Mihoko V. Bennett

Neonatal Intensive Care Unit Antibiotic Use

BACKGROUND AND OBJECTIVES: Treatment of suspected infection is a mainstay of the daily work in the NICU. We hypothesized that NICU antibiotic prescribing practice variation correlates with rates of proven infection, necrotizing enterocolitis (NEC), mortality, inborn admission, and with NICU surgical volume and average length of stay. METHODS: In a retrospective cohort study of 52 061 infants in 127 NICUs across California during 2013, we compared sample means and explored linear and nonparametric correlations, stratified by NICU level of care and lowest/highest antibiotic use rate quartiles. RESULTS: Overall antibiotic use varied 40-fold, from 2.4% to 97.1% of patient-days; median = 24.5%. At all levels of care, it was independent of proven infection, NEC, surgical volume, or mortality. Fifty percent of intermediate level NICUs were in the highest antibiotic use quartile, yet most of these units reported infection rates of zero. Regional NICUs in the highest antibiotic quartile reported inborn admission rate 218% higher (0.24 vs 0.11, P = .03), and length of stay 35% longer (90.2 days vs 66.9 days, P = .03) than regional NICUs in the lowest quartile. CONCLUSIONS: Forty-fold variation in NICU antibiotic prescribing practice across 127 NICUs with similar burdens of proven infection, NEC, surgical volume, and mortality indicates that a considerable portion of antibiotic use lacks clear warrant; in some NICUs, antibiotics are overused. Additional study is needed to establish appropriate use ranges and elucidate the determinants and directionality of relationships between antibiotic and other resource use.

Implementation Methods for Delivery Room Management: A Quality Improvement Comparison Study

BACKGROUND: There is little evidence to compare the effectiveness of large collaborative quality improvement versus individual local projects. METHODS: This was a prospective pre-post intervention study of neonatal resuscitation practice, comparing 3 groups of nonrandomized hospitals in the California Perinatal Quality Care Collaborative: (1) collaborative, hospitals working together through face-to-face meetings, webcasts, electronic mailing list, and data sharing; (2) individual, hospitals working independently; and (3) nonparticipant hospitals. The collaborative and individual arms participated in improvement activities, focusing on reducing hypothermia and invasive ventilatory support. RESULTS: There were 20 collaborative, 31 individual, and 44 nonparticipant hospitals caring for 12 528 eligible infants. Each group had reduced hypothermia from baseline to postintervention. The collaborative group had the most significant decrease in hypothermia, from 39% to 21%, compared with individual hospital efforts of 38% to 33%, and nonparticipants of 42% to 34%. After risk adjustment, the collaborative group had twice the magnitude of decrease in rates of newborns with hypothermia compared with the other groups. Collaborative improvement also led to greater decreases in delivery room intubation (53% to 40%) and surfactant administration (37% to 20%). CONCLUSIONS: Collaborative efforts resulted in larger improvements in delivery room outcomes and processes than individual efforts or nonparticipation. These findings have implications for planning quality improvement projects for implementation of evidence-based practices.

A Randomized Clinical Trial of Therapeutic Hypothermia Mode during Transport for Neonatal Encephalopathy

OBJECTIVE To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice. STUDY DESIGN We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation. RESULTS One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001). CONCLUSIONS Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.

Accounting for variation in length of NICU stay for extremely low birth weight infants

Objective:To develop a length of stay (LOS) model for extremely low birth weight (ELBW) infants.Study Design:We included infants from the California Perinatal Quality Care Collaborative with birth weight 401 to 1000 g who were discharged to home. Exclusion criteria were congenital anomalies, surgery and death. LOS was defined as days from admission to discharge. As patients who died or were transferred to lower level of care were excluded, we assessed correlation of hospital mortality rates and transfers to risk-adjusted LOS.Results:There were 2012 infants with median LOS 79 days (range 23 to 219). Lower birth weight, lack of antenatal steroids and lower Apgar score were associated with longer LOS. There was negligible correlation between risk-adjusted LOS and hospital mortality rates (r=0.0207) and transfer-out rates (r=0.121).Conclusion:Particularly because ELBW infants have extended hospital stays, identification of unbiased and informative risk-adjusted LOS for these infants is an important step in benchmarking best practice and improving efficiency in care.

Dual Manganese-Enhanced and Delayed Gadolinium-Enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia- Reperfusion Model

Background— Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn2+)-enhanced MRI (MEMRI) denotes specific Mn2+ uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo. Methods and Results— Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn2+ contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75; P<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6; P>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement. Conclusions— The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.

The Association of Level of Care With NICU Quality.

BACKGROUND: Regionalized care delivery purportedly optimizes care to vulnerable very low birth weight (VLBW; <1500 g) infants. However, a comprehensive assessment of quality of care delivery across different levels of NICUs has not been done. METHODS: We conducted a cross-sectional analysis of 21 051 VLBW infants in 134 California NICUs. NICUs designated their level of care according to 2012 American Academy of Pediatrics guidelines. We assessed quality of care delivery via the Baby-MONITOR, a composite indicator, which combines 9 risk-adjusted measures of quality. Baby-MONITOR scores are measured as observed minus expected performance, expressed in standard units with a mean of 0 and an SD of 1. RESULTS: Wide variation in Baby-MONITOR scores exists across California (mean [SD] 0.18 (1.14), range –2.26 to 3.39). However, level of care was not associated with overall quality scores. Subcomponent analysis revealed trends for higher performance of Level IV NICUs on several process measures, including antenatal steroids and any human milk feeding at discharge, but lower scores for several outcomes including any health care associated infection, pneumothorax, and growth velocity. No other health system or organizational factors including hospital ownership, neonatologist coverage, urban or rural location, and hospital teaching status, were significantly associated with Baby-MONITOR scores. CONCLUSIONS: The comprehensive assessment of the effect of level of care on quality reveals differential opportunities for improvement and allows monitoring of efforts to ensure that fragile VLBW infants receive care in appropriate facilities.

Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured MyocardiumNovelty and Significance

Rationale: Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear. Objective: To evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model. Methods and Results: Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups. Conclusions: This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through their differential paracrine effects.

Effects of delivery room quality improvement on premature infant outcomes.

Objective:Delivery room management interventions have been successfully implemented via collaborative quality improvement (QI) projects. However, it is unknown whether these successes translate to reductions in neonatal morbidity and mortality.Study Design:This was a prospective pre–post intervention study of three nonrandomized hospital groups within the California Perinatal Quality Care Collaborative. A collaborative QI model (Collaborative QI) was compared with a single-site QI model (NICU QI) and a non-participant population when implementing evidence-based delivery room practices. The intervention period was between June 2011 and May 2012. Infants born with gestational age between 22 weeks 0 days and 29 weeks 6 days and birth weight ⩽1500 g were included. Outcomes were mortality and select morbidities (bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC)). Outcomes were compared between the baseline (January 2010 to May 2011) and post-intervention period (June 2012 to May 2013) within each comparison group.Results:Ninety-five hospitals were included with 4222 infants in the baseline period and 4186 infants in the post-intervention period. The Collaborative QI group had significantly reduced odds of developing BPD post-intervention (odds ratio (OR) 0.8, 95% confidence interval (CI) 0.65 to 0.99) or composite BPD-death (OR 0.83, 95% CI 0.69 to 1.00). In both the Collaborative QI and non-participants there were also reductions in IVH, severe IVH, composite severe IVH-death, severe ROP and composite severe ROP-death.Conclusion:Hospitals dedicated to improving delivery room practices can impact neonatal outcomes.

Racial/Ethnic Disparity in NICU Quality of Care Delivery

By using the Baby-MONITOR, a composite indicator of NICU quality, the authors of this study examined racial and/or ethnic disparities. BACKGROUND: Differences in NICU quality of care provided to very low birth weight (<1500 g) infants may contribute to the persistence of racial and/or ethnic disparity. An examination of such disparities in a population-based sample across multiple dimensions of care and outcomes is lacking. METHODS: Prospective observational analysis of 18 616 very low birth weight infants in 134 California NICUs between January 1, 2010, and December 31, 2014. We assessed quality of care via the Baby-MONITOR, a composite indicator consisting of 9 process and outcome measures of quality. For each NICU, we calculated a risk-adjusted composite and individual component quality score for each race and/or ethnicity. We standardized each score to the overall population to compare quality of care between and within NICUs. RESULTS: We found clinically and statistically significant racial and/or ethnic variation in quality of care between NICUs as well as within NICUs. Composite quality scores ranged by 5.26 standard units (range: −2.30 to 2.96). Adjustment of Baby-MONITOR scores by race and/or ethnicity had only minimal effect on comparative assessments of NICU performance. Among subcomponents of the Baby-MONITOR, non-Hispanic white infants scored higher on measures of process compared with African Americans and Hispanics. Compared with whites, African Americans scored higher on measures of outcome; Hispanics scored lower on 7 of the 9 Baby-MONITOR subcomponents. CONCLUSIONS: Significant racial and/or ethnic variation in quality of care exists between and within NICUs. Providing feedback of disparity scores to NICUs could serve as an important starting point for promoting improvement and reducing disparities.

Cytomegalovirus infection among infants in California neonatal intensive care units, 2005–2010

Abstract Aim: To assess the burden of congenital and perinatal cytomegalovirus (CMV) disease among infants hospitalized in neonatal intensive care units (NICUs). Methods: CMV infection was defined as a report of positive CMV viral culture or polymerase chain reaction at any time since birth in an infant hospitalized in a NICU reporting to California Perinatal Quality Care Collaborative during 2005–2010. Results: One hundred and fifty-six (1.7 per 1000) infants were reported with CMV infection, representing an estimated 5% of the expected number of live births with symptomatic CMV disease. Prevalence was higher among infants with younger gestational ages and lower birth weights. Infants with CMV infection had significantly longer hospital stays and 14 (9%) died. Conclusions: Reported prevalence of CMV infection in NICUs represents a fraction of total expected disease burden from CMV in the newborn period, likely resulting from underdiagnosis and milder symptomatic cases that do not require NICU care. More complete ascertainment of infants with congenital CMV infection that would benefit from antiviral treatment may reduce the burden of CMV disease in this population.