Comparison of fluconazole and nystatin oral suspensions for prophylaxis of systemic fungal infection in very low birthweight infants.

We compared the efficacy and safety of fluconazole and nystatin oral suspensions for the prevention of systemic fungal infection (SFI) in very low birthweight infants. A prospective, randomized clinical trial was conducted over a 15-month period, from May 1997 through September 1998, in 80 preterm infants with birthweights <1500 g. The infants were randomly assigned to receive oral fluconazole or nystatin, beginning within the first week of life. Prophylaxis was continued until full oral feedings were attained. Blood and urine cultures were obtained at enrollment and then weekly thereafter. Thirty-eight infants were randomly assigned to receive oral fluconazole (group I), and 42 infants were assigned to receive nystatin (group II). Birthweight, gestational age, and risk factors for fungal colonization and SFI at the time of randomization and during the hospital course were similar in both groups. SFI developed in two infants (5.3%) in group I and six infants (14.3%) in group II. The difference between these two rates was not statistically significant (relative risk, 0.37; 95% confidence interval, 0.08 to 1.72). There were no deaths in group I and six deaths in group II (P = 0.03). Two infants died of neonatal sepsis, and four deaths were related to necrotizing enterocolitis and/or spontaneous intestinal perforation. No deaths were due to SFI. Enrollment was halted before completion and the study did not attain adequate power to detect a hypothesized drop in SFI rate from 15 to 5%. Although the results cannot justify any conclusion about the relative efficacy of fluconazole versus nystatin in prevention of SFI, the significantly higher mortality rate in the nystatin group raises questions about the relative safety of this medication.

Neurodevelopmental outcome of extremely low birth weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion.

BACKGROUND AND OBJECTIVE: Extremely low birth weight infants frequently receive red cell transfusions. We sought to determine whether a restrictive versus liberal hemoglobin transfusion threshold results in differences in death or adverse neurodevelopmental outcomes of extremely low birth weight infants. PATIENTS AND METHODS: Extremely low birth weight infants previously enrolled in the Preterm Infants in Need of Transfusion Trial, a randomized, controlled trial of low versus high hemoglobin transfusion thresholds, were followed up at 18 to 21 months' corrected age. Erythrocyte transfusion was determined by an algorithm of low (restrictive) or high (liberal) hemoglobin transfusion thresholds, differing by 10 to 20 g/L and maintained until first hospital discharge. The primary composite outcome was death or the presence of cerebral palsy, cognitive delay, or severe visual or hearing impairment. RESULTS: Of 451 enrolled infants, the primary outcome was available in 430. There was no statistically significant difference in the primary outcome, found in 94 (45%) of 208 in the restrictive group and 82 (38%) of 213 in the liberal group. There were no statistically significant differences in preplanned secondary outcomes. However, the difference in cognitive delay (Mental Development Index score < 70) approached statistical significance. A posthoc analysis with cognitive delay redefined (Mental Development Index score < 85) showed a significant difference favoring the liberal threshold group. CONCLUSIONS: Maintaining the hemoglobin of extremely low birth weight infants at these restrictive rather than liberal transfusion thresholds did not result in a statistically significant difference in combined death or severe adverse neurodevelopmental outcome.

Evaluation and development of potentially better practices to reduce bronchopulmonary dysplasia in very low birth weight infants.

OBJECTIVE: The objective of this study was to describe development and implementation of potentially better practices to reduce bronchopulmonary dysplasia in very low birth weight infants (birth weight: 501-1500 g). METHODS: Results of Breathsavers Group meetings, conference calls and critically appraised topic summaries were used to construct potentially better practices. Implementation plans and experiences were reported by participants and collated. RESULTS: The Breathsavers Group developed 13 potentially better practices, based on published evidence and expert opinion. Participants determined which potentially better practices to implement and implementation methods. Participating NICUs implemented an average of 5 potentially better practices (range: 3-9). The Breathsavers Group also developed a resource kit, identified common obstacles to implementation, and initiated research to define bronchopulmonary dysplasia better. CONCLUSIONS: Multiinstitutional collaboration facilitated development and implementation of potentially better practices to reduce bronchopulmonary dysplasia.

Reduction of bronchopulmonary dysplasia after participation in the Breathsavers Group of the Vermont Oxford Network Neonatal Intensive Care Quality Improvement Collaborative.

