Unmyelinated white matter loss in the preterm brain is associated with early increased levels of end-tidal carbon monoxide.

Objective: Increased levels of end-tidal carbon monoxide (ETCOc) in preterm infants during the first day of life are associated with oxidative stress, inflammatory processes and adverse neurodevelopmental outcome at 2 years of age. Therefore, we hypothesized that early ETCOc levels may also be associated with impaired growth of unmyelinated cerebral white matter.

Methods: From a cohort of 156 extremely and very preterm infants in which ETCOc was determined within 24 h after birth, in 36 infants 3D-MRI was performed at term-equivalent age to assess cerebral tissue volumes of important brain regions.

Early end-tidal carbon monoxide levels, patency of the ductus arteriosus and regional cerebral oxygenation in preterm infants.

Background: Carbon monoxide (CO), a relaxant regulator of muscle tone and marker of oxidative stress and inflammation, can be measured in exhaled air by determination of end-tidal CO corrected for CO in ambient air (ETCOc).

Objective: Increased endogenous production of CO may influence patency of the ductus arteriosus, cerebral perfusion and, subsequently, cerebral oxygenation. The aim was to study the relation between early ETCOc levels, hemodynamically significant patent ductus arteriosus (hsPDA) and cerebral oxygenation (rScO2) in preterm infants <32 weeks' gestational age and determine predictive values of ETCOc for hsPDA.

Maternal and neonatal anti-cytomegalovirus IgG level and risk of postnatal cytomegalovirus transmission in preterm infants.

Immunological mechanisms influencing the risk of mother-to-child cytomegalovirus (CMV) transmission in preterm infants have not been studied sufficiently. In this study, the correlation between maternal and neonatal serum anti-CMV IgG levels and risk of postnatal CMV transmission in preterm infants was assessed. Anti-CMV IgG levels of 79 CMV seropositive mothers and their 94 infants were determined in peripheral blood samples collected within 3 days after delivery.

Cerebral white matter and neurodevelopment of preterm infants after coagulase-negative staphylococcal sepsis.

Objective: Coagulase-negative staphylococci are the most common pathogens causing late-onset sepsis in the neonatal intensive care unit. Neonatal sepsis can be associated with cerebral white matter damage in preterm infants. Neurodevelopment has been shown to be correlated with apparent diffusion coefficients, fractional anisotropy, and axial and radial diffusivities of the white matter.

The effect of a computerized prescribing and calculating system on hypo- and hyperglycemias and on prescribing time efficiency in neonatal intensive care patients.

Background: Prescribing glucose requires complex calculations because glucose is present in parenteral and enteral nutrition and drug vehicles, making it error prone and contributing to the burden of prescribing errors.

Objective: Evaluation of the impact of a computerized physician order entry (CPOE) system with clinical decision support (CDS) for glucose control in neonatal intensive care patients (NICU) focusing on hypo- and hyperglycemic episodes and prescribing time efficiency.

Methods: An interrupted time-series design to examine the effect of CPOE on hypo- and hyperglycemias and a crossover simulation study to examine the influence of CPOE on prescribing time efficiency.

Reduced expression of PBP-2A by neonatal mecA-positive coagulase-negative staphylococci (CoNS) blood isolates: β-lactams are useful first-line agents for the treatment of neonatal CoNS sepsis, restricting the use of vancomycin.

Objectives: Vancomycin use for neonatal coagulase-negative staphylococci (CoNS) sepsis is based on a high CoNS carriage rate of mecA, encoding penicillin-binding protein (PBP)-2a, with low affinity for, and associated with resistance to, β-lactam antibiotics. The relationship between mecA gene carriage, phenotypic expression of the gene by PBP-2a production and in vitro resistance to the β-lactam antibiotics oxacillin, cefazolin and amoxicillin/clavulanate was determined for 85 CoNS blood isolates randomly obtained from our collection of isolates from neonates with CoNS sepsis.

Methods: The relationship between mecA gene carriage, phenotypic expression of the gene by PBP-2a production and in vitro resistance to the β-lactam antibiotics oxacillin, cefazolin and amoxicillin/clavulanate was determined for randomly obtained CoNS blood isolates from our collection of isolates from neonates with CoNS sepsis.

Shortening the antibiotic course for the treatment of neonatal coagulase-negative staphylococcal sepsis: fine with three days?

