Infants < 90 days of age with late-onset sepsis display disturbances of the microbiome-immunity interplay.

Objective: We hypothesized that previously healthy infants < 90 days of age with late-onset sepsis (LOS) have disturbances of the gut microbiome with yet undefined specific immunological patterns.

Methods: We performed a prospective single-center convenience sample study between January 2019 and July 2021 in a case-control design. Routine diagnostics included conventional cultures (blood, cerebrospinal fluid, urine), PCRs and inflammatory markers in infants aged < 90 days with clinical LOS.

Bifidobacterium and Lactobacillus Probiotics and Gut Dysbiosis in Preterm Infants: The PRIMAL Randomized Clinical Trial.

Importance: The effects of probiotic interventions on colonization with resistant bacteria and early microbiome development in preterm infants remain to be clarified.

Objective: To examine the efficacy of Bifidobacterium longum subsp infantis, Bifidobacterium animalis subsp lactis (BB-12), and Lactobacillus acidophilus (La-5) probiotics to prevent colonization with multidrug-resistant organisms or highly epidemic bacteria (MDRO+) and to shape the microbiome of preterm infants toward the eubiotic state of healthy full-term infants.

Design, Setting, And Participants: The multicenter, double-blinded, placebo-controlled, group sequential, phase 3 Priming Immunity at the Beginning of Life (PRIMAL) randomized clinical trial, conducted from April 2018 to June 2020, included infants with gestational age of 28 to 32 weeks at 18 German neonatal units.

Reduced Humoral and Cellular Immune Response to Primary COVID-19 mRNA Vaccination in Kidney Transplanted Children Aged 5-11 Years.

The situation of limited data concerning the response to COVID-19 mRNA vaccinations in immunocom-promised children hinders evidence-based recommendations. This prospective observational study investigated humoral and T cell responses after primary BNT162b2 vaccination in secondary immunocompromised and healthy children aged 5-11 years. Participants were categorized as: children after kidney transplantation (KTx, = 9), proteinuric glomerulonephritis (GN, = 4) and healthy children (controls, = 8).

Timing of antimicrobial prophylaxis for cesarean section is critical for gut microbiome development in term born infants.

Animal models imply that the perinatal exposure to antibiotics has a substantial impact on microbiome establishment of the offspring. We aimed to evaluate the effect of timing of antimicrobial prophylaxis for cesarean section before versus after cord clamping on gut microbiome composition of term born infants. We performed an exploratory, single center randomized controlled clinical trial.

Hyperoxia/Hypoxia Exposure Primes a Sustained Pro-Inflammatory Profile of Preterm Infant Macrophages Upon LPS Stimulation.

Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O) and infections. We hypothesized that dysregulated macrophage (MФ) activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants. Therefore, we aimed to determine age-dependent differences in immune responses of monocyte-derived MФ comparing cord blood samples derived from preterm (n=14) and term (n=19) infants as well as peripheral blood samples from healthy adults (n=17) after lipopolysaccharide (LPS) exposure.

Infants Younger Than 90 Days Admitted for Late-Onset Sepsis Display a Reduced Abundance of Regulatory T Cells.

Objective: To provide epidemiological data of infants < 90 days of age with suspected late-onset sepsis (LOS) and evaluate distinct immunological specificities. We hypothesized that previously healthy infants < 3 months of age with sepsis have a yet undefined immunological predisposition; e.g.

Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants.

Regulatory T cells (Tregs) are important for the ontogenetic control of immune activation and tissue damage in preterm infants. However, the role of Tregs for the development of bronchopulmonary dysplasia (BPD) is yet unclear. The aim of our study was to characterize CD4+ CD25+ forkhead box protein 3 (FoxP3)+ Tregs in peripheral blood of well-phenotyped preterm infants ( = 382; 23 + 0 - 36 + 6 weeks of gestational age) with a focus on the first 28 days of life and the clinical endpoint BPD (supplemental oxygen for longer than 28 days of age).

