Does vaginal delivery mitigate or strengthen the intergenerational association of overweight and obesity? Findings from the Boston Birth Cohort.

BACKGROUND/OBJECTIVES: The intergenerational association of obesity may be driven by mother-to-newborn transmission of microbiota at birth. Yet cesarean delivery circumvents newborn acquisition of vaginal microbiota, and has been associated with greater childhood adiposity. Here we examined the independent and joint associations of maternal pre-pregnancy body mass index (BMI; kg m-2) and delivery mode with childhood overweight or obesity. SUBJECTS/METHODS: We prospectively followed 1441 racially and ethnically diverse mother-child dyads in the Boston Birth Cohort until age 5 years (range: 2.0-8.0 years). We used logistic regression to examine the independent and joint associations of delivery mode (cesarean and vaginal delivery) and pre-pregnancy BMI with childhood overweight or obesity (age-sex-specific BMI ⩾85th percentile). RESULTS: Of 1441 mothers, 961 delivered vaginally and 480 by cesarean. Compared with vaginally delivered children, cesarean delivered children had 1.4 (95% confidence interval (CI) 1.1-1.8) times greater odds of becoming overweight or obese in childhood, after adjustment for maternal age at delivery, race/ethnicity, education, air pollution exposure, pre-pregnancy BMI, pregnancy weight gain and birth weight. Compared with children born vaginally to normal weight mothers, after multivariable adjustment, odds of childhood overweight or obesity were highest in children born by cesarean delivery to obese mothers (odds ratio (OR): 2.8; 95% CI: 1.9-4.1), followed by children born by cesarean delivery to overweight mothers (OR: 2.2; 95% CI: 1.5-3.2), then children born vaginally to obese mothers (OR: 1.8; 95% CI: 1.3-2.6) and finally children born vaginally to overweight mothers (OR: 1.7; 95% CI: 1.2-2.3). CONCLUSIONS: In our racially and ethnically diverse cohort, cesarean delivery and pre-pregnancy overweight and obesity were associated with childhood overweight or obesity. Needed now are prospective studies that integrate measures of the maternal and infant microbiome, and other potentially explanatory covariates, to elucidate the mechanisms driving this association and to explore whether exposure to vaginal microbiota in cesarean delivered newborns may be an innovative strategy to combat the intergenerational cycle of obesity.

Creating an integrated care model for childhood obesity: a randomized pilot study utilizing telehealth in a community primary care setting.

In an integrated care model, involving primary care providers (PCPs) and obesity specialists, telehealth may be useful for overcoming barriers to treating childhood obesity. We conducted a pilot study comparing body mass index (BMI) changes between two arms (i) PCP in-person clinic visits plus obesity specialist tele-visits ( PCP visits + specialist tele-visits) and (ii) PCP in-person clinic visits only ( PCP visits only), with ongoing tele-consultation between PCPs and obesity specialists for both arms. Patients (N = 40, 10-17 years, BMI ≥ 95th percentile) were randomized to Group 1 or 2. Both groups had PCP visits every 3 months for 12 months. Using a cross-over protocol, Group 1 had PCP visits + specialist tele-visits during the first 6 months and PCP visits only during the second 6 months, and Group 2 followed the opposite sequence. Each of 12 tele-visits was conducted by a dietitian or psychologist with a patient and parent. Retention rates were 90% at 6 months and 80% at 12 months. BMI (z-score) decreased more for Group 1 (started with PCP visits + specialist tele-visits) vs. Group 2 (started with PCP visits only) at 3 months (-0.11 vs. -0.05, P = 0.049) following frequent tele-visits. At 6 months (primary outcome), BMI was lower than baseline within Group 1 (-0.11, P = 0.0006) but not Group 2 (-0.06, P = 0.08); however, decrease in BMI at 6 months did not differ between groups. After crossover, BMI remained lower than baseline for Group 1 and dropped below baseline for Group 2. An integrated care model utilizing telehealth holds promise for treating children with obesity.

Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease.

BACKGROUND: Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis. AIM: To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD. METHODS: Children with a history of recurrent CDI (≥3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT at 2-10 weeks, 10-20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed. RESULTS: Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10-20 weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased. Six months post-FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months in IBD-negative patients more closely approximated donor composition compared to IBD-positive patients. CONCLUSIONS: FMT gives sustained C. difficile eradication in children with and without IBD. FMT-restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome diversity.

The prevalence of Clostridium difficile infection in pediatric and adult patients with inflammatory bowel disease.

