Evidence of lower oxygen reserves during labour in the growth restricted human foetus: a retrospective study.

BACKGROUND: The aim of the present study is to test the hypothesis that Growth Restricted foetuses (FGR) have the tendency to develop more pathological cardiotocograpic tracings during labour than do appropriate for gestational age foetuses and that there is a shorter time lapse from the beginning of labour and the advent of a pathological cardiotocograpic tracing. METHODS: The study was carried out at the Maternal-Foetal Medicine Unit of the Sant'Anna University Hospital, Turin, Italy. A total of 930 foetuses born at term between January and December 2012 were analysed: 355 small for gestational age (SGA) comprising both constitutional small for gestational age and growth restricted foetuses (cases group) and 575 Appropriate for Gestational Age (AGA) foetuses (control group). Tracings were evaluated independently by two obstetric consultants, according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. The main outcomes considered were the incidence of pathological cardiotocograpic tracings and the time interval between the beginning of labour and the advent of pathological cardiotocograpic tracing. The Student's t-test, chi-square test and ANOVA were used for comparisons between cases and controls and amongst groups. Significance was set at <0.05. Univariate and multivariate odds-ratios were calculated. RESULTS: Foetuses with birthweight <3rd centile (growth restricted foetuses) more frequently presented pathological cardiotocograpic tracings in labour than did controls (43.8% vs. 21.6%; p < 0.001). Pathological cardiotocograpic tracing developed faster in the foetuses with birthweight <3rd centile group (53', 0'-277') than it did in the control group (170.5', 0'-550'; p < 0.05). A higher induction rate was observed in the cases (29.6%) than in the control group (17%), with statistical significance p < 0.001. To correct for this possible confounding factor a multivariate logistic regression analysis was performed. It confirmed a statistically significant increased risk of pathological cardiotocographic tracings in the FGR group (OR 1.63; CI 1.30-2.05). CONCLUSION: The results confirm the hypothesis that Growth Restricted foetuses (FGR) have fewer oxygen reserves to deal with labour. Our results underscore the importance of the prenatal detection of these foetuses and of their continuous cardiotocographic monitoring during labour.

Diet-Gut Microbiota Interactions and Gestational Diabetes Mellitus (GDM).

Medical nutritional therapy is the first-line approach in managing gestational diabetes mellitus (GDM). Diet is also a powerful modulator of the gut microbiota, whose impact on insulin resistance and the inflammatory response in the host are well known. Changes in the gut microbiota composition have been described in pregnancies either before the onset of GDM or after its diagnosis. The possible modulation of the gut microbiota by dietary interventions in pregnancy is a topic of emerging interest, in consideration of the potential effects on maternal and consequently neonatal health. To date, very few data from observational studies are available about the associations between diet and the gut microbiota in pregnancy complicated by GDM. In this review, we analyzed the available data and discussed the current knowledge about diet manipulation in order to shape the gut microbiota in pregnancy.

The microbiota composition of the offspring of patients with gestational diabetes mellitus (GDM).

The microbiota composition of the offspring of women with gestational diabetes mellitus (GDM), a common pregnancy complication, is still little known. We investigated whether the GDM offspring gut microbiota composition is associated with the maternal nutritional habits, metabolic variables or pregnancy outcomes. Furthermore, we compared the GDM offspring microbiota to the microbiota of normoglycemic-mother offspring. Fecal samples of 29 GDM infants were collected during the first week of life and assessed by 16S amplicon-based sequencing. The offspring's microbiota showed significantly lower α-diversity than the corresponding mothers. Earlier maternal nutritional habits were more strongly associated with the offspring microbiota (maternal oligosaccharide positively with infant Ruminococcus, maternal saturated fat intake inversely with infant Rikenellaceae and Ruminococcus) than last-trimester maternal habits. Principal coordinate analysis showed a separation of the infant microbiota according to the type of feeding (breastfeeding vs formula-feeding), displaying in breast-fed infants a higher abundance of Bifidobacterium. A few Bacteroides and Blautia oligotypes were shared by the GDM mothers and their offspring, suggesting a maternal microbial imprinting. Finally, GDM infants showed higher relative abundance of pro-inflammatory taxa than infants from healthy women. In conclusion, many maternal conditions impact on the microbiota composition of GDM offspring whose microbiota showed increased abundance of pro-inflammatory taxa.

Changes in the gut microbiota composition during pregnancy in patients with gestational diabetes mellitus (GDM).

