Association between intermittent hypoxemia and neurodevelopmental outcomes in extremely premature infants: A single-center experience.

OBJECTIVE: To describe the association between intermittent hypoxemic events (IHEs) and severe neurodevelopmental impairment (SNDI) or death in extremely premature infants. STUDY DESIGN: Retrospective study of extremely premature infants 230/7-276/7 weeks gestational age (GA) and birthweight (BW) ≤1250 grams (g) admitted to a level IV neonatal intensive care unit (NICU) from 2013 to 2017. IHEs, defined as events with SpO2 ≤ 80 % lasting 10 s to 5 min, were algorithmically identified using data extracted from bedside monitors at 2 s intervals (0.5 Hz). The primary outcome was SNDI at 18-24 months corrected age (CA), defined as a Bayley-III motor, language or cognitive composite score ≤69, or death before discharge while the secondary outcome was SNDI alone. We used mixed-effects regression models to evaluate the relationship between mean daily IHE rate per postnatal week of life for the first 12 weeks and the outcomes, and logistic regression models to assess the association between outcomes and summary measures of hypoxic burden for the entire NICU hospitalization. RESULTS: The mortality rate was 7 % (18/249) during NICU hospitalization. Of 249 infants born during this time period, IHE and neurodevelopmental outcome data were fully available for 65 infants (mean GA 26 ± 1.4 weeks, mean birth weight (BW) 738 ± 199 g. The outcome of SNDI alone occurred in 34 % (22/65) with a majority demonstrating motor or language delay on the Bayley-III. Although mean daily IHE rate/week was not associated with SNDI or death, total IHE duration was associated with increased odds of SNDI (OR (95 % CI) 1.03 (1.01, 1.05), p = 0.008) in models adjusted for GA. CONCLUSIONS: In a cohort of extremely premature infants 23-27 weeks GA, each hour of total IHE duration (SpO2 ≤ 80 %) was associated with a 2.7 % (0.7 %, 4.8 %) increase in the odds of SNDI at 18-24 months CA.

Antibiotic spectrum index: A new tool comparing antibiotic use in three NICUs.

BACKGROUND: Antibiotics are widely used in very low-birth-weight infants (VLBW, <1500 g), and excess exposure, particularly to broad-spectrum antibiotics, is associated with significant morbidity. An antibiotic spectrum index (ASI) quantifies antibiotic exposure by relative antimicrobial activity, adding information to exposure measured by days of therapy (DOT). We compared ASI and DOT across multiple centers to evaluate differences in antibiotic exposures. METHODS: We extracted data from patients admitted to 3 level-4 NICUs for 2 years at 2 sites and for 1 year at a third site. We calculated the ASI per antibiotic days and DOT per patient days for all admitted VLBW infants <32 weeks gestational age. Clinical variables were compared as percentages or as days per 1,000 patient days. We used Kruskal-Wallis tests to compare continuous variables across the 3 sites. RESULTS: Demographics were similar for the 734 VLBW infants included. The site with the highest DOT per patient days had the lowest ASI per antibiotic days and the site with the highest mortality and infection rates had the highest ASI per antibiotic days. Antibiotic utilization varied by center, particularly for choice of broad-spectrum coverage, although the organisms causing infection were similar. CONCLUSION: An antibiotic spectrum index identified differences in prescribing practice patterns among 3 NICUs unique from those identified by standard antibiotic use metrics. Site differences in infection rates and unit practices or guidelines for prescribing antibiotics were reflected in the ASI. This comparison uncovered opportunities to improve antibiotic stewardship and demonstrates the utility of this metric for comparing antibiotic exposures among NICU populations.

High-Frequency Positive Pressure Ventilation as Primary Rescue Strategy for Patients with Congenital Diaphragmatic Hernia: A Comparison to High-Frequency Oscillatory Ventilation.

OBJECTIVE: The aim of this article was to evaluate high-frequency positive pressure ventilation (HFPPV) compared with high-frequency oscillatory ventilation (HFOV) as a rescue ventilation strategy for patients with congenital diaphragmatic hernia (CDH). HFPPV is a pressure-controlled conventional ventilation method utilizing high respiratory rate and low positive end-expiratory pressure. STUDY DESIGN: Seventy-seven patients diagnosed with CDH from January 2005 to September 2019 who were treated with stepwise progression from HFPPV to HFOV versus only HFOV were included. Fisher's exact test and the Kruskal-Wallis test were used to compare outcomes. RESULTS: Patients treated with HFPPV + HFOV had higher survival to discharge (80 vs. 50%, p = 0.007) and to surgical intervention (95.6 vs. 68.8%, p = 0.003), with average age at repair 2 days earlier (p = 0.004). Need for extracorporeal membrane oxygenation (p = 0.490), inhaled nitric oxide (p = 0.585), supplemental oxygen (p = 0.341), and pulmonary hypertension medications (p = 0.381) were similar. CONCLUSION: In CDH patients who fail respiratory support with conventional ventilation, HFPPV may be used as an intermediary mode of rescue ventilation prior to HFOV without adverse effects. KEY POINTS: · HFPPV may be used as an intermediary mode of rescue ventilation prior to HFOV without adverse effect.. · HFPPV is more widely available and can mitigate the limitations faced when using HFOV.. · HFPPV allows for intra- or interhospital transfer of neonates with CDH..

