The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial: study protocol for a randomized controlled trial comparing rates of extubation failure in extremely premature infants undergoing extubation to non-invasive neurally adjusted ventilatory assist versus non-synchronized nasal intermittent positive pressure ventilation.

BACKGROUND: Invasive mechanical ventilation contributes to bronchopulmonary dysplasia (BPD), the most common complication of prematurity and the leading respiratory cause of childhood morbidity. Non-invasive ventilation (NIV) may limit invasive ventilation exposure and can be either synchronized or non-synchronized (NS). Pooled data suggest synchronized forms may be superior. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) delivers NIV synchronized to the neural signal for breathing, which is detected with a specialized catheter. The DIVA (Diaphragmatic Initiated Ventilatory Assist) trial aims to determine in infants born 240/7-276/7 weeks' gestation undergoing extubation whether NIV-NAVA compared to non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV) reduces the incidence of extubation failure within 5 days of extubation. METHODS: This is a prospective, unblinded, pragmatic, multicenter phase III randomized clinical trial. Inclusion criteria are preterm infants 24-276/7 weeks gestational age who were intubated within the first 7 days of life for at least 12 h and are undergoing extubation in the first 28 postnatal days. All sites will enter an initial run-in phase, where all infants are allocated to NIV-NAVA, and an independent technical committee assesses site performance. Subsequently, all enrolled infants are randomized to NIV-NAVA or NS-NIPPV at extubation. The primary outcome is extubation failure within 5 days of extubation, defined as any of the following: (1) rise in FiO2 at least 20% from pre-extubation for > 2 h, (2) pH ≤ 7.20 or pCO2 ≥ 70 mmHg; (3) > 1 apnea requiring positive pressure ventilation (PPV) or ≥ 6 apneas requiring stimulation within 6 h; (4) emergent intubation for cardiovascular instability or surgery. Our sample size of 478 provides 90% power to detect a 15% absolute reduction in the primary outcome. Enrolled infants will be followed for safety and secondary outcomes through 36 weeks' postmenstrual age, discharge, death, or transfer. DISCUSSION: The DIVA trial is the first large multicenter trial designed to assess the impact of NIV-NAVA on relevant clinical outcomes for preterm infants. The DIVA trial design incorporates input from clinical NAVA experts and includes innovative features, such as a run-in phase, to ensure consistent technical performance across sites. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , trial identifier NCT05446272 , registered July 6, 2022.

Echocardiographic Assessment of Pulmonary Arterial Hypertension Following Inhaled Nitric Oxide in Infants with Severe Bronchopulmonary Dysplasia.

OBJECTIVES: Inhaled nitric oxide (iNO) is an effective pulmonary vasodilator. However, the efficacy of iNO in former premature infants with established bronchopulmonary dysplasia (BPD) has not been studied. This study aimed to determine the efficacy of iNO in reducing pulmonary artery pressure in infants with severe BPD as measured by echocardiography. STUDY DESIGN: Prospective, observational study enrolling infants born at less than 32 weeks gestation and in whom (1) iNO therapy was initiated after admission to our institution, or (2) at the outside institution less than 48 h before transfer and received an echocardiogram prior to iNO initiation, and (3) had severe BPD. Data were collected at three time-points: (1) before iNO; (2) 12-48 h after initiation of iNO; and (3) 48-168 h after initiation of iNO. The primary outcome was the effect of iNO on pulmonary artery pressure measured by echocardiography in patients with severe BPD between 48 and 168 h after initiating iNO therapy. RESULTS: Of 37 enrolled, 81% had echocardiographic evidence of pulmonary arterial hypertension (PAH) before iNO and 56% after 48 h of iNO (p = 0.04). FiO2 requirements were significantly different between time-points (1) and (3) (p = 0.05). There were no significant differences between Tricuspid Annular Plane Systolic Excursion (TAPSE) Z-Scores, time to peak velocity: right ventricular ejection time (TPV:RVET), and ventilator changes. CONCLUSIONS: Although we found a statistically significant reduction of PAH between time-point (1) and (3), future trials are needed to further guide clinical care.