Gestational diabetes mellitus (GDM), a common pregnancy complication, is associated with an increased risk of maternal/perinatal outcomes. We performed a prospective observational explorative study in 41 GDM patients to evaluate their microbiota changes during pregnancy and the associations between the gut microbiota and variations in nutrient intakes, anthropometric and laboratory variables. GDM patients routinely received nutritional recommendations according to guidelines. The fecal microbiota (by 16S amplicon-based sequencing), was assessed at enrolment (24-28 weeks) and at 38 weeks of gestational age. At the study end, the microbiota α-diversity significantly increased (P < 0.001), with increase of Firmicutes and reduction of Bacteroidetes and Actinobacteria. Patients who were adherent to the dietary recommendations showed a better metabolic and inflammatory pattern at the study-end and a significant decrease in Bacteroides. In multiple regression models, Faecalibacterium was significantly associated with fasting glucose; Collinsella (directly) and Blautia (inversely) with insulin, and with Homeostasis-Model Assessment Insulin-Resistance, while Sutterella with C-reactive protein levels. Consistent with this latter association, the predicted metagenomes showed a correlation between those taxa and inferred KEGG genes associated with lipopolysaccharide biosynthesis. A higher bacterial richness and strong correlations between pro-inflammatory taxa and metabolic/inflammatory variables were detected in GDM patients across pregnancy. Collectively these findings suggest that the development of strategies to modulate the gut microbiota might be a potentially useful tool to impact on maternal metabolic health.

Severe diabetic nephropathy in type 1 diabetes and pregnancy--a case series.

BACKGROUND: Diabetes and nephropathy are important challenges during pregnancy, increasingly encountered because of the advances in maternal-fetal care. AIM: To evaluate the maternal and fetal outcomes recorded in "severe" diabetic nephropathy in type 1 diabetic patients referred to nephrological healtcare. METHODS: The study was performed in an outpatient unit dedicated to kidney diseases in pregnancy (with joint nephrological and obstetric follow-up and strict cooperation with the diabetes unit). 383 pregnancies were referred to the outpatient unit in 2000-2012, 14 of which were complicated by type 1 diabetes. The report includes 12 deliveries, including 2 pregnancies in 1 patient; one twin pregnancy; 2 spontaneous abortions were not included. All cases had long-standing type 1 diabetes (median of 21 (15-31) years), relatively high median age (35 (29-40) years) and end-organ damage (all patients presented laser-treated retinopathy and half of them clinical neuropathy). Median glomerular filtration rate (GFR) at referral was 67 ml/min (48-122.6), proteinuria was 1.6 g/day (0.1-6.3 g/day). RESULTS: Proteinuria steeply increased in 11/12 patients, reaching the nephrotic range in nine (6 above 5 g/day). One patient increased by 2 chronic kidney disease (CKD) stages. Support therapy included blood pressure and diabetes control, bed rest, and moderate protein restriction. All children were preterm (7 early preterm); early spontaneous labor occurred in 4/12 patients. All singletons were appropriate for gestational age and developed normally after birth. The male twin child died 6 days after birth (after surgery for great vessel transposition). CONCLUSIONS: Diabetic patients with severe diabetic nephropathy are still present a considerable challenge. Therefore, further investigations are required, particularly on proteinuria management and the occurrence of spontaneous labor.

Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: a multicenter randomized phase III trial.

BACKGROUND: The most appropriate timing of chemotherapy and hormone therapy administration is a critical issue in early breast cancer patients. The purpose of our study was to compare the efficacy of concurrent vs sequential administration of adjuvant chemotherapy and tamoxifen. METHODS: Women with node-positive primary breast cancer were randomly assigned to receive tamoxifen (20 mg/d for 5 years) during (concurrent arm) or after (sequential arm) adjuvant chemotherapy. Chemotherapy consisted of alternating regimens of cyclophosphamide, epidoxorubicin, and 5-fluorouracil and cyclophosphamide, methotrexate, and 5-fluorouracil every 21 days for a total of 12 cycles. The primary endpoint was overall survival (OS), and secondary endpoints were toxic effects and disease-free survival (DFS). No provision for interim analyses was made in the original study protocol. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models, adjusted for age, menopausal status, tumor stage, and lymph node and hormone receptor status, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: From 1985 to 1992, 431 patients were randomly assigned and studied according to the intention-to-treat principle. After a maximum of 15.4 years of follow-up (median 12.3 years), the estimated actuarial 10-year OS was equivalent for the two study arms (concurrent arm: 111 patients, 66%, 95% CI = 59% to 72%; sequential arm: 114 patients, 65%, 95% CI = 59% to 72%, P = .86). No differences in DFS and toxic effects were evident. Four interim analyses were performed, but no alpha error adjustment was necessary because of the largely negative results of this final analysis (sequential vs concurrent arm: HR of death = 1.06, 95% CI = 0.78 to 1.44, P = .76; HR of relapse = 1.16, 95% CI = 0.88 to 1.52, P = .36). CONCLUSIONS: No statistically significant differences in OS, DFS, and toxic effects between concurrent and sequential adjuvant chemo- and hormone therapies were observed. Our study does not support the superiority of one schedule of chemo- and hormone-therapy administration over the other. However, because of the limited statistical power of the study, these results must be considered with caution.