OBJECTIVE: The objective of this study was to compare the primary and secondary outcomes of very low birth weight infants before and after participation in the Breathsavers Group of the Vermont Oxford Network-sponsored Neonatal Intensive Care Quality Collaborative. METHODS: Hospitals that participated in the Breathsavers Group contributed clinical data on the outcomes of their very low birth weight infants to the Vermont Oxford Network using standardized clinical definitions, data forms, and inclusion criteria. Outcomes from the last year of the collaborative, 2003, were compared with those from the baseline year, 2001. Models for treatment practices and outcomes measures were adjusted for within-hospital correlation (clustering) and standard risk factors that were present at birth. RESULTS: Bronchopulmonary dysplasia dropped significantly in 2003 compared with the baseline year. Survival improved but not significantly. In addition, severe retinopathy of prematurity, severe intraventricular hemorrhage, and supplemental oxygen at discharge dropped significantly. The use of conventional ventilation at any time during the initial hospitalization, postnatal steroids, and time to first dose of surfactant all decreased significantly. The use of nasal continuous positive airway pressure at any time during hospitalization increased. The use of high-frequency ventilation, delivery room intubation, and surfactant at any time during hospitalization did not change. CONCLUSIONS: The Breathsavers Group improved both clinical care processes and clinical outcomes during the Neonatal Intensive Care Quality Collaborative.

The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants.

OBJECTIVE: To determine whether extremely low birth weight infants (ELBW) transfused at lower hemoglobin thresholds versus higher thresholds have different rates of survival or morbidity at discharge. STUDY DESIGN: Infants weighing <1000 g birth weight were randomly assigned within 48 hours of birth to a transfusion algorithm of either low or high hemoglobin transfusion thresholds. The composite primary outcome was death before home discharge or survival with any of either severe retinopathy, bronchopulmonary dysplasia, or brain injury on cranial ultrasound. Morbidity outcomes were assessed, blinded to allocation. RESULTS: Four hundred fifty-one infants were randomly assigned to low (n = 223) or high (n = 228) hemoglobin thresholds. Groups were similar, with mean birth weight of 770 g and gestational age of 26 weeks. Fewer infants received one or more transfusions in the low threshold group (89% low versus 95% high, P = .037). Rates of the primary outcome were 74.0% in the low threshold group and 69.7% in the high (P = .25; risk difference, 2.7%; 95% CI -3.7% to 9.2%). There were no statistically significant differences between groups in any secondary outcome. CONCLUSIONS: In extremely low birth weight infants, maintaining a higher hemoglobin level results in more infants receiving transfusions but confers little evidence of benefit.

Evaluation and development of potentially better practices to prevent neonatal nosocomial bacteremia.

OBJECTIVE: Six neonatal intensive care units (NICUs) that are members of the Vermont Oxford National Evidence-Based Quality Improvement Collaborative for Neonatology collaborated to reduce infection rates. There were 7 centers in the original focus group, but 1 center left the collaborative after 1 year. The objective of this study was to develop strategies to decrease nosocomial infection rates in NICUs. METHODS: The process included a comprehensive literature review, internal practice analyses, benchmark studies, and development of practical experience through rapid-cycle changes, subsequent analysis, and feedback. This process led to 3 summary statements on potentially better practices in handwashing, approach to nosocomial sepsis evaluations, and central venous catheter management. RESULTS: These statements provide a basis for an evidence-based approach to lowering neonatal intensive care unit nosocomial infection rates. CONCLUSIONS: The 2-year process also led to changes in the culture and habits of the institutions involved, which should in turn have long-term effects on other aspects of quality improvement.

Trends in mortality and morbidity for very low birth weight infants, 1991-1999.

BACKGROUND: Medical care for very low birth weight (VLBW) infants and their mothers has changed dramatically during the 1990s, yet it is unclear how these changes have affected mortality and morbidity. OBJECTIVE: We used the Vermont Oxford Network Database to identify trends in clinical practice and patient outcomes for VLBW infants born from 1991 to 1999. METHODS: Logistic regression was used to evaluate temporal trends in practices and outcomes while adjusting for patient characteristics and accounting for clustering of cases within hospitals. RESULTS: There were 118 448 infants 501 to 1500 g from 362 neonatal intensive care units enrolled in the Network Database from 1991 to 1999. Prenatal care, cesarean section, multiple births, antenatal steroids, and 1-minute Apgar scores increased during this period, as did the use of nasal continuous positive airway pressure, high-frequency ventilation, surfactant, and postnatal steroids. The proportion of white infants decreased; the proportions of Hispanic infants and those of other races increased. The crude and adjusted rates of mortality, pneumothorax, intraventricular hemorrhage (IVH), and severe IVH declined from 1991 to 1995, whereas from 1995 to 1999, the rates of mortality, IVH, and severe IVH did not change significantly, and pneumothorax increased. CONCLUSIONS: There have been major changes in both obstetric and neonatal care during the 1990s. These changes were associated with decreases in mortality and morbidity for VLBW infants during the first half of the decade. However, since 1995, no additional improvements in mortality or morbidity have been seen, ending a decades-long trend of improving outcomes for these infants.