A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants.

Background: The genetic basis of sepsis susceptibility in preterm infants remains understudied. Herein, we investigated the nucleotide binding-oligomerization domain (NOD)-like receptor (NLR) family of immune receptors as putative loci for preterm sepsis susceptibility.

Objective: To determine whether single nucleotide polymorphisms (SNPs) in NLR genes are associated with blood stream infections (BSI) in premature infants.

A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants.

Background: The genetic basis of dysfunctional immune responses in necrotizing enterocolitis (NEC) remains unknown. We hypothesized that variants in nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) and autophagy (ATG) genes modulate vulnerability to NEC.

Methods: We genotyped a multi-center cohort of premature infants with and without NEC for NOD1, NOD2, ATG16L1, CARD8, and NLRP3 variants.

Necrotizing Enterocolitis Is Not Associated With Sequence Variants in Antioxidant Response Genes in Premature Infants.

Reactive oxygen species mediate intestinal injury in necrotizing enterocolitis (NEC), and yet the contribution of antioxidant response (ARE) gene polymorphisms to NEC risk remains unknown. Premature infants recruited in a multicenter study were genotyped for 6 ARE variants. Among 637 infants, 52 had NEC, and 22 developed surgical NEC.

The effect of dimethyl fumarate (Tecfidera™) on lymphocyte counts: A potential contributor to progressive multifocal leukoencephalopathy risk.

Dimethyl fumarate (Tecfidera™) is an effective therapy for relapsing forms of multiple sclerosis (MS). Our study suggests that this drug may have immunosuppressive properties evidenced by significant sustained reduction in CD8 lymphocyte counts and, to a lesser extent, CD4 lymphocyte counts. This observation is relevant in light of the recent case of progressive multifocal leukoencephalopathy in a patient receiving this drug.

Antioxidant response genes sequence variants and BPD susceptibility in VLBW infants.

Background: Lung injury resulting from oxidative stress contributes to bronchopulmonary dysplasia (BPD) pathogenesis. Nuclear factor erythroid-2 related factor-2 (NFE2L2) regulates cytoprotective responses to oxidative stress by inducing enzymes containing antioxidant response elements (ARE). We hypothesized that ARE genetic variants will modulate susceptibility or severity of BPD in very-low-birth-weight (VLBW) infants.

A TLR5 (g.1174C > T) variant that encodes a stop codon (R392X) is associated with bronchopulmonary dysplasia.

Current evidence supports a major role for inherited factors in determining bronchopulmonary dysplasia (BPD) susceptibility. The Toll-like receptor (TLR) family of proteins maintain pulmonary homeostasis in the developing lung by aiding pathogen recognition and clearance, regulating inflammation, and facilitating reparative tissue growth. We hypothesized that sequence variation in the TLR pathway genes would alter the susceptibility/severity of BPD in preterm infants.

Safety of percutaneous endoscopic gastrostomy in medically complicated infants.

Background And Objective: Percutaneous endoscopic gastrostomy (PEG) tubes have been placed in children for more than 2 decades to provide nutrition to those unable to adequately and safely feed orally. Despite the well-documented success of PEG placement in older children, there is only 1 published article documenting the safety of PEG placement in small infants. In all children, PEG studies demonstrate the major complication rate to vary from 0.

The NFKB1 (g.-24519delATTG) variant is associated with necrotizing enterocolitis (NEC) in premature infants.

Objective: While it is known that gene-environment interactions contribute to necrotizing enterocolitis (NEC) pathogenesis, characterization of genetic risk-factors that can predict NEC in preterm infants remains nascent. We hypothesized that altered intestinal immune responses arising from sequence variation in the toll-like receptor (TLR) pathway genes contribute to NEC susceptibility.

Materials And Methods: Very low birth weight (VLBW) infants were recruited prospectively in a multi-center, cohort study involving collection of blood samples along with collation of clinical information.

Strategies to prevent ventilator-associated pneumonia in neonates.

Ventilator-associated pneumonia (VAP) is one of the leading causes of preventable morbidity and mortality in neonatal intensive care units. This review examines the epidemiology and pathogenesis of VAP in neonates as well as the dilemmas faced by caregivers to diagnose and prevent VAP.

Strategies to prevent bacterial and fungal infection in the neonatal intensive care unit.

Hospital-acquired infections are one of the leading causes of preventable morbidity and mortality in neonatal intensive care units (NICUs). Device-related infections, such as catheter-associated blood stream infections (CABSIs) and ventilator-associated pneumonia (VAP), are the most common nosocomial infections. This review examines the pathogenesis of CABSIs and methods, widely accepted and novel, that can be used to help prevent them.

Cohort study of the pathogenesis and molecular epidemiology of catheter-related bloodstream infection in neonates with peripherally inserted central venous catheters.

Objective: To better define the pathogenesis of catheter-related bloodstream infection (BSI) in neonates with peripherally inserted central venous catheters (PICCs) to guide the development of more effective strategies for prevention.

Design: Prospective nested cohort study.

Setting: Level III neonatal intensive care unit in a community hospital.

The effect of a prolonged time interval between antenatal corticosteroid administration and delivery on outcomes in preterm neonates: a cohort study.

Objective: This study was undertaken to determine whether the neonatal benefit of a single complete course of antenatal corticosteroids diminishes when delivery is remote from administration (> 14 days).

Study Design: This retrospective 2 center cohort trial included women who received a single complete course of antenatal corticosteroids and delivered a viable singleton infant between 26 and 34 weeks of gestation. Patients were divided into 1 of 2 groups on the basis of the interval from first corticosteroid dose to delivery (2-14 days and > 14 days).

Effect of dose on response to adrenocorticotropin in extremely low birth weight infants.

Context: Various cosyntropin doses are used to test adrenal function in premature infants, without consensus on appropriate dose or adequate response.

Objective: The objective of this study was to test the cortisol response of extremely low birth weight infants to different cosyntropin doses and evaluate whether these doses differentiate between groups of infants with clinical conditions previously associated with differential response to cosyntropin.

Design: The design was a prospective, nested study conducted within a randomized clinical trial of low-dose hydrocortisone from November 1, 2001, to April 30, 2003.

A vancomycin-heparin lock solution for prevention of nosocomial bloodstream infection in critically ill neonates with peripherally inserted central venous catheters: a prospective, randomized trial.

Objective: Critically ill neonates are at high risk for vascular catheter-related bloodstream infection (CRBSI), most often caused by coagulase-negative staphylococci. Most CRBSIs with long-term devices derive from intraluminal contaminants. The objective of this study was to ascertain the safety and the efficacy of a vancomycin-heparin lock solution for prevention of CRBSI.

Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial.

Background: Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks' postmenstrual age, particularly in infants exposed to histologic chorioamnionitis.

Methods: Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between 12 and 48 hours of life.