Evaluation of neutropenia and neutrophilia in preterm infants

OBJECTIVE: Neutrophil counts are used routinely as part of the sepsis evaluation in newborn infants. In this article, we review the normal blood neutrophil concentrations and the clinical approach to neutropenia and neutrophilia in the neonatal period. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Neutropenia and neutrophilia are documented frequently in premature infants. Neutropenia can be seen in up to 8% of all infants admitted to neonatal intensive care. Neutrophilia is even more common, reported in up to 40% of all preterm infants. CONCLUSIONS: Neutrophil counts should be carefully evaluated in premature neonates. Maternal and perinatal history, physical examination, and a limited laboratory assessment is usually adequate for making a diagnosis in most infants

Association between red cell transfusions and necrotizing enterocolitis

OBJECTIVE: Several case reports and retrospective studies have reported a temporal association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC). In this article, we review the clinical evidence and biological plausibility of the association between RBC transfusions and NEC. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Among all cases of NEC, 25 -40% patients were noted to have received an RBC transfusion within a 48 hour period prior to onset of NEC. Compared to infants who developed NEC unrelated to transfusion, neonates with transfusion-associated NEC were born at an earlier gestation, had lower birth weights, and had a delayed onset at 3-5 weeks of postnatal age. CONCLUSIONS: Based on current clinical evidence, transfusion-associated NEC appears to be a plausible clinical entity. However, there is a need for cautious interpretation of data because all the studies that have been conducted until date are retrospective, and therefore, susceptible to bias. A large, prospective, multi-center trial is needed to evaluate the association between RBC transfusion and NEC

Dichotomous development of the gut microbiome in preterm infants.

BackgroundPreterm infants are at risk of developing intestinal dysbiosis with an increased proportion of Gammaproteobacteria. In this study, we sought the clinical determinants of the relative abundance of feces-associated Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was characterized at ≤ 2 weeks and during the 3rd and 4th weeks after birth, by 16S rRNA amplicon sequencing. Maternal and infant clinical characteristics were extracted from electronic medical records. Data were analyzed by linear mixed modeling and linear regression.ResultsClinical data and fecal microbiome profiles of 45 VLBW infants (gestational age 27.9 ± 2.2 weeks; birth weight 1126 ± 208 g) were studied. Three stool samples were analyzed for each infant at mean postnatal ages of 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. The average relative abundance of Gammaproteobacteria was 42.5% (0-90%) at ≤ 2 weeks, 69.7% (29.9-86.9%) in the 3rd, and 75.5% (54.5-86%) in the 4th week (p < 0.001). Hierarchical and K-means clustering identified two distinct subgroups: cluster 1 started with comparatively low abundance that increased with time, whereas cluster 2 began with a greater abundance at ≤ 2 weeks (p < 0.001) that decreased over time. Both groups resembled each other by the 3rd week. Single variants of Klebsiella and Staphylococcus described variance in community structure between clusters and were shared between all infants, suggesting a common, hospital-derived source. Fecal Gammaproteobacteria was positively associated with vaginal delivery and antenatal steroids.ConclusionsWe detected a dichotomy in gut microbiome assembly in preterm infants: some preterm infants started with low relative gammaproteobacterial abundance in stool that increased as a function of postnatal age, whereas others began with and maintained high abundance. Vaginal birth and antenatal steroids were identified as predictors of Gammaproteobacteria abundance in the early (≤ 2 weeks) and later (3rd and 4th weeks) stool samples, respectively. These findings are important in understanding the development of the gut microbiome in premature infants

Probiotic Bacteria Induce Maturation of Intestinal Claudin 3 Expression and Barrier Function

An immature intestinal epithelial barrier may predispose infants and children to many intestinal inflammatory diseases, such as infectious enteritis, inflammatory bowel disease, and necrotizing enterocolitis. Understanding the factors that regulate gut barrier maturation may yield insight into strategies to prevent these intestinal diseases. The claudin family of tight junction proteins plays an important role in regulating epithelial paracellular permeability. Previous reports demonstrate that rodent intestinal barrier function matures during the first 3 weeks of life. We show that murine paracellular permeability markedly decreases during postnatal maturation, with the most significant change occurring between 2 and 3 weeks. Here we report for the first time that commensal bacterial colonization induces intestinal barrier function maturation by promoting claudin 3 expression. Neonatal mice raised on antibiotics or lacking the toll-like receptor adaptor protein MyD88 exhibit impaired barrier function and decreased claudin 3 expression. Furthermore, enteral administration of either live or heat-killed preparations of the probiotic Lactobacillus rhamnosus GG accelerates intestinal barrier maturation and induces claudin 3 expression. However, live Lactobacillus rhamnosus GG increases mortality. Taken together, these results support a vital role for intestinal flora in the maturation of intestinal barrier function. Probiotics may prevent intestinal inflammatory diseases by regulating intestinal tight junction protein expression and barrier function. The use of heat-killed probiotics may provide therapeutic benefit while minimizing adverse effects

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

Preclinical model of neonatal necrotizing enterocolitis

The disclosure provides methods of generating a murine model of neonatal necrotizing enterocolitis, whereby the generated murine animal exhibits at least one symptom of neonatal necrotizing enterocolitis. The disclosure also provides methods to measure transfusion effects on anemia and methods for identifying and isolating an agent useful for the treatment or prevention of neonatal necrotizing enterocolitis

Hematology, immunology and infectious disease : neonatology questions and controversies, 2nd edition/ Ohls

xiv, 345 hal.: ill.; tab.; 26 cm

Haematological abnormalities in neonatal necrotizing enterocolitis

OBJECTIVE: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants born prior to 32 weeks gestation or with a birth weight less than 1500 grams. In this article, we review hematological abnormalities associated with NEC. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Thrombocytopenia, disseminated intravascular coagulation, increased or decreased neutrophil counts, and hemolytic anemia are frequent events in NEC. CONCLUSIONS: NEC is associated with several hematological abnormalities, which may play a direct or indirect role in the pathogenesis of gut mucosal injury, and may also carry important prognostic information

Anemia, Red Blood Cell Transfusions, and Necrotizing Enterocolitis

In the past 15 years, multiple clinical studies have identified a temporal association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC). With some variability, most of these studies indicate that up to one-third of all cases of NEC involving very low-birth weight infants may occur within 24–48 h after receiving a RBC transfusion. There is also evidence that the risk of such transfusion-associated NEC may be higher in infants transfused with the greatest severity of anemia. In this article, we summarize the clinical evidence pertaining to these issues; specifically, the contribution of RBC transfusions, and the contribution of severity of underlying anemia, to the pathogenesis of a type of NEC potentially termed, “transfusion/anemia-associated NEC.