Blood group AB increases risk for surgical necrotizing enterocolitis and focal intestinal perforation in preterm infants with very low birth weight.

Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07-2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06-3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10-2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.

Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants.

BACKGROUND: Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. METHODS: In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. RESULTS: We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. CONCLUSIONS: Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

Differential expression of the B cell-restricted molecule CD22 on neonatal B lymphocytes depending upon antigen stimulation.

Newborns respond poorly to certain antigens and produce mainly IgM antibodies. By flow cytometry we analyzed on neonatal and adult B cells the expression of CD22, a B cell receptor (BCR)-associated membrane molecule, known as negative modulator of BCR signaling. After T cell-independent (TI-)stimulation with anti-mu F(ab')(2) fragments we found a dramatic decrease in the percentage of neonatal CD22(+) B cells and CD22 mean fluorescence intensity (MFI) shift, whereas adult B cells remained unaffected. Survival and proliferation rates of neonatal B cells were higher compared to adult B cells whereas the degrees of apoptosis and necrosis were comparable. Surprisingly, after stimulation with lower doses of anti-mu apoptosis as well as proliferation increased significantly in contrast to adult B cells. T cell-dependent (TD)-stimulation with anti-CD40 monoclonal antibody and IL-4 resulted in a dramatic increase in the percentage of CD22(+) neonatal B cells in contrast to unaffected adult B cells. CD22 MFI shifts showed no significant changes, respectively. The survival rate was higher for adult B cells, whereas apoptosis and cell death were comparable. These results suggest that TI antigens lower the neonatal BCR signaling threshold via down-regulation of CD22, resulting in hyperresponsive B cells apt to premature apoptosis. On the other hand, up-regulation of CD22 after TD stimulation may allow increased inhibiting influence of CD22 on neonatal BCR signaling, impairing B cell activation and differentiation.