IMPORTANCE Excessive antibiotic use has been associated with altered bacterial colonization and may result in antibiotic resistance, fungemia, necrotizing enterocolitis (NEC), and mortality. Exploring the association between antibiotic exposure and neonatal outcomes other than infection-related morbidities may provide insight on the importance of rational antibiotic use, especially in the setting of culture-negative neonatal sepsis. OBJECTIVE To evaluate the trend of antibiotic use among all hospitalized very low-birth-weight (VLBW) infants across Canada and the association between antibiotic use rates (AURs) and mortality and morbidity among neonates without culture-proven sepsis or NEC. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted among VLBW infants (<1500 g) admitted to level III neonatal intensive care units between January 1, 2010, and December 31, 2014, using data obtained from the Canadian Neonatal Network database. EXPOSURE Duration of antibiotic use during the hospitalization period. MAIN OUTCOMES AND MEASURES The AUR was defined as the number of days an infant was exposed to 1 or more antimicrobial agents divided by the total length of hospital stay. The composite primary outcome was defined as mortality or major morbidity, including any of the following: persistent periventricular echogenicity or echolucency on neuroimaging, chronic lung disease, and stage 3 or higher retinopathy of prematurity. Multivariable regression analysis was used to calculate adjusted odds ratios (aORs) and 95% CIs for the association between AURs and outcomes. RESULTS Among 13 738 eligible VLBW infants, 11 669 (84.9%) (mean [SD] gestational age, 27.7 [2.5] weeks; 47.4% female) received antibiotics during their hospital course and were included in the study. The annual AUR decreased from 0.29 in 2010 to 0.25 in 2014 (slope for the best-fit line, −0.011; 95% CI, −0.016 to −0.006; P < .01), which occurred in parallel with a reduction in the rate of late-onset sepsis from 19.0% in 2010 to 13.8% in 2014 during the same period. Of the 11 669 infants who were treated with antibiotics of varying duration during their hospital stay, 2845 were diagnosed as having sepsis-related complications. Among the remaining 8824 infants without early-onset sepsis, late-onset sepsis, or NEC, a 10% increase in the AUR was associated with an increased odds of the primary composite outcome (aOR, 1.18; 95% CI, 1.13-1.23), mortality (aOR, 2.04; 95% CI, 1.87-2.21), and stage 3 or higher retinopathy of prematurity (aOR, 1.18; 95% CI, 1.06-1.32). CONCLUSIONS AND RELEVANCE Antibiotic use in VLBW infants decreased between 2010 and 2014 in Canada. However, among infants without culture-proven sepsis or without NEC, higher AURs were associated with adverse neonatal outcomes.

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Objective and methods: As the result of vigorous bubbling, infants receiving continuous positive airway pressure (CPAP) by an underwater seal (bubble CPAP) were observed to have vibrations of their chests at frequencies similar to high-frequency ventilation (HFV). We performed a randomized crossover study in 10 premature infants ready for extubation to test whether bubble CPAP contributes to gas exchange compared to conventional ventilator-derived CPAP. Measurements of tidal volume and minute volume were made using the Bear Cub neonatal volume monitor, and gas exchange was measured using an oxygen saturation monitor and a transcutaneous carbon dioxide (tcpCO₂) monitor. Results: There was a 39% reduction in minute volume (p < 0.001) and a 7% reduction in respiratory rate (p = 0.004) with no change in tcpCO₂ or O₂ saturation for infants supported with bubble versus ventilator-derived CPAP. Conclusions: The lack of difference in blood gas parameters associated with a decrease in the infant’s minute volume and respiratory rate with bubble CPAP compared with ventilator-derived CPAP suggests that the chest vibrations produced with bubble CPAP may have contributed to gas exchange. Bubble CPAP may offer an effective and inexpensive option for providing respiratory support to premature infants.