Sepsis related mortality of extremely low gestational age newborns after the introduction of colonization screening for multi-drug resistant organisms.

Background: In 2013 German infection surveillance guidelines recommended weekly colonization screening for multidrug-resistant (MDRO) or highly epidemic organisms for neonatal intensive care units (NICUs) and extended hygiene measures based on screening results. It remains a matter of debate whether screening is worth the effort. We therefore aimed to evaluate sepsis related outcomes before and after the guideline update.

S100A8 and S100A9 Are Important for Postnatal Development of Gut Microbiota and Immune System in Mice and Infants.

Background & Aims: After birth, the immune system matures via interactions with microbes in the gut. The S100 calcium binding proteins S100A8 and S100A9, and their extracellular complex form, S100A8-A9, are found in high amounts in human breast milk. We studied levels of S100A8-A9 in fecal samples (also called fecal calprotectin) from newborns and during infancy, and their effects on development of the intestinal microbiota and mucosal immune system.

Pro-inflammatory cytokine ratios determine the clinical course of febrile neutropenia in children receiving chemotherapy.

Background: Febrile neutropenia is a common and serious complication during treatment of childhood cancer. Empirical broad-spectrum antibiotics are usually administered until neutrophil cell count recovery. It was the aim of this study to investigate cytokine profiles as potential biomarkers using in-vitro sepsis models to differentiate between distinct clinical courses of febrile neutropenia (FN).

Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk.

Unlabelled: : To evaluate the nutrition-related effects of prophylactic probiotics on the outcomes of preterm infants <29 weeks of gestation that receive human milk and/or formula nutrition. We hypothesize that human-milk-fed infants benefit from probiotics in terms of sepsis prevention and growth.

Methods: We performed an observational study of the German Neonatal Network (GNN) over a period of six years, between 1 January, 2013 and 31 December, 2018.

Efficacy of probiotics to prevent gut dysbiosis in preterm infants of 28+0-32+6 weeks of gestation: a randomised, placebo-controlled, double-blind, multicentre trial: the PRIMAL Clinical Study protocol.

Introduction: The healthy 'eubiosis' microbiome in infancy is regarded as the microbiome derived from term, vaginally delivered, antibiotic free, breastfed infants at 4-6 months. Dysbiosis is regarded as a deviation from a healthy state with reduced microbial diversity and deficient capacity to control drug-resistant organisms. Preterm infants are highly sensitive to early gut dysbiosis.

IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age.

Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections. The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies. This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.

Mannose-binding lectin and mannose-binding protein-associated serine protease 2 levels and infection in very-low-birth-weight infants.

Objective: The aim of this study was to explore the role of the lectin pathway in neonatal sepsis through the study of MBL and MASP2 levels and their relationship with infection in a cohort of very-low-birth-weight infants (VLBWI).

Methods: MBL and MASP2 were measured in plasma samples of n = 89 VLBWI using ELISA and correlated with clinical parameters. MBL plasma levels were aligned with genotyping data of mbl2 exon 1 polymorphisms, rs1800450, rs1800451, and rs5030737.

Low-Frequency Sensorineural Hearing Loss in Familial Hemophagocytic Lymphohistiocytosis Type 5.

Introduction: Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disease affecting the cytotoxic pathway. Due to the recent advances in molecular diagnosis, immuno-chemo therapy, and hematopoietic stem cell transplantation treatment, FHL survival rates have drastically increased.

Case Presentation: Herein, we describe a case of FHL type 5 presenting with low-frequency sensorineural hearing loss.

High Amounts of S100-Alarmins Confer Antimicrobial Activity on Human Breast Milk Targeting Pathogens Relevant in Neonatal Sepsis.

Sepsis is a leading cause of perinatal mortality worldwide. Breast milk (BM) feeding is protective against neonatal sepsis, but the molecular mechanisms remain unexplained. Despite various supplementations with potential bioactive components from BM formula feeding cannot protect from sepsis.

Lactobacillus acidophilus/Bifidobacterium infantis probiotics are associated with increased growth of VLBWI among those exposed to antibiotics.