OBJECTIVES: Adults with inflammatory bowel disease (IBD) have a high prevalence of Clostridium difficile infection (CDI). CDI in children with IBD may differ from adults. We aim to compare the prevalence of CDI in hospitalized pediatric and adult IBD patients and patients without IBD. METHODS: The rates of CDI per 1,000 IBD and non-IBD hospitalizations between 1993 and 2012 were examined using the Maryland Health Services Cost Review Commission database. Age, sex and calendar year adjusted incidence rate ratios comparing CDI in pediatrics and adults by type of IBD and with patients without IBD were calculated. p values for trend identifying changes in rates over time were calculated. RESULTS: Among children, the rate of CDI was over 12 times greater in IBD than non-IBD hospitalizations (p < 0.0001) and among adults, the rate of CDI was four times greater in IBD than non-IBD hospitalizations (p < 0.0001). In adults, CDI was significantly higher in ulcerative colitis (UC) than Crohn's disease (60.4 per 1,000 vs. 19.8 per 1,000, p < 0.0001) but in children there was no difference in CDI in UC compared with Crohn's disease (32 per 1,000 vs. 27 per 1,000, p = 0.45). The prevalence of CDI increased in pediatric and adult IBD patients, and patients without IBD, between 1993 and 2012 (p for trend <0.0001). CONCLUSIONS: CDI was more common in adult patients with UC, and no difference was found between CDI and IBD type in pediatrics. There may be different risk factors for CDI during hospitalization between adults and children with IBD.

Chronic diarrhea, ascites, and protein-losing enteropathy in an infant with hepatic venous outflow obstruction after liver transplantation.

An 18-month-old female status post-orthotopic liver transplant for biliary atresia presented nine months after transplant with severe diarrhea and intolerance of feeds. She was found to have a PLE as evidenced by a low serum albumin and a persistent elevation of fecal A1AT. Investigation eventually revealed that the cause of the PLE was a stricture at the anastomosis site between the hepatic vein and inferior cava, supported by resolution of the PLE after venoplasty of the stricture. The patient has subsequently required several repeat venoplasties for recurrence of her symptoms correlating with recurrence of the stricture. This is a very rare presentation of hepatic venous outflow obstruction. Moreover, normal duplex ultrasound imaging of liver vasculature and her unusual presentation led to a delay in her diagnosis highlighting the need for an increased index of suspicion.

Positive effects of exercise on falls and fracture risk in osteopenic women.

UNLABELLED: Exercise may affect osteopenic women at risk of falls and fractures. A workstation approach to exercise was evaluated in a randomised study of 98 women. The intervention group improved in measures of balance, strength and bone density. This study supports a preventative exercise approach that aims to reduce risk factors for fractures and falls, in women already at risk, through balance training and weight-bearing activity. INTRODUCTION: The objective of this study was to determine the effects of a workstation balance training and weight-bearing exercise program on balance, strength and bone mineral density (BMD) in osteopenic women. A single-blinded randomised controlled trial (RCT) was undertaken for 20 weeks with measurements at baseline and completion. MATERIALS AND METHODS: Ninety-eight (98) community-dwelling osteopenic women aged 41-78 years were recruited through the North Brisbane electoral roll. Subjects were randomised via computer-generated random numbers lists into either a control (receiving no intervention), or exercise group (two one-hour exercise sessions per week for 20 weeks with a trained physiotherapist). Assessments at baseline and post-intervention included balance testing (five measures), strength testing (quadriceps, hip adductors / abductors / external rotators and trunk extensors), and DXA scans (proximal femur and lumbar spine). Baseline assessment showed no significant differences between groups for all demographics and measures except for subjects taking osteoporosis medication. The percentage differences between pre- and post-intervention measurements were examined for group effect by ANOVA using an intention-to-treat protocol. RESULTS: Ninety-eight women (mean age 62.01 years, SD 8.9 years) enrolled in the study. The mean number of classes attended for the 42 participants in the exercise group who completed the program was 28.2 of a possible 40 classes (71%). At the completion of the trial the intervention group showed markedly significant better performances in balance (unilateral and bilateral stance sway measures, lateral reach, timed up and go and step test) (p < 0.05) with strong positive training effects reflecting improvements of between 10% to 71%. Similarly there were gains in strength of the hip muscles (abductors, adductors, and external rotators), quadriceps and trunk extensors with training effects between 9% and 23%. CONCLUSIONS: Specific workstation exercises can significantly improve balance and strength in osteopenic women. This type of training may also positively influence bone density although further study is required with intervention over a longer period. A preventative exercise program may reduce the risk of falls and fractures in osteopenic women already at risk.

Novel nuclear corticosteroid binding in rat small intestinal epithelia.

When small intestinal epithelial cells are incubated with [(3)H]corticosterone, nuclear binding is displaced neither by aldosterone nor RU-28362, suggesting that [(3)H]corticosterone is binding to a site distinct from mineralocorticoid receptor and glucocorticoid receptor. Saturation and Scatchard analysis of nuclear [(3)H]corticosterone binding demonstrate a single saturable binding site with a relatively low affinity (49 nM) and high capacity (5 fmol/microg DNA). Competitive binding assays indicate that this site has a unique steroid binding specificity, which distinguishes it from other steroid receptors. Steroid specificity of nuclear binding mirrors inhibition of the low 11beta-dehydrogenase activity, suggesting that binding may be to an 11beta-hydroxysteroid dehydrogenase (11betaHSD) isoform, although 11betaHSD1 is not present in small intestinal epithelia and 11betaHSD2 does not colocalize intracellularly with the binding site. In summary, a nuclear [(3)H]corticosterone binding site is present in small intestinal epithelia that is distinct from other steroid receptors and shares steroid specificity characteristics with 11betaHSD2 but is distinguishable from the latter by its distinct intracellular localization.