughout gestation. An abnormal ratio should lead to meticulous renal investigation to rule out kidney disease.

Association and risk factors between induction of labor and cesarean section.

OBJECTIVE: To determine risk factors and to quantify the risk of cesarean section (CS) associated with labor induction. METHOD: A prospective controlled study of women admitted for labor induction with PGE2 in a single tertiary medical center. Outcome was compared with women who presented with spontaneous onset of delivery. RESULTS: The induction group were characterized by a higher body mass index (BMI), lower Bishop score and a higher cervical length at presentation compared with controls. Labor induction with PGE2 was associated with increased risk of CS (14.8% versus 4.5%, p = 0.02). This association persists after adjustment for potential confounders including Bishop score at presentation (OR = 2.9, 95% CI 1.03-11.8). The risk of CS was especially high for nulliparous (24.4% versus 5.1%, p = 0.02), overweight (21.2% versus 3.7%, p = 0.047), induction at <40 weeks of gestation (22.2% versus 2.2%, p = 0.004), in Bishop score <4 (18.2% versus 4.5%, p = 0.03), cervical length >25 mm (19.2% versus 4.5%, p = 0.005), or intact membranes (25.0% versus 4.5%, p = 0.02) at presentation. CONCLUSIONS: Labor induction with PGE2 is associated with increased risk of CS. These data should be taken into consideration when deciding on labor induction, especially in the absence of clear medical indication.

Labor induction with prostaglandin E2: characteristics of response and prediction of failure.

OBJECTIVE: To characterize the response to labor induction with prostaglandin E2 (PGE2) and to identify risk factors for induction failure. METHODS: A prospective controlled study of women admitted for labor induction with PGE2. Maternal characteristics, Bishop score and sonographic cervical length were documented at admission. The change in cervical characteristics and the emergence of uterine contractions following each application of PGE2 were analyzed. RESULTS: Of the 88 women who were included in the study, 19 (21.6%) failed to response to PGE2. The following factors were independently associated with induction failure: nulliparity (odds ratio [OR] = 5.9, 95% confidence interval (CI): 1.2-30.2), pre-pregnancy body mass index >25 kg/m2 (OR = 5.4, 95% CI: 1.1-26.5), Bishop score <4 (OR = 2.3, 95% CI: 1.05-14.4), cervical length <25 mm (OR = 0.2, 95% CI: 0.1-0.8) and the development of uterine contractions in response to the first application of PGE2 (OR = 0.4, 95% CI: 0.1-0.93). Overall, most women required only one (60.9%) or two (85.5%) applications of PGE2 to achieve successful induction. The number of applications of PGE2 required to achieve successful induction was related to parity and cervical status at presentation. CONCLUSIONS: Overall, most women who eventually respond to PGE2 do so following the first two applications of PGE2, and the contribution of subsequent applications is relatively small and related to cervical status at admission.