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.

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.