OBJECTIVE-Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low-birth-weight (<1000 g) infants. We quantify risk factors predicting infection in high-risk premature infants and compare clinical judgment with a prediction model of invasive candidiasis. METHODS-The study involved a prospective observational cohort of infants <1000 g birth weight at 19 centers of the NICHD Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: 1) potentially modifiable risk factors and 2) a clinical model at time of blood culture to predict candidiasis.RESULTS-Invasive candidiasis occurred in 137/1515 (9.0%) infants and was documented by positive culture from ≥ 1 of these sources: blood (n=96), cerebrospinal fluid (n=9), urine obtained by catheterization (n=52), or other sterile body fluid (n=10). Mortality was not different from infants who had positive blood culture compared to those with isolated positive urine culture. Incidence varied from 2-28% at the 13 centers enrolling ≥ 50 infants. Potentially modifiable risk factors (model 1) included central catheter, broad-spectrum antibiotics (e.g., third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model (model 2) had an area under the receiver operating characteristic curve of 0.79, and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis. Performance of clinical judgment did not vary significantly with level of training. CONCLUSION-Priorantibiotics, presence of a central catheter, endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment. KeywordsCandidiasis; premature infant; risk factors In the extremely low-birth-weight (ELBW; <1000g) infant, invasive candidiasis is common, often fatal, and frequently leads to poor neurodevelopmental outcomes. 1,2 Invasive candidiasis (Candida infections of the blood and other sterile body fluids) is the second most common cause of infectious disease-related death in the extremely premature infant. Despite antifungal treatment, 20% of infants who develop invasive candidiasis die, and neurodevelopmental impairment occurs in nearly 60% of survivors. 1,2 Rates of invasive candidiasis vary 10-fold among similar academic tertiary care neonatal intensive care units (NICUs). 3 This variation among nurseries is found throughout the world 4-9 and has not been explained, but exposure to environmental risk factors (e.g., incubator humidity), third-generation cephalosporins, and foreign bodies such as catheters have all been associated with development of disease. 3,10,11 The high morbidity related to invasive candidiasis leads to the consideration of empirical anti...

BACKGROUND-Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families. METHODS-We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences.

Objectives To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates. Study design This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network’s Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 240/7 to 276/7 weeks’ gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation. Results Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/bronchopulmonary dysplasia (OR 3.27). Conclusions Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities. Trial registration ClinicalTrials.gov: NCT00233324.

Background Late-onset sepsis (LOS) is an important cause of death and neurodevelopmental impairment in premature infants. The purpose of this study was to assess overall incidence of LOS, distribution of LOS-causative organisms, and center variation in incidence of LOS for extremely premature infants over time. Methods In a retrospective analysis of infants 401–1000 g birth weight and 22–28 6/7 weeks’ gestational age born at 12 NICHD Neonatal Research Network centers in the years 2000–2005 (Era 1) or 2006–2011 (Era 2) who survived >72 hours, we compared the incidence of LOS and pathogen distribution in the 2 eras using the chi-square test. We also examined the effect of birth year on the incidence of LOS using multivariable regression to adjust for non-modifiable risk factors and for center. To assess whether the incidence of LOS was different among centers in Era 2, we used a multivariable regression model to adjust for non-modifiable risk factors. Results 10,131 infants were studied. LOS occurred in 2083/5031 (41%) infants in Era 1 and 1728/5100 (34%) infants in Era 2 (P<.001). Birth year was a significant predictor of LOS on adjusted analysis, with birth years 2000–2009 having a significantly higher odds of LOS than the reference year 2011. Pathogens did not differ, with the exception of decreased fungal infection (P<.001). In Era 2, nine centers had significantly higher odds of LOS compared with the center with the lowest incidence. Conclusions The incidence of LOS decreased over time. Further investigation is warranted to determine which interventions have the greatest impact on infection rates.