Objective. Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 6956 VLBW (401–1500 g) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period (1998–2000). Methods. The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospective registry of all VLBW neonates admitted to participating centers within 14 days of birth. Expanded infection surveillance was added in 1998. Results. Of 6215 infants who survived beyond 3 days, 1313 (21%) had 1 or more episodes of blood culture-proven late-onset sepsis. The vast majority of infections (70%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 48% of infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus, prolonged ventilation, prolonged intravascular access, bronchopulmonary dysplasia, and necrotizing enterocolitis. Infants who developed late-onset sepsis had a significantly prolonged hospital stay (mean length of stay: 79 vs 60 days). They were significantly more likely to die than those who were uninfected (18% vs 7%), especially if they were infected with Gram-negative organisms (36%) or fungi (32%). Conclusions. Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors. Strategies to reduce late-onset sepsis and its medical, social, and economic toll need to be addressed urgently.

Late-Onset Sepsis in Very Low Birth Weight Neonates: The Experience of the NICHD Neonatal Research Network

The blood-brain barrier: an overview: structure, regulation, and clinical implications.

A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.

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Serum Procalcitonin and C-Reactive Protein Levels as Markers of Bacterial Infection: A Systematic Review and Meta-analysis

超出生体重児に対する早期デキサメサゾン投与の有用性 : National Institute of Child Health and Human Development Neonatal research Network報告 (海外誌掲載論文の和文概要とそれに対するコメント)

2010;126;e1319-e1344; originally published online Oct 18, 2010; Pediatrics COLLABORATORS CHAPTER Sithembiso Velaphi and on behalf of the NEONATAL RESUSCITATION Sam Richmond, Wendy M Simon, Nalini Singhal, Edgardo Szyld, Masanori Tamura, Chameides, Jay P Goldsmith, Ruth Guinsburg, Mary Fran Hazinski, Colin Morley, Jeffrey M Perlman, Jonathan Wyllie, John Kattwinkel, Dianne L Atkins, Leon Recommendations Resuscitation and Emergency Cardiovascular Care Science With Treatment Neonatal Resuscitation: 2010 International Consensus on Cardiopulmonary http://wwwpediatricsorg/cgi/content/full/126/5/e1319 located on the World Wide Web at: The online version of this article, along with updated information and services, is rights reserved Print ISSN: 0031-4005 Online ISSN: 1098-4275 Grove Village, Illinois, 60007 Copyright © 2010 by the American Academy of Pediatrics All and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk publication, it has been published continuously since 1948 PEDIATRICS is owned, published, PEDIATRICS is the official journal of the American Academy of Pediatrics A monthly

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Part 11: Neonatal resuscitation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

OBJECTIVES: Parenchymal involvement of intraventricular hemorrhage (IVH) is a major risk factor for neurodevelopmental handicap in very low birth weight neonates. Previous trials have suggested that indomethacin would lower the incidence and severity of IVH in very low birth weight neonates. METHODS: We enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would lower the incidence and severity of IVH. Serial cranial ultrasound examinations and echocardiographs were performed. RESULTS: There were no differences in the birth weight, gestational age, sex, Apgar scores, and percent of neonates treated with surfactant between the indomethacin and placebo groups. Within the first 5 days, 25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4 IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin-treated neonates and 29 control neonates died (P = .08); there was a difference favoring indomethacin with respect to survival time (P = .06). Eighty-six percent of all neonates had a patent ductus arteriosus on the first postnatal day; indomethacin was associated with significant ductal closure by the fifth day of life (P < .001). There were no differences in adverse events attributed to indomethacin between the two treatment groups. CONCLUSIONS: Low-dose prophylactic indomethacin significantly lowers the incidence and severity of IVH, particularly the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus arteriosus and is not associated with significant adverse drug events in very low birth weight neonates.