Vital sign metrics of VLBW infants in three NICUs: implications for predictive algorithms.

BACKGROUND: Continuous heart rate (HR) and oxygenation (SpO2) metrics can be useful for predicting adverse events in very low birth weight (VLBW) infants. To optimize the utility of these tools, inter-site variability must be taken into account. METHODS: For VLBW infants at three neonatal intensive care units (NICUs), we analyzed the mean, standard deviation, skewness, kurtosis, and cross-correlation of electrocardiogram HR, pulse oximeter pulse rate, and SpO2. The number and durations of bradycardia and desaturation events were also measured. Twenty-two metrics were calculated hourly, and mean daily values were compared between sites. RESULTS: We analyzed data from 1168 VLBW infants from birth through day 42 (35,238 infant-days). HR and SpO2 metrics were similar at the three NICUs, with mean HR rising by ~10 beats/min over the first 2 weeks and mean SpO2 remaining stable ~94% over time. The number of bradycardia events was higher at one site, and the duration of desaturations was longer at another site. CONCLUSIONS: Mean HR and SpO2 were generally similar among VLBW infants at three NICUs from birth through 6 weeks of age, but bradycardia and desaturation events differed in the first 2 weeks after birth. This highlights the importance of developing predictive analytics tools at multiple sites. IMPACT: HR and SpO2 analytics can be useful for predicting adverse events in VLBW infants in the NICU, but inter-site differences must be taken into account in developing predictive algorithms. Although mean HR and SpO2 patterns were similar in VLBW infants at three NICUs, inter-site differences in the number of bradycardia events and duration of desaturation events were found. Inter-site differences in bradycardia and desaturation events among VLBW infants should be considered in the development of predictive algorithms.

Revisiting the definition of bronchopulmonary dysplasia in premature infants at a single center quaternary neonatal intensive care unit.

OBJECTIVE: To compare the incidence of bronchopulmonary dysplasia (BPD) based on the 1988 Vermont Oxford Network (VON) criteria, National Institutes of Health (NIH) 2001 definition, and NIH 2018 definition. METHODS: BPD incidence by each definition was compared in premature infants born at a single center between 2016 and 2018. Comorbidities were compared between those with and without BPD according to the newest definition. RESULTS: Among 352 survivors, BPD incidence was significantly different at 9%, 28% and 34% according to VON, NIH 2001 and NIH 2018 definitions, respectively (p < 0.05). According to the newest definition, any grade of BPD was associated with more co-morbidities than those without BPD (P < 0.001). CONCLUSION: At a center that emphasizes use of early noninvasive respiratory support, the incidence of BPD was significantly higher according to the NIH 2018 definition compared to other two definitions. The relationship between BPD diagnosis and long-term clinical outcomes remains unclear.

Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants With Late-Onset Infection.

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants. Exposures: Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.

Early hypoxemia burden is strongly associated with severe intracranial hemorrhage in preterm infants.

OBJECTIVES: The objective of this study was to define the association between the burden of severe hypoxemia (SpO2 ≤70%) in the first week of life and development of severe ICH (grade III/IV) in preterm infants. STUDY DESIGN: Infants born at <32 weeks or weighing <1500 g underwent prospective SpO2 recording from birth through 7 days. Severe hypoxemia burden was calculated as the percentage of the error-corrected recording where SpO2 ≤70%. Binary logistic regression was used to model the relationship between hypoxemia burden and severe ICH. RESULTS: A total of 163.3 million valid SpO2 data points were collected from 645 infants with mean EGA = 27.7 ± 2.6 weeks, BW = 1005 ± 291 g; 38/645 (6%) developed severe ICH. There was a greater mean hypoxemia burden for infants with severe ICH (3%) compared to those without (0.1%) and remained significant when controlling for multiple confounding factors. CONCLUSION: The severe hypoxemia burden in the first week of life is strongly associated with severe ICH.