We performed an observational study with very-low-birth weight infants (VLBWI) ≤33 weeks of gestation born in centers of the German Neonatal Network (GNN; (total n = 8534, n = 6229 received probiotics). The primary objectives of our study were (a) to assess the effect of Lactobacillus acidophilus/Bifidobacterium infantis probiotics on growth in VLBWI during primary stay in hospital and (b) to determine whether this effect is modified by antibiotic exposure. In linear regression models the administration of probiotics was independently associated with improved weight gain [g/d; effect size B = 0.

The association of mannose-binding lectin 2 polymorphisms with outcome in very low birth weight infants.

Objectives: Studies on the influence of mannose-binding lectin (MBL) deficiency on infection susceptibility in preterm infants have yielded controversial results. We investigated the association of genotype-based MBL levels with outcome in very-low-birth weight infants (VLBWI).

Methods: We genotyped 3 genetic variants of MBL2 (rs1800450, rs1800451, rs5030737) in 6878 VLBWI.

NOD2 Loss-of-Function Mutations and Risks of Necrotizing Enterocolitis or Focal Intestinal Perforation in Very Low-birth-weight Infants.

Background: NOD2 loss-of-function mutations, that is, R702W [rs2066844], G908R [rs2066845], and Leu1007fsinsC [rs5743293], have been linked to inflammatory bowel diseases. It is yet unknown whether these variants are also associated with necrotizing enterocolitis (NEC) or focal intestinal perforation (FIP) in infants of very low birth weight (VLBW).

Methods: To test this hypothesis, we genotyped 9082 VLBW infants with European ancestry enrolled in a prospective, population-based cohort study of the German Neonatal Network.

Preterm prelabor rupture of membranes and outcome of very-low-birth-weight infants in the German Neonatal Network.

Objective: It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation.

Design: Observational, epidemiological study design.

Setting: Population-based cohort, German Neonatal Network (GNN).

FUT 2 polymorphism and outcome in very-low-birth-weight infants.

Background: To determine whether the secretor gene fucosyltransferase (FUT)2 polymorphism G428A is predictive for adverse outcomes in a large cohort of very-low-birth weight (VLBW) infants.

Methods: We prospectively enrolled 2,406 VLBW infants from the population-based multicenter cohort of the German Neonatal network cohort (2009-2011). The secretor genotype (rs601338) was assessed from DNA samples extracted from buccal swabs.

Prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics and outcome in very low birth weight infants.

Objective: To evaluate outcome data in an observational cohort of very low birth weight infants of the German Neonatal Network stratified to prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics.

Study Design: Within the observational period (September 1, 2010, until December 31, 2012, n=5351 infants) study centers were categorized into 3 groups based on their choice of Lactobacillus acidophilus/Bifidobacterium infantis use: (1) no prophylactic use (12 centers); (2 a/b) change of strategy nonuser to user during observational period (13 centers); and (3) use before start of observation (21 centers). Primary outcome data of all eligible infants were determined according to center-specific strategy.

Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots.

Background: Purine nucleoside phosphorylase (PNP) deficiency is a rare form of autosomal recessive combined primary immunodeficiency caused by a enzyme defect leading to the accumulation of inosine, 2'-deoxy-inosine (dIno), guanosine, and 2'-deoxy-guanosine (dGuo) in all cells, especially lymphocytes. Treatments are available and curative for PNP deficiency, but their efficacy depends on the early approach. PNP-combined immunodeficiency complies with the criteria for inclusion in a newborn screening program.

Distinct mutations in STXBP2 are associated with variable clinical presentations in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL5).

Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically determined hyperinflammatory syndrome caused by uncontrolled immune response mediated by T-lymphocytes, natural killer (NK) cells, and macrophages. STXBP2 mutations have recently been associated with FHL5. To better characterize the genetic and clinical spectrum of FHL5, we analyzed a cohort of 185 patients with suspected FHL for mutations in STXBP2.