Roberto Murgas Torrazza

Distortions in Development of Intestinal Microbiota Associated with Late Onset Sepsis in Preterm Infants

Late onset sepsis (LOS) is a major contributor to neonatal morbidity and mortality, especially in premature infants. Distortions in the establishment of normal gut microbiota, commensal microbes that colonize the digestive tract, might increase the risk of LOS via disruption of the mucosal barrier with resultant translocation of luminal contents. Correlation of distortions of the intestinal microbiota with LOS is a necessary first step to design novel microbiota-based screening approaches that might lead to early interventions to prevent LOS in high risk infants. Using a case/control design nested in a cohort study of preterm infants, we analyzed stool samples that had been prospectively collected from ten preterm infants with LOS and from 18 matched controls. A 16S rRNA based approach was utilized to compare microbiota diversity and identify specific bacterial signatures that differed in their prevalence between cases and controls. Overall α-diversity (Chao1) was lower in cases two weeks before (p<0.05) but not one week before or at the time of diagnosis of LOS. Overall microbiota structure (Unifrac) appeared distinct in cases 2 weeks and 1 week before but not at diagnosis (p<0.05). Although we detected few operational taxonomic units (OTUs) unique or enriched in cases, we found many OTUs common in controls that were lacking in cases (p<0.01). Bifidobacteria counts were lower in cases at all time points. Our results support the hypothesis that a distortion in normal microbiota composition, and not an enrichment of potential pathogens, is associated with LOS in preterm infants.

Intestinal Microbial Ecology and Environmental Factors Affecting Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is the most devastating intestinal disease affecting preterm infants. In addition to being associated with short term mortality and morbidity, survivors are left with significant long term sequelae. The cost of caring for these infants is high. Epidemiologic evidence suggests that use of antibiotics and type of feeding may cause an intestinal dysbiosis important in the pathogenesis of NEC, but the contribution of specific infectious agents is poorly understood. Fecal samples from preterm infants ≤32 weeks gestation were analyzed using 16S rRNA based methods at 2, 1, and 0 weeks, prior to diagnosis of NEC in 18 NEC cases and 35 controls. Environmental factors such as antibiotic usage, feeding type (human milk versus formula) and location of neonatal intensive care unit (NICU) were also evaluated. Microbiota composition differed between the three neonatal units where we observed differences in antibiotic usage. In NEC cases we observed a higher proportion of Proteobacteria (61%) two weeks and of Actinobacteria (3%) 1 week before diagnosis of NEC compared to controls (19% and 0.4%, respectively) and lower numbers of Bifidobacteria counts and Bacteroidetes proportions in the weeks before NEC diagnosis. In the first fecal samples obtained during week one of life we detected a novel signature sequence, distinct from but matching closest to Klebsiella pneumoniae, that was strongly associated with NEC development later in life. Infants who develop NEC exhibit a different pattern of microbial colonization compared to controls. Antibiotic usage correlated with these differences and combined with type of feeding likely plays a critical role in the development of NEC.

The altered gut microbiome and necrotizing enterocolitis.

Current evidence highlights the importance of developing a healthy intestinal microbiota in the neonate. Many aspects that promote health or disease are related to the homeostasis of these intestinal microbiota. Their delicate equilibrium could be strongly influenced by the intervention that physicians perform as part of the medical care of the neonate, especially preterm infants. As awareness of the importance of the development and maintenance of these intestinal flora increase and newer molecular techniques are developed, it will be possible to provide better care of infants with interventions that will have long-lasting effects.

Gastric Residual Evaluation in Preterm Neonates: A Useful Monitoring Technique or a Hindrance?

It is routine practice in most neonatal intensive care units to measure the volume and color of gastric residuals (GRs) prior to enteral bolus feedings in preterm very low birth weight infants. However, there is paucity of evidence supporting the routine use of this technique. Moreover, owing to the lack of uniform standards in the management of GRs, wide variations exist as to what constitutes significant GR volume, the importance of GR color and frequency of GR evaluation, and the color or volume standards that dictate discarding or returning GRs. The presence of large GR volumes or green-colored residuals prior to feeding often prompts subsequent feedings to be withheld or reduced because of possible necrotizing enterocolitis resulting in delays in enteral feeding. Cessation or delays in enteral feeding may result in extrauterine growth restriction, a known risk factor for poor neurodevelopmental and growth outcomes in preterm very low birth weight infants. Although some neonatal intensive care units are abandoning the practice of routine GR evaluation, little evidence exists to support the discontinuation or continuation of this practice. This review summarizes the current state of GR evaluation and underlines the need for a scientific basis to either support or refute the routine evaluation of GRs.

Decoding the enigma of necrotizing enterocolitis in premature infants

Necrotizing enterocolitis (NEC) is an enigmatic disease that affects primarily premature infants. It often occurs suddenly and when it occurs, treatment attempts at treatment often fail and results in death. If the infant survives, there is a significant risk of long term sequelae including neurodevelopmental delays. The pathophysiology of NEC is poorly understood and thus prevention has been difficult. In this review, we will provide an overview of why progress may be slow in our understanding of this disease, provide a brief review diagnosis, treatment and some of the current concepts about the pathophysiology of this disease.

The value of routine evaluation of gastric residuals in very low birth weight infants

Objective:Little information exists regarding gastric residual (GR) evaluation prior to feedings in premature infants. The purpose of this study was to compare the amount of feedings at 2 and 3 weeks of age, number of days to full feedings, growth and incidence of complications between infants who underwent RGR (routine evaluation of GR) evaluation versus those who did not.Study Design:Sixty-one premature infants were randomized to one of two groups. Group 1 received RGR evaluation prior to feeds and Group 2 did not.Result:There was no difference in amount of feeding at 2 (P=0.66) or 3 (P=0.41) weeks of age, growth, days on parenteral nutrition or complications. Although not statistically significant, infants without RGR evaluation reached feeds of 150 ml kg−1 per day 6 days earlier and had 6 fewer days with central venous access.Conclusion:Results suggest RGR evaluation may not improve nutritional outcomes in premature infants.

Aspiration and evaluation of gastric residuals in the neonatal intensive care unit: state of the science.

The routine aspiration of gastric residuals (GR) is considered standard care for critically ill infants in the neonatal intensive care unit (NICU). Unfortunately, scant information exists regarding the risks and benefits associated with this common procedure. This article provides the state of the science regarding what is known about the routine aspiration and evaluation of GRs in the NICU focusing on the following issues: (1) the use of GRs for verification of feeding tube placement, (2) GRs as an indicator of gastric contents, (3) GRs as an indicator of feeding intolerance or necrotizing enterocolitis, (4) the association between GR volume and ventilator-associated pneumonia, (5) whether GRs should be discarded or refed, (6) the definition of an abnormal GR, and (7) the potential risks associated with aspiration and evaluation of GRs. Recommendations for further research and practice guidelines are also provided.