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

Importance: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended. Objective: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants. Design, Setting, and Participants: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022. Exposure: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth. Main Outcomes and Measures: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age. Results: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%). Conclusions and Relevance: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

The Uptake of Telemedicine in Obstetric Care During the Early Acute Phase of the Coronavirus 2019 Pandemic.

Introduction: The early acute phase of the coronavirus disease 2019 pandemic created rapid adaptation in health care delivery. Methods: Using electronic medical record data from two different institutions located in two different states, we examined how telemedicine was integrated into obstetric care. Results: With no telemedicine use prior, both institutions rapidly incorporated telemedicine into prenatal care (PNC). There were significant patient-level and institutional-level differences in telemedicine use. Telemedicine users initiated PNC earlier and had more total visits, earlier timing of ultrasounds, and earlier diabetes screening during pregnancy compared with nonusers. There were no significant differences in delivery mode or stillbirth associated with telemedicine use at either institution. Conclusions: Rapid adoption of obstetric telemedicine maintained adequate prenatal care provision during the early pandemic, but implementation varied across institutions.

Changes in prenatal testing during the COVID-19 pandemic.

Objective: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare delivery, including prenatal care. The study objective was to assess if timing of routine prenatal testing changed during the COVID-19 pandemic. Methods: Retrospective observational cohort study using claims data from a regional insurer (Highmark) and electronic health record data from two academic health systems (Penn Medicine and Yale New Haven) to compare prenatal testing timing in the pre-pandemic (03/10/2018-12/31/2018 and 03/10/2019-12/31/2019) and early COVID-19 pandemic (03/10/2020-12/31/2020) periods. Primary outcomes were second trimester fetal anatomy ultrasounds and gestational diabetes (GDM) testing. A secondary analysis examined first trimester ultrasounds. Results: The three datasets included 31,474 pregnant patients. Mean gestational age for second trimester anatomy ultrasounds increased from the pre-pandemic to COVID-19 period (Highmark 19.4 vs. 19.6 weeks; Penn: 20.1 vs. 20.4 weeks; Yale: 18.8 vs. 19.2 weeks, all p < 0.001). There was a detectable decrease in the proportion of patients who completed the anatomy survey <20 weeks' gestation across datasets, which did not persist at <23 weeks' gestation. There were no consistent changes in timing of GDM screening. There were significant reductions in the proportion of patients with first trimester ultrasounds in the academic institutions (Penn: 57.7% vs. 40.6% and Yale: 78.7% vs. 65.5%, both p < 0.001) but not Highmark. Findings were similar with multivariable adjustment. Conclusion: While some prenatal testing happened later in pregnancy during the pandemic, pregnant patients continued to receive appropriately timed testing. Despite disruptions in care delivery, prenatal screening remained a priority for patients and providers during the COVID-19 pandemic.

Changes in preterm birth during the COVID-19 pandemic by duration of exposure and race and ethnicity.

OBJECTIVE: We aimed to determine whether coronavirus-disease-2019 (COVID-19) pandemic exposure duration was associated with PTB and if the pandemic modified racial disparities. STUDY DESIGN: We analyzed Philadelphia births and replicated in New Haven. Compared to matched months in two prior years, we analyzed overall PTB, specific PTB phenotypes, and stillbirth. RESULTS: Overall, PTB was similar between periods with the following exceptions. Compared to pre-pandemic, early pregnancy (<14 weeks') pandemic exposure was associated with lower risk of PTB < 28 weeks' (aRR 0.60 [0.30-1.10]) and later exposure with higher risk (aRR 1.77 [0.78-3.97]) (interaction p = 0.04). PTB < 32 weeks' among White patients decreased during the pandemic, resulting in non-significant widening of the Black-White disparity from aRR 2.51 (95%CI: 1.53-4.16) to aRR 4.07 (95%CI: 1.56-12.01) (interaction P = 0.41). No findings replicated in New Haven. CONCLUSION: We detected no overall pandemic effects on PTB, but potential indirect benefits for some patients which could widen disparities remains possible.

Neonatal lymphatic flow disorders: central lymphatic flow disorder and isolated chylothorax, diagnosis and treatment using novel lymphatic imaging and interventions technique.