Low-Dose Indomethacin and Prevention of Intraventricular Hemorrhage: A Multicenter Randomized Trial

In 1960, the terms “neonatology” and “neonatologist” were introduced. Thereafter, an increasing number of pediatricians devoted themselves to full-time neonatology. In 1975, the first examination of the Sub-Board of Neonatal-Perinatal Medicine of the American Board of Pediatrics and the first meeting of the Perinatal Section of the American Academy of Pediatrics were held. One of the most important factors that improved the care of the neonate was the miniaturization of blood samples needed to determine blood gases, serum electrolytes, glucose, calcium, bilirubin, and other biochemical measurements. Another factor was the ability to provide nutrition intravenously, and the third was the maintenance of normal body temperature. The management of respiratory distress syndrome improved with i.v. glucose and correction of metabolic acidosis, followed by assisted ventilation, continuous positive airway pressure, antenatal corticosteroid administration, and the introduction of exogenous surfactant. Pharmacologic manipulation of the ductus arteriosus, support of blood pressure, echocardiography, and changes in the management of persistent pulmonary hypertension, including the use of nitric oxide and extracorporeal membrane oxygenation, all have influenced the cardiopulmonary management of the neonate. Regionalization of neonatal care; changes in parent–infant interaction; and technological changes such as phototherapy, oxygen saturation monitors, and brain imaging techniques are among the important advances reviewed in this report. Most remarkable, a 1-kg infant who was born in 1960 had a mortality risk of 95% but had a 95% probability of survival by 2000. However, errors in neonatology are acknowledged, and potential directions for the future are explored.

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The Evolution of Neonatology

Ultrasound has been routinely used since late 1979 to diagnose periventricular-intraventricular hemorrhage in infants whose gestational age was 34 weeks or less. During the years 1980 to 1987 the ultrasound scans were interpreted by one person, and a steady decline in incidence of periventricular-intraventricular hemorrhage was observed. Both for infants of 34 weeks or less and for very low birth weight (

Intraventricular Hemorrhage in Preterm Infants: Declining Incidence in the 1980s

Antenatal steroids, delivery mode, and intraventricular hemorrhage in preterm infants

Objective. To evaluate the use of a clinical pathway for neonatal sepsis in decisions about initiating and continuing antibiotic treatment. Setting. A district hospital primarily served by private pediatricians practicing in a managed care environment. Patients and Laboratory Tests. All infants admitted to the well-baby nursery in 1997–1998 were eligible for this study. Infants born with a variety of risk factors (eg, borderline prematurity, membranes ruptured for over 18 hours, mother positive for group B streptococcus [GBS], and maternal fever) or clinical manifestations suggesting possible infection (either clinical signs or persistent hypoglycemia) were evaluated with white blood cell count, differential, and C-reactive protein (CRP) soon after birth and 12 hours later. Decisions to transfer to the neonatal intensive care unit and to treat with antibiotics were based on abnormal laboratory test results, particularly an increased level of CRP (>1 mg/dL), persistent hypoglycemia, or clinical signs. Discontinuation of antibiotic treatment was primarily based on return to normal of the CRP. Results. Of 8299 live births, 7562 initially went to the well-baby nursery. Evaluation occurred in 1894 (25%) and 425 were transferred to the neonatal intensive care unit. In 162, antibiotics were discontinued within 48 hours. The majority were treated for 3 to 5 days, with only 19 (3 with GBS sepsis) treated for 6 days or more. There were 216 infants transferred because of risk factors and 209 because of clinical findings. Peak CRP primarily determined the duration of antibiotic treatment, with the mean peak CRP rising from 2.8 mg/dL in those treated for 3 days, to 3.8, 4.3, 8.4, 8.9, and 13.7 mg/dL in those treated for 4, 5, 6, 7, or >7 days, respectively. The mean duration of treatment was 3.1 days. No infant initially treated with antibiotics and discharged when the CRP returned to normal was readmitted within the next month. No infant with normal values on the sepsis screen was readmitted within 1 month with evidence of bacterial infection, but 1 infant with no risk factors was readmitted at 22 days of age with GBS sepsis and meningitis. Conclusions. Using a clinical pathway for neonatal sepsis, which is based primarily on CRP determinations, can minimize antibiotic exposure and shorten hospital stays.

https://pediatrics.aappublications.org/content/pediatrics/106/1/e4.full.pdf

Alistair G.S. Philip

Papers

Low-Dose Indomethacin and Prevention of Intraventricular Hemorrhage: A Multicenter Randomized Trial

The Evolution of Neonatology

Intraventricular Hemorrhage in Preterm Infants: Declining Incidence in the 1980s

Antenatal steroids, delivery mode, and intraventricular hemorrhage in preterm infants

Use of C-Reactive Protein in Minimizing Antibiotic Exposure: Experience With Infants Initially Admitted to a Well-Baby Nursery