Background: The incidence of coagulase-negative staphylococcal (CoNS) sepsis is high in neonatal intensive care units (NICUs) and treatment significantly adds to the antibiotic pressure, increasing the threat of resistance. Because infants recover within 24-48 h, blood cultures are negative within 48 h and CRP normalizes within 72 h, we reduced anti-CoNS treatment from 7 to 3 days in infants with uncomplicated CoNS sepsis.

Objectives: The aim of the study was to evaluate the effect of short (3 days) treatment duration for CoNS sepsis.

Early end-tidal carbon monoxide levels and neurodevelopmental outcome at 3 years 6 months of age in preterm infants.

Aim: Increased end-tidal carbon monoxide (ETCOc) and cytokines in preterm infants are related to bronchopulmonary dysplasia and intraventricular haemorrhages. The aim was to study the predictive value of ETCOc and cytokine levels for long-term outcome.

Methods: This study comprised 105 very preterm infants (57 males, 48 females; gestational age range 25 wks 5d-31 wks 4d; birthweight 610-2100 g) who were admitted to a neonatal intensive care unit between 1 February and 31 December 2002.

A seven-year survey of management of coagulase-negative staphylococcal sepsis in the neonatal intensive care unit: vancomycin may not be necessary as empiric therapy.

Background: The typical empiric therapy for coagulase-negative staphylococcal (CONS) sepsis includes vancomycin. In our neonatal intensive care unit, we have consistently avoided the use of vancomycin to treat CONS sepsis, except for specific cases, and have used instead cefazolin as empiric agent.

Objectives: The clinical outcome of infants with CONS sepsis was evaluated in relation to the susceptibility of CONS blood isolates to cefazolin over a period of 7 years.

Prevention of neonatal late-onset sepsis associated with the removal of percutaneously inserted central venous catheters in preterm infants.

Objectives: Indwelling central venous catheters are the most important risk factors for the development of sepsis attributable to coagulase-negative staphylococci among preterm infants admitted to neonatal intensive care units. In addition, removal of a central venous catheter also may cause coagulase-negative staphylococci sepsis, which may be prevented by the short-term administration of an anti-staphylococcal agent during the procedure of removal. The administration of a specific anti-staphylococcal agent (cefazolin) was evaluated for the prevention of central venous catheter removal-associated coagulase-negative staphylococci sepsis.

Improvement of adherence to hand hygiene practice using a multimodal intervention program in a neonatal intensive care.

Nosocomial infections are serious complications among preterm infants admitted to neonatal intensive care units (NICU). Hand hygiene is one of the most effective measures to prevent these infections. This study, performed in a tertiary level NICU, highlights the importance of a multimodal intervention program for adherence to hand hygiene.

Prognosis for neonates with enterovirus myocarditis.

Objective: To assess the severity of the disease and the long-term cardiac prognosis for neonates who developed enterovirus (EV) myocarditis within the first weeks of life.

Design: Clinical presentation, echocardiographic and ECG findings and the outcome of seven infants with EV myocarditis admitted to the intensive care unit are reported. Additionally, 28 previously reported cases are described.

Variation in antibiotic use in neonatal intensive care units in the Netherlands.

Objectives: To examine the variation in quantity and classes of antibiotics used in all 10 tertiary care neonatal intensive care units (NICUs) in the Netherlands during 2005.

Methods: We collected data from all tertiary care NICUs in the Netherlands on clinical and demographic characteristics and the type and quantity of systemic antibiotic use [expressed as defined daily doses (DDD)/100 admissions] in 2005. Antibiotics were ranked by volume of DDDs, and those antibiotics which accounted for 90% of the total volume of use [drug utilization (DU) 90%] were noted.

Human rhinovirus causes severe infection in preterm infants.

Data of 11 infants (median gestational age and birth weight 30 weeks and 1520 g, respectively) with severe human rhinovirus infection (HRV) are described. Nine of 11 (82%) were preterm infants and 7 of these 9 (78%) became infected during their stay in the neonatal intensive care unit. All infants presented with respiratory distress and all needed respiratory support for a median of 6 days.

Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents.

Background: In an era with increased maternal antibiotic use, patterns in early- and late-onset sepsis and antibiotic susceptibility may have changed.