PURPOSE OF REVIEW: Neonatal lymphatic disorders (NLDs) are conditions that are relatively rare and difficult to treat. The recent development of lymphatic imaging, such as Dynamic Contrast-Enhanced MR Lymphangiography and Intranodal Lymphangiography has led to a new, better understanding of the anatomical substrate and pathophysiological mechanisms of the diseases. Consequently, this has allowed the development of new targeted therapeutic interventions as well as prognostication for this population with lymphatic flow disorders. RECENT FINDINGS: The underlying causes of all NLD is an obstruction or altered flow of the central lymphatic flow. Two types of NLD have been described: isolated neonatal chylothorax and central lymphatic flow disorder (CLFD). Isolated neonatal chylothorax can be treated successfully with oil-based contrast (lipiodol) embolization. CLFD secondary to obstruction of the thoraco-venous junction can be successfully treated with surgical thoracic duct-venous anastomosis. CLFD caused by elevated central pressure and/or thoracic duct dysplasia can be treated medically, including with new systemic therapies such as mammalian target of rapamycin inhibitors. SUMMARY: New diagnostic and interventional tools have recently allowed for classification, prognostication, and targeted interventions for neonatal patients with lymphatic flow disorders. Further research will build on these discoveries.

Postpartum Length of Stay and Hospital Readmission Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic.

OBJECTIVE: To compare postpartum hospitalization length of stay (LOS) and hospital readmission among obstetric patients before (March 2017-February 2020; prepandemic) and during the coronavirus disease 2019 (COVID-19) pandemic (March 2020-February 2021). METHODS: We conducted a retrospective cohort study, using Epic Systems' Cosmos research platform, of obstetric patients who delivered between March 1, 2017, and February 28, 2021, at 20-44 weeks of gestation and were discharged within 7 days of delivery. The primary outcome was short postpartum hospitalization LOS (less than two midnights for vaginal births and less than three midnights for cesarean births) and secondary outcome was hospital readmission within 6 weeks of postpartum hospitalization discharge. Analyses compared outcomes before and during the pandemic using standardized differences and Bayesian logistic mixed-effects models, among all births and stratified by mode of delivery. RESULTS: Of the 994,268 obstetric patients in the study cohort, 742,113 (74.6%) delivered prepandemic and 252,155 (25.4%) delivered during the COVID-19 pandemic. During the COVID-19 pandemic, the percentage of short postpartum hospitalizations increased among all births (28.7-44.5%), vaginal births (25.4-39.5%), and cesarean births (35.3-55.1%), which was consistent with the adjusted analysis (all births: adjusted odds ratio [aOR] 2.35, 99% credible interval 2.32-2.39; vaginal births: aOR 2.14, 99% credible interval 2.11-2.18; cesarean births aOR 2.90, 99% credible interval 2.83-2.98). Although short postpartum hospitalizations were more common during the COVID-19 pandemic, there was no change in readmission in the unadjusted (1.4% vs 1.6%, standardized difference=0.009) or adjusted (aOR 1.02, 99% credible interval 0.97-1.08) analyses for all births or when stratified by mode of delivery. CONCLUSION: Short postpartum hospitalization LOS was significantly more common during the COVID-19 pandemic for obstetric patients with no change in hospital readmissions within 6 weeks of postpartum hospitalization discharge. The COVID-19 pandemic created a natural experiment, suggesting shorter postpartum hospitalization may be reasonable for patients who are self-identified or health care professional-identified as appropriate for discharge.

Blanket temperature during therapeutic hypothermia and outcomes in hypoxic ischemic encephalopathy.

OBJECTIVE: Determine whether blanket temperatures during therapeutic hypothermia (TH) are associated with 18-22 month outcomes for infants with hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: Retrospective cohort study of 181 infants with HIE who received TH in two randomized trials within the Neonatal Research Network. We defined summative blanket temperature constructs and evaluated for association with a primary composite outcome of death or moderate/ severe disability at 18-22 months. RESULTS: Each 0.5 °C above 33.5 °C in the mean of the highest quartile blanket temperature was associated with a 52% increase in the adjusted odds of death/ disability (aOR 1.52, 95% CI 1.09-2.11). Having >8 consecutive blanket temperatures above 33.5 °C rendered an aOR of death/disability of 5.04 in the first 24 h (95% CI 1.54-16.6) and 6.92 in the first 48 h (95% CI 2.20-21.8) of TH. CONCLUSIONS: Higher blanket temperature during TH may be an early, clinically useful biomarker of HIE outcome.

A Quality Improvement Initiative to Provide Timely Central Vascular Access in a Neonatal Intensive Care Unit.

BACKGROUND: Timely central venous access is essential in the care of critically ill neonates. Peripherally inserted central catheters (PICCs) are the preferred form of central venous access when umbilical venous catheters cannot be placed or are discontinued. However, time delays increase risk for injury from peripheral intravenous lines and may contribute to inconsistent delivery of necessary fluids and medications. PURPOSE: The aim of this quality improvement project was to decrease wait times for PICC placement in the neonatal intensive care unit (NICU). METHODS: A unit-based PICC team was developed consisting of NICU nurses and attending neonatologists and implemented in 2 phases. Data were collected from chart reviews before, during, and after implementation of the team. We tracked time between PICC order and placement and number of attempts. Hospital metrics on peripheral intravenous line infiltrations and central line-associated blood stream infection were also monitored. At the end of the project, we continued tracking outcomes to determine whether gains would be sustained past the project period. RESULTS: Implementation of a unit-based interdisciplinary specialty team led to a 50% reduction in mean PICC wait times from 1.2 days to 0.58 days. Benefits of the initiative were sustained past the initial project period. IMPLICATIONS FOR PRACTICE: The development of a dedicated, local team played a key role in improving vascular access in the NICU. IMPLICATIONS FOR RESEARCH: Proximity of specialized teams provides a solution to address gaps in care in the NICU.

Birth Hospital Length of Stay and Rehospitalization During COVID-19.

OBJECTIVES: To determine if birth hospitalization length of stay (LOS) and infant rehospitalization changed during the coronavirus disease 2019 (COVID-19) era among healthy, term infants. METHODS: Retrospective cohort study using Epic's Cosmos data from 35 health systems of term infants discharged ≤5 days of birth. Short birth hospitalization LOS (vaginal birth <2 midnights; cesarean birth <3 midnights) and, secondarily, infant rehospitalization ≤7 days after birth hospitalization discharge were compared between the COVID-19 (March 1 to August 31, 2020) and prepandemic eras (March 1 to August 31, 2017, 2018, 2019). Mixed-effects models were used to estimate adjusted odds ratios (aORs) comparing the eras. RESULTS: Among 202 385 infants (57 110 from the COVID-19 era), short birth hospitalization LOS increased from 28.5% to 43.0% for all births (vaginal: 25.6% to 39.3%, cesarean: 40.1% to 61.0%) during the pandemic and persisted after multivariable adjustment (all: aOR 2.30, 95% confidence interval [CI] 2.25-2.36; vaginal: aOR 2.12, 95% CI 2.06-2.18; cesarean: aOR 3.01, 95% CI 2.87-3.15). Despite shorter LOS, infant rehospitalizations decreased slightly during the pandemic (1.2% to 1.1%); results were similar in adjusted analysis (all: aOR 0.83, 95% CI 0.76-0.92; vaginal: aOR 0.82, 95% CI 0.74-0.91; cesarean: aOR 0.87, 95% CI 0.69-1.10). There was no change in the proportion of rehospitalization diagnoses between eras. CONCLUSIONS: Short infant LOS was 51% more common in the COVID-19 era, yet infant rehospitalization within a week did not increase. This natural experiment suggests shorter birth hospitalization LOS among family- and clinician-selected, healthy term infants may be safe with respect to infant rehospitalization, although examination of additional outcomes is needed.

Association Between Increased Seizures During Rewarming After Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy and Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up: A Nested Multisite Cohort Study.

Importance: Compared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce. Objective: To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy. Design, Setting, and Participants: This prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years' follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020. Interventions: Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity. Main Outcomes and Measures: The primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes. Results: A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (κ, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P = .001; group B, 21% vs 10%; P = .03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center. Conclusions and Relevance: Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk. Trial Registration: ClinicalTrials.gov Identifier: NCT01192776.

Coronavirus Disease 2019 (COVID-19) Pandemic and Pregnancy Outcomes in a U.S. Population.

OBJECTIVE: To examine whether the coronavirus disease 2019 (COVID-19) pandemic altered risk of adverse pregnancy-related outcomes and whether there were differences by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status among pregnant women. METHODS: In this retrospective cohort study using Epic's Cosmos research platform, women who delivered during the pandemic (March-December 2020) were compared with those who delivered prepandemic (matched months 2017-2019). Within the pandemic epoch, those who tested positive for SARS-CoV-2 infection were compared with those with negative test results or no SARS-CoV-2 diagnosis. Comparisons were performed using standardized differences, with a value greater than 0.1 indicating meaningful differences between groups. RESULTS: Among 838,489 women (225,225 who delivered during the pandemic), baseline characteristics were similar between epochs. There were no significant differences in adverse pregnancy outcomes between epochs (standardized difference<0.10). In the pandemic epoch, 108,067 (48.0%) women had SARS-CoV-2 testing available; of those, 7,432 (6.9%) had positive test results. Compared with women classified as negative for SARS-CoV-2 infection, those who tested positive for SARS-CoV-2 infection were less likely to be non-Hispanic White or Asian or to reside in the Midwest and more likely to be Hispanic, have public insurance, be obese, and reside in the South or in high social vulnerability ZIP codes. There were no significant differences in the frequency of preterm birth (8.5% vs 7.6%, standardized difference=0.032), stillbirth (0.4% vs 0.4%, standardized difference=-0.002), small for gestational age (6.4% vs 6.5%, standardized difference=-0.002), large for gestational age (7.7% vs 7.7%, standardized difference=-0.001), hypertensive disorders of pregnancy (16.3% vs 15.8%, standardized difference=0.014), placental abruption (0.5% vs 0.4%, standardized difference=0.007), cesarean birth (31.2% vs 29.4%, standardized difference=0.039), or postpartum hemorrhage (3.4% vs 3.1%, standardized difference=0.019) between those who tested positive for SARS-CoV-2 infection and those classified as testing negative. CONCLUSION: In a geographically diverse U.S. cohort, the frequency of adverse pregnancy-related outcomes did not differ between those delivering before compared with during the pandemic, nor between those classified as positive compared with negative for SARS-CoV-2 infection during pregnancy.

Performance Evaluation of Nasal Prong Interface for CPAP Delivery on a Critical Care Ventilator: A Bench Experiment.

BACKGROUND: The RAM cannula (Neotech, Valencia, CA) has become a commonly used interface for CPAP in neonatal intensive care. Performance characteristics of this interface used with a critical care ventilator are not well described. METHODS: This was a bench study utilizing a lung simulator configured as an actively breathing infant (weights of 800 g, 1.5 kg, and 3 kg) with moderate lung disease and a critical care ventilator in CPAP mode with leak compensation on. Three sizes of the RAM cannulae (preemie, newborn, and infant) were compared to 3 BabyFlow nasal prongs (Dräger Medical, Lübeck, Germany) (medium, large, and extra-large). Fabricated nasal models produced a 70% occlusive fit for the RAM cannula and an occlusive fit with the Dräger prongs. Delivered flow and pressure levels were recorded at 9 CPAP levels between 5 and 20 cm H2O. RESULTS: The Dräger prongs produced a mean airway pressure ([Formula: see text]) within 0.20 cm H2O (range -0.10 to 0.35) of the set CPAP across all evaluated prong sizes and CPAP levels. In contrast, the RAM cannula produced [Formula: see text] values that averaged 8.5 cm H2O (range -15 to -3.5) below the set CPAP levels. The deficit in delivered versus target CPAP level for the RAM cannula increased with greater set CPAP. Set CPAP of 5 cm H2O delivered [Formula: see text] values that ranged from 0.6 to 1.5 cm H2O (difference of 3.5-4.4 cm H2O). Set CPAP of 20 cm H2O delivered [Formula: see text] values that ranged from 5.0 to 8.4 cm H2O (difference of 11.7-15 cm H2O). Inspiratory flow required to achieve set CPAP levels did not differ between interfaces, suggesting high resistance in the RAM cannula device masks the delivered CPAP levels. CONCLUSIONS: Use of the RAM cannula with a 30% leak on a critical care ventilator delivered [Formula: see text] values lower than set CPAP. This may be clinically meaningful and should be considered when choosing a nasal interface.

Influence of Patient Characteristics on Antibiotic Use Rates Among Preterm Infants.

BACKGROUND: The antibiotic use rate (AUR) has emerged as a potential metric for neonatal antibiotic use, but reported center-level AURs are limited by differences in case mix. The objective of this study was to identify patient characteristics associated with AUR among a large cohort of preterm infants. METHODS: Retrospective observational study using the Optum Neonatal Database, including infants born from January 1, 2010 through November 30, 2016 with gestational age 23-34 weeks admitted to neonatal units across the United States. Exposures were patient-level characteristics including length of stay, gestational age, sex, race/ethnicity, bacterial sepsis, necrotizing enterocolitis, and survival status. The primary outcome was AUR, defined as days with ≥ 1 systemic antibiotic administered divided by length of stay. Descriptive statistics, univariable comparative analyses, and generalized linear models were utilized. RESULTS: Of 17 910 eligible infants, 17 836 infants (99.6%) from 1090 centers were included. Median gestation was 32.9 (interquartile range [IQR], 30.3-34) weeks. Median length of stay was 25 (IQR, 15-46) days and varied by gestation. Overall median AUR was 0.13 (IQR, 0-0.26) and decreased over time. Gestational age, sex, and race/ethnicity were independently associated with AUR (P < .01). AUR and gestational age had an unexpected inverse parabolic relationship, which persisted when only surviving infants without bacterial sepsis or necrotizing enterocolitis were analyzed. CONCLUSIONS: Neonatal AURs are influenced by patient-level characteristics besides infection and survival status, including gestational age, sex, and race/ethnicity. Neonatal antibiotic use metrics that account for patient-level characteristics as well as morbidity case mix may allow for more accurate comparisons and better inform neonatal antibiotic stewardship efforts.

Tolerability and efficacy of two doses of aerosolized albuterol in ventilated infants with BPD: A randomized controlled crossover trial.

RATIONALE: Aerosolized albuterol is widely used, but its tolerability and efficacy in infants with severe bronchopulmonary dysplasia (sBPD) is not well established. OBJECTIVES: To compare the tolerability and efficacy of two dose levels of aerosolized albuterol to saline placebo in infants with sBPD. METHODS: Single-center, multiple-crossover trial in 24 ventilated very preterm infants with sBPD. Albuterol (1.25 mg, 2.5 mg) and 3 ml of normal saline were administered every 4 h during separate 24-h treatment periods assigned in random order with a 6-h washout phase between periods. The primary outcome was the absolute change (post and pretherapy) in expiratory flow at 75% of exhalation (EF75). Secondary endpoints were changes in ventilator parameters, vital signs, and heart arrhythmia. RESULTS: Average within subject EF75 values improved with each therapy: saline placebo ( + 0.45 L/min ± 2.5, p = .04), 1.25 mg of albuterol ( + 0.70 L/min ± 2.4, p < .001), and 2.5 mg of albuterol ( + 0.38 L/min ± 2.4, p = .06). However, 1.25 mg of albuterol (0.26 L/min; 95% CI -0.19, 0.72) and 2.5 mg (-0.10 L/min; 95% CI -0.77, 0.57) produced similar changes in EF75 when compared to saline. All secondary outcomes were similar between saline and 1.25 mg of albuterol. Peak inspiratory pressure needed to deliver goal tidal volumes (7.5% relative decrease, 95% CI 2.6, 12.3) and heart rate (6.5% increase, 95% CI 2.2, 10.8) differed significantly between albuterol 2.5 mg and saline. CONCLUSION: Albuterol at 1.25 mg and 2.5 mg, compared to aerosolized saline, did not affect EF75 in infants with sBPD receiving invasive ventilation. Greater improvement in peak inspiratory pressures with albuterol 2.5 mg suggests benefit, but close heart monitoring may be indicated.