Objectives: To identify longitudinal trends in causative microorganisms for neonatal sepsis and analyze antibiotic susceptibility of all blood isolates of infants with sepsis.

Methods: Early- and late-onset sepsis cases from 29 years (1978-2006) were studied retrospectively, in five clusters of 5 years (period I-V) and one cluster of 4 years (period VI), including antibiotic susceptibility profiles of blood isolates during the years 1999-2006.

Removal of percutaneously inserted central venous catheters in neonates is associated with the occurrence of sepsis.

Background: Clinical signs of sepsis are frequently observed after removal of a percutaneously inserted central venous catheter (PCVC) in neonates admitted at our Neonatal Intensive Care Unit (NICU). To substantiate this finding and to evaluate the effect of antibiotics administered at the time of removal of a PCVC, we conducted a retrospective study among all infants with a PCVC, admitted at our NICU during 2002 and 2005.

Methods: Clinical data, infectious complications and use of antibiotics were studied retrospectively.

Oxidative stress and proinflammatory cytokine levels are increased in premature neonates of preeclamptic mothers with HELLP syndrome.

Background: Respiratory distress syndrome (RDS) incidence is increased in infants of preeclamptic mothers with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative stress and inflammatory processes.

Objectives: We hypothesize that end-tidal carbon monoxide corrected for inhaled CO (ETCOc), malondialdehyde (MDA) (markers of oxidative stress) and proinflammatory cytokine (IL-6, IL-8) production are higher in infants of preeclamptic mothers with HELLP syndrome than in those of preeclamptic mothers without HELLP syndrome.

Severe neonatal parechovirus infection and similarity with enterovirus infection.

Background: Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae. Less is known about severe neonatal infection caused by the parechoviruses (PeV) of which type 1 (PeV1) and type 2 (PeV2) were previously known as echovirus 22 and echovirus 23. They belong to the same family of Picornaviridae as the EV.

Toll-like receptor 2 polymorphism is associated with preterm birth.

Evidence is increasing for a role of polymorphisms in maternal or fetal innate immune response genes in preterm birth. Toll-like receptors (TLRs) are important receptors in the innate immunity. The genotype distribution of two TLR2 single nucleotide polymorphisms (SNPs) and one TLR4 SNP were determined among 524 neonates and associated with gestational age (GA).

Innate immunity: toll-like receptors and some more. A brief history, basic organization and relevance for the human newborn.

The discovery of Toll-like receptors (TLRs) as essential components of the innate immune system has greatly advanced our knowledge and understanding of immune responses to infection and how these are regulated. Innate immunity in general and TLRs in particular play a crucial role in the front line of host defenses against microbes, but also are a key element in the proper functioning of the immune system at large in vertebrate animals. The innate immune system has been identified as a collection of factors, both cell-associated and cell-free, that comprises an impressively effective and well-organized system that is capable of immediate recognition of a whole array of microbes and microbial components.

End-tidal carbon monoxide measurements in infant respiratory distress syndrome.

Background: RDS involving inflammatory and oxidative processes may lead to increased production of carbon monoxide (CO).

Aim: The relationship between end-tidal CO, corrected for inhaled CO (ETCOc), and RDS severity was investigated in preterm infants as well as the value of early ETCOc measurements to predict chronic lung disease.

Methods: 78 infants (30 no RDS, 32 moderate RDS, 16 severe RDS) were included.

Respiratory distress syndrome-associated inflammation is related to early but not late peri/intraventricular hemorrhage in preterm infants.

Objective: To investigate whether or not peri/intraventricular hemorrhages (PIVHs) occurring in the first 12 hours of life (early PIVHs) are related to respiratory distress syndrome (RDS)-associated inflammatory factors in contrast to PIVHs developing after 12 hours of life (late PIVHs).

Study Design: Blood samples obtained at 0 to 12 hours, 48 to 72 hours, and 168 hours of life were evaluated for determination of the proinflammatory cytokines interleukin (IL)-8 and IL-6, tumor necrosis factor (TNF)-alpha, and malondialdehyde (MDA) as measures of lipid peroxidation. Simultaneously, cranial ultrasonography was performed in 114 neonates under 32 weeks gestational age.

Inflammatory mediators for the diagnosis and treatment of sepsis in early infancy.

Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls.