Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature.

BACKGROUND AND OBJECTIVES: Extremely low gestational age neonates born <28 weeks gestation are at risk for chronic disease. We sought to describe the prevalence of kidney outcomes by gestational age and determine risk factors for their development. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) study examined kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo NeuroProtection Trial (PENUT) study. Kidney function, urine albumin, and BP were measured at 2-year (24±2 months) corrected gestational age. We compared outcomes across gestational age categories and evaluated associations between kidney-related outcomes and neonatal and maternal characteristics. The primary outcome was eGFR <90 ml/min per 1.73 m2 (CKD); secondary outcomes were spot urine albumin-creatinine ratio ≥30 mg/g (albuminuria) and either systolic BP or diastolic BP >90th percentile for height, age, and sex. RESULTS: A total of 832 survived to 2 years, and 565 (68%) had at least one outcome measured. Overall, 297 (53%) had one abnormal kidney outcome; 61 (18%) had an eGFR <90 ml/min per 1.73 m2, 155 (36%) had albuminuria, 65 (22%) had elevated systolic BP, and 128 (44%) had elevated diastolic BP. Gestational age (odds ratio, 0.94; 95% confidence interval, 0.89 to 0.99), birth weight z-score (odds ratio, 0.92; 95% confidence interval, 0.85 to 0.98), and prenatal steroids (odds ratio, 1.23; 95% confidence interval, 1.08 to 1.39) were associated with an eGFR <90 ml/min per 1.73 m2. An elevated systolic BP was associated with indomethacin use (odds ratio, 1.18; 95% confidence interval, 1.04 to 1.33) and Black race (odds ratio, 1.19; 95% confidence interval, 1.01 to 1.39); elevated diastolic BP was associated with male sex (odds ratio, 1.29; 95% confidence interval, 1.12 to 1.49), severe AKI (odds ratio, 1.24; 95% confidence interval, 1.04 to 1.48), and indomethacin use (odds ratio, 1.16; 95% confidence interval, 1.01 to 1.33). CONCLUSIONS: Approximately 18% of extremely low gestational age neonates have CKD, 36% have albuminuria, 22% have an elevated systolic BP, and 44% have an elevated diastolic BP at 2 years of age. Gestational age, birthweight z-score, and prenatal steroids were associated with CKD. Male sex, Black race, indomethacin use, and severe AKI were associated with elevated BP. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_19_CJN15011121.mp3.

Coronavirus Disease 2019 in Pregnancy and Outcomes Among Pregnant Women and Neonates: A Literature Review.

Limited data are available about the outcomes of coronavirus disease 2019 (COVID-19) during pregnancy and risk of vertical transmission in exposed neonates. We reviewed studies published February 1, 2020, through August 15, 2020, on outcomes in pregnant women with COVID-19 and neonates with perinatal exposure. Among pregnant women with COVID-19, 181 (11%) required intensive care unit admission and 123 (8%) required mechanical ventilation. There were 22 maternal deaths. Most infections occurred in the third trimester. Among women who delivered, 28% had a preterm birth, and 57% had a Caesarean section. Sixty-one (4%) of 1222 neonates with reported testing had at least 1 positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. The most common symptom among neonates was respiratory distress (n = 126; 21%). There were 14 neonatal deaths, one of which occurred in a neonate with positive testing. Further study of COVID-19 in pregnant women and neonates, including standardized reporting of outcomes, testing and treatment protocols, is essential to optimize maternal and neonatal care.

Community-Onset Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Young Infants: A Systematic Review.

OBJECTIVE: To summarize and evaluate current reports on community-onset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young infants. STUDY DESIGN: We performed a systematic review to identify reports published from November 1, 2019, until June 15, 2020, on laboratory-confirmed community-onset SARS-CoV-2 infection in infants younger than 3 months of age. We excluded studies reporting neonates with perinatal coronavirus disease 2019 (COVID-19) exposure and diagnosis before hospital discharge and hospital-onset disease, as well as clinically diagnosed cases without confirmation. Two independent reviewers performed study screening, data abstraction, and risk of bias assessment. Variables of interest included patient age, exposure to COVID-19, medical history, clinical symptoms, SARS-CoV-2 testing, laboratory findings, clinical course, and disposition. RESULTS: In total, 38 publications met inclusion criteria, including 23 single case reports, 14 case series, and 1 cohort study, describing 63 infants younger than 3 months of age with laboratory-confirmed SARS-CoV-2 infection. Most cases were mild to moderate. Fever, respiratory, gastrointestinal, cardiac, and neurologic findings were reported. Laboratory abnormalities included neutropenia, lymphopenia, and elevated serum levels of inflammatory markers and aminotransferases. Fifty-eight (92%) infants were hospitalized, 13 (21%) were admitted to the intensive care unit, and 2 (3%) required mechanical ventilation. No death was reported. CONCLUSIONS: Among young infants with laboratory-confirmed SARS-CoV-2 infection, most cases were mild to moderate and improved with supportive care. Our results demonstrate a need for a high index of suspicion for SARS-CoV-2 infection in young infants presenting with generalized symptoms such as fever or decreased feeding, even in the absence of respiratory symptoms.

Later cooling within 6 h and temperatures outside 33-34 °C are not associated with dysfunctional autoregulation during hypothermia for neonatal encephalopathy.

BACKGROUND: Cooling delays, temperature outside 33-34 °C, and blood pressure below the mean arterial blood pressure with optimal cerebral autoregulation (MAPOPT) might diminish neuroprotection from therapeutic hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized that longer time to reach temperature <34 °C and having temperature outside 33-34 °C would be associated with worse autoregulation and greater brain injury. METHODS: Neonates with HIE had rectal temperature and near-infrared spectroscopy autoregulation monitoring during hypothermia (n = 63) and rewarming (n = 58). All underwent brain MRI, and a subset received diffusion tensor imaging MRI before day 10 (n = 41). RESULTS: Most neonates reached <34 °C at 3-6 h of life. MAPOPT was identified in 54/63 (86%) during hypothermia and in 53/58 (91%) during rewarming. Cooling time was not related to blood pressure deviation from MAPOPT. Later cooling was associated with lower ADC scalar in unilateral posterior centrum semiovale but not in other regions. Temperatures >34 °C were associated with blood pressure above MAPOPT but not with brain injury. CONCLUSIONS: In neonates who were predominantly cooled after 3 h, cooling time was not associated with autoregulation or overall brain injury. Blood pressure deviation above MAPOPT was associated with temperature >34 °C. Additional studies are needed in a more heterogeneous population. IMPACT: Cooling time to reach target hypothermia temperature within 6 h of birth did not affect cerebral autoregulation measured by NIRS in neonates with hypoxic-ischemic encephalopathy (HIE). Temperature fluctuations >33-34 °C were associated with blood pressures that exceeded the range of optimal autoregulatory vasoreactivity. Cooling time within 6 h of birth and temperatures >33-34 °C were not associated with qualitative brain injury on MRI. Regional apparent diffusion coefficient scalars on diffusion tensor imaging MRI were not appreciably affected by cooling time or temperature >33-34 °C. Additional research in a larger and more heterogeneous population is needed to determine how delayed cooling and temperatures beyond the target hypothermia range affect autoregulation and brain injury.

Effect of High-Dose Erythropoietin on Blood Transfusions in Extremely Low Gestational Age Neonates: Post Hoc Analysis of a Randomized Clinical Trial.

Importance: Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure. Objectives: To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions. Design, Setting, and Participants: The Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464). Data were collected from December 12, 2013, to February 25, 2019, and analyzed from March 1 to June 15, 2019. Interventions: In this post hoc analysis, erythropoietin, 1000 U/kg, or placebo was given every 48 hours for 6 doses, followed by 400 U/kg or sham injections 3 times a week through postmenstrual age of 32 weeks. Main Outcomes and Measures: Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein. Results: A total of 936 patients (488 male [52.1%]) were included in the analysis, with a mean (SD) gestational age of 25.6 (1.2) weeks and mean (SD) birth weight of 799 (189) g. Erythropoietin treatment (vs placebo) decreased the number of transfusions (unadjusted mean [SD], 3.5 [4.0] vs 5.2 [4.4]), with a relative rate (RR) of 0.66 (95% CI, 0.59-0.75); the cumulative transfused volume (mean [SD], 47.6 [60.4] vs 76.3 [68.2] mL), with a mean difference of -25.7 (95% CI, 18.1-33.3) mL; and donor exposure (mean [SD], 1.6 [1.7] vs 2.4 [2.0]), with an RR of 0.67 (95% CI, 0.58-0.77). Despite fewer transfusions, erythropoietin-treated infants tended to have higher hematocrit levels than placebo-treated infants, most noticeable at gestational week 33 in infants with a gestational age of 27 weeks (mean [SD] hematocrit level in erythropoietin-treated vs placebo-treated cohorts, 36.9% [5.5%] vs 30.4% [4.6%] (P < .001). Of 936 infants, 160 (17.1%) remained transfusion free at the end of 12 postnatal weeks, including 43 in the placebo group and 117 in the erythropoietin group (P < .001). Conclusions and Relevance: These findings suggest that high-dose erythropoietin as used in the PENUT protocol was effective in reducing transfusion needs in this population of extremely preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.

A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.

BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. METHODS: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events. CONCLUSIONS: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).

Effect of Treating Parents Colonized With Staphylococcus aureus on Transmission to Neonates in the Intensive Care Unit: A Randomized Clinical Trial.

Importance: Staphylococcus aureus is a leading cause of health care-associated infections in the neonatal intensive care unit (NICU). Parents may expose neonates to S aureus colonization, a well-established predisposing factor to invasive S aureus disease. Objective: To test whether treating parents with intranasal mupirocin and topical chlorhexidine compared with placebo would reduce transmission of S aureus from parents to neonates. Design, Setting, and Participants: Double-blinded randomized clinical trial in 2 tertiary NICUs in Baltimore, Maryland. Neonates (n = 236) with S aureus-colonized parent(s) were enrolled. The study period was November 7, 2014, through December 13, 2018. Interventions: Parents were assigned to intranasal mupirocin and 2% chlorhexidine-impregnated cloths (active treatment, n = 117) or petrolatum intranasal ointment and nonmedicated soap cloths (placebo, n = 119) for 5 days. Main Outcomes and Measures: The primary end point was concordant S aureus colonization by 90 days, defined as neonatal acquisition of an S aureus strain that was the same strain as a parental strain at time of screening. Secondary outcomes included neonatal acquisition of any S aureus strain and neonatal S aureus infections. Results: Among 236 randomized neonates, 208 were included in the analytic sample (55% male; 76% singleton births; mean birth weight, 1985 g [SD, 958 g]; 76% vaginal birth; mean parent age, 31 [SD, 7] years), of whom 18 were lost to follow-up. Among 190 neonates included in the analysis, 74 (38.9%) acquired S aureus colonization by 90 days, of which 42 (56.8%) had a strain concordant with a parental baseline strain. In the intervention and placebo groups, 13 of 89 neonates (14.6%) and 29 of 101 neonates (28.7%), respectively, acquired concordant S aureus colonization (risk difference, -14.1% [95% CI, -30.8% to -3.9%]; hazard ratio [HR], 0.43 [95.2% CI, 0.16 to 0.79]). A total of 28 of 89 neonates (31.4%) in the intervention group and 46 of 101 (45.5%) in the control group acquired any S aureus strain (HR, 0.57 [95% CI, 0.31 to 0.88]), and 1 neonate (1.1%) in the intervention group and 1 neonate (1.0%) in the control group developed an S aureus infection before colonization. Skin reactions in parents were common (4.8% intervention, 6.2% placebo). Conclusions and Relevance: In this preliminary trial of parents colonized with S aureus, treatment with intranasal mupirocin and chlorhexidine-impregnated cloths compared with placebo significantly reduced neonatal colonization with an S aureus strain concordant with a parental baseline strain. However, further research is needed to replicate these findings and to assess their generalizability. Trial Registration: ClinicalTrials.gov Identifier: NCT02223520.

Severe Neonatal Manifestations of Infantile Liver Failure Syndrome Type 1 Caused by Cytosolic Leucine-tRNA Synthetase Deficiency.

BACKGROUND: Deleterious mutations in cytosolic leucine-tRNA synthetase (LARS) cause infantile liver failure syndrome, type 1 (ILFS1), a recently recognized, rare autosomal recessive disorder (OMIM151350). Only six families with ILFS1 have been reported in the literature. Patients with ILFS1 are typically diagnosed between 5 and 24 months of age with failure to thrive, developmental delays, encephalopathy, microcytic anemia, and chronic liver dysfunction with recurrent exacerbations following childhood illnesses. Neonatal manifestations of this disorder have not been well documented. CASE REPORT: We report a premature female newborn with intrauterine growth restriction, failure to thrive, congenital anemia, anasarca, and fulminant liver failure leading to lethal multiple organ failure. Liver failure in this infant was characterized by a disproportionate impairment of liver synthetic function, including severe coagulopathy and hypoalbuminemia without significant defects in liver detoxification or evidence of hepatocellular injury during early phase of the disease. Whole-exome sequencing of child-parent trio identified two inherited missense mutations in LARS in this patient. One, c.1292T>A; p.Val431Asp, has been reported in patients with ILFS1, while the other, c.725C>T; p.Pro242Leu, is novel. Both mutations involve amino acid residues in the highly conserved editing domain of LARS, are predicted to be functionally deleterious, and presumably contribute to the clinical manifestations in this patient. CONCLUSION: This is the first case documenting neonatal manifestation of ILFS1, highlighting early, severe, and disproportionate defects in liver synthetic function. Timely diagnosis of ILFS1 is crucial to guide critical clinical management and improve outcomes of this rare and potentially life-threatening disorder.

Cerebral Autoregulation and Conventional and Diffusion Tensor Imaging Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Deviation of mean arterial blood pressure (MAP) from the range that optimizes cerebral autoregulatory vasoreactivity (optimal MAP) could increase neurological injury from hypoxic-ischemic encephalopathy (HIE). We tested whether a global magnetic resonance imaging (MRI) brain injury score and regional diffusion tensor imaging (DTI) are associated with optimal MAP in neonates with HIE. METHODS: Twenty-five neonates cooled for HIE were monitored with the hemoglobin volume index. In this observational study, we identified optimal MAP and measured brain injury by qualitative and quantitative MRIs with the Neonatal Research Network (NRN) score and DTI mean diffusivity scalars. Optimal MAP and blood pressure were compared with brain injury. RESULTS: Neonates with blood pressure measurements within optimal MAP during rewarming had less brain injury by NRN score (P = 0.040). Longer duration of MAP within optimal MAP during hypothermia correlated with higher mean diffusivity in the anterior centrum semiovale (P = 0.008) and pons (P = 0.002). Blood pressure deviation below optimal MAP was associated with lower mean diffusivity in cerebellar white matter (P = 0.033). Higher optimal MAP values related to lower mean diffusivity in the basal ganglia (P = 0.021), the thalamus (P = 0.006), the posterior limb of the internal capsule (P = 0.018), the posterior centrum semiovale (P = 0.035), and the cerebellar white matter (P = 0.008). Optimal MAP values were not associated with the NRN score. CONCLUSIONS: The NRN score and the regional mean diffusivity scalars detected injury with mean arterial blood pressure deviations from the optimal MAP. Higher optimal MAP and lower mean diffusivity may be related because of cytotoxic edema and limited vasodilatory reserve at low MAP in injured brain. DTI detected injury with elevated optimal MAP better than the NRN score.

Sex-specific associations between cerebrovascular blood pressure autoregulation and cardiopulmonary injury in neonatal encephalopathy and therapeutic hypothermia.

BACKGROUND: Cardiopulmonary injury is common in neonatal encephalopathy, but the link with cerebrovascular dysfunction is unknown. We hypothesized that alterations of cerebral autoregulation are associated with cardiopulmonary injury in neonates treated with therapeutic hypothermia (TH) for neonatal encephalopathy. METHODS: The cerebral hemoglobin volume index (HVx) from near-infrared spectroscopy was used to identify the mean arterial blood pressure (MAP) with optimal autoregulatory vasoreactivity (MAPOPT). We measured associations between MAP relative to MAPOPT and indicators of cardiopulmonary injury (duration of mechanical respiratory support and administration of inhaled nitric oxide (iNO), milrinone, or steroids). RESULTS: We identified associations between cerebrovascular autoregulation and cardiopulmonary injury that were often sex-specific. Greater MAP deviation above MAPOPT was associated with shorter duration of intubation in boys but longer ventilatory support in girls. Greater MAP deviation below MAPOPT related to longer intensive care stay in boys. Milrinone was associated with greater MAP deviation below MAPOPT in girls. CONCLUSION: MAP deviation from MAPOPT may relate to cardiopulmonary injury after neonatal encephalopathy, and sex may modulate this relationship. Whereas MAP above MAPOPT may protect the brain and lungs in boys, it may be related to cardiopulmonary injury in girls. Future studies are needed to characterize the role of sex in these associations.

Optimizing Cerebral Autoregulation May Decrease Neonatal Regional Hypoxic-Ischemic Brain Injury.

BACKGROUND: Therapeutic hypothermia provides incomplete neuroprotection for neonatal hypoxic-ischemic encephalopathy (HIE). We examined whether hemodynamic goals that support autoregulation are associated with decreased brain injury and whether these relationships are affected by birth asphyxia or vary by anatomic region. METHODS: Neonates cooled for HIE received near-infrared spectroscopy autoregulation monitoring to identify the mean arterial blood pressure with optimized autoregulatory function (MAPOPT). Blood pressure deviation from MAPOPT was correlated with brain injury on MRI after adjusting for the effects of arterial carbon dioxide, vasopressors, seizures, and birth asphyxia severity. RESULTS: Blood pressure deviation from MAPOPT related to neurologic injury in several regions independent of birth asphyxia severity. Greater duration and deviation of blood pressure below MAPOPT were associated with greater injury in the paracentral gyri and white matter. Blood pressure within MAPOPT related to lesser injury in the white matter, putamen and globus pallidus, and brain stem. Finally, blood pressures that exceeded MAPOPT were associated with reduced injury in the paracentral gyri. CONCLUSIONS: Blood pressure deviation from optimal autoregulatory vasoreactivity was associated with MRI markers of brain injury that, in many regions, were independent of the initial birth asphyxia. Targeting hemodynamic ranges to optimize autoregulation has potential as an adjunctive therapy to hypothermia for HIE.

Treating Parents to Reduce NICU Transmission of Staphylococcus aureus (TREAT PARENTS) trial: protocol of a multisite randomised, double-blind, placebo-controlled trial.

INTRODUCTION: More than 33,000 healthcare-associated infections occur in neonatal intensive care units (NICUs) each year in the USA. Parents, rather than healthcare workers, may be a reservoir from which neonates acquire Staphylococcus aureus (S. aureus) colonisation in the NICU. This study looks to measure the effect of treating parents with short course intranasal mupirocin and topical chlorhexidine antisepsis on acquisition of S. aureus colonisation and infection in neonates. METHODS AND ANALYSIS: The TREAT PARENTS trial (Treating Parents to Reduce Neonatal Transmission of S. aureus) is a multicentre randomised, masked, placebo-controlled trial. Shortly after a neonate is admitted to the NICU, parents will be tested for S. aureus colonisation. If either parent screens positive for S. aureus, then both parents as a pair will be enrolled and randomised to one of the two possible masked treatment arms. Arm 1 will include assignment to intranasal 2% mupirocin plus topical antisepsis with chlorhexidine gluconate impregnated cloths for 5 days. Arm 2 will include assignment to placebo ointment and placebo cloths for skin antisepsis for 5 days. The primary outcome will be neonatal acquisition of an S. aureus strain that is concordant to the parental baseline S. aureus strain as determined by periodic surveillance cultures or a culture collected during routine clinical care that grows S. aureus. Secondary outcomes will include neonatal acquisition of S. aureus, neonatal S. aureus infection, eradication of S. aureus colonisation in parents, natural history of S. aureus colonisation in parents receiving placebo, adverse reactions to treatment, feasibility of intervention, and attitudes and behaviour in consented parents. Four hundred neonate-parent pairs will be enrolled. ETHICS AND DISSEMINATION: The study was approved by Johns Hopkins University IRB in June 2014 (IRB number 00092982). Protocol V.7 was approved in November 2014. Findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02223520.

Clinical Communities at Johns Hopkins Medicine: An Emerging Approach to Quality Improvement.

BACKGROUND: Clinical communities are an emerging approach to quality improvement (QI) to which several large-scale projects have attributed some success. In 2011 the Armstrong Institute for Patient Safety and Quality established clinical communities as a core strategy to connect frontline providers from six different hospitals to improve quality of care, patient safety, and value across the health system. CLINICAL COMMUNITIES: Fourteen clinical communities that presented great opportunity for improvement were established. A community could focus on a clinical area, a patient population, a group, a process, a safety-related issue, or nearly any health care issue. The collaborative spirit of the communities embraced interdisciplinary membership and representation from each hospital in each community. Communities engaged in team-building activities and facilitated discussions, met monthly, and were encouraged to meet in person to develop relationships and build trust. After a community was established, patients and families were invited to join and share their perspectives and experiences. ENABLING STRUCTURES: The clinical community structure provided clinicians access to resources, such as technical experts and safety and QI researchers, that were not easily otherwise accessible or available. Communities convened clinicians from each hospital to consider safety problems and their resolution and share learning with workplace peers and local unit safety teams. CONCLUSION: The clinical communities engaged 195 clinicians from across the health system in QI projects and peer learning. Challenges included limited financial support and time for clinicians, timely access to data, limited resources from the health system, and not enough time with improvement experts.

Cerebrovascular autoregulation and neurologic injury in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Neonates with hypoxic-ischemic encephalopathy (HIE) are at risk of cerebral blood flow dysregulation. Our objective was to describe the relationship between autoregulation and neurologic injury in HIE. METHODS: Neonates with HIE had autoregulation monitoring with the hemoglobin volume index (HVx) during therapeutic hypothermia, rewarming, and the first 6 h of normothermia. The 5-mm Hg range of mean arterial blood pressure (MAP) with best vasoreactivity (MAPOPT) was identified. The percentage of time spent with MAP below MAPOPT and deviation in MAP from MAPOPT were measured. Neonates received brain magnetic resonance imaging (MRI) 3-7 d after treatment. MRIs were coded as no, mild, or moderate/severe injury in five regions. RESULTS: HVx identified MAPOPT in 79% (19/24), 77% (17/22), and 86% (18/21) of the neonates during hypothermia, rewarming, and normothermia, respectively. Neonates with moderate/severe injury in paracentral gyri, white matter, basal ganglia, and thalamus spent a greater proportion of time with MAP below MAPOPT during rewarming than neonates with no or mild injury. Neonates with moderate/severe injury in paracentral gyri, basal ganglia, and thalamus had greater MAP deviation below MAPOPT during rewarming than neonates without injury. CONCLUSION: Maintaining MAP within or above MAPOPT may reduce the risk of neurologic injuries in neonatal HIE.

Evaluating information prescriptions in two clinical environments.

OBJECTIVE: The research sought to evaluate whether providing personalized information services by libraries can improve satisfaction with information services for specific types of patients. METHODS: Adult breast cancer (BrCa) clinic patients and mothers of inpatient neonatal intensive care unit (NICU) patients were randomized to receive routine information services (control) or an IRx intervention. RESULTS: The BrCa trial randomized 211 patients and the NICU trial, 88 mothers. The BrCa trial showed no statistically significant differences in satisfaction ratings between the treatment and control groups. The IRx group in the NICU trial reported higher satisfaction than the control group regarding information received about diagnosis, treatments, respiratory tradeoffs, and medication tradeoffs. BrCa patients posed questions to librarians more frequently than did NICU mothers, and a higher percentage reported using the website. Questions asked of the librarians by BrCa patients were predominantly clinical and focused on the areas of treatment and side effects. CONCLUSIONS: Study results provide some evidence to support further efforts to both implement information prescription projects in selected settings and to conduct additional research on the costs and benefits of services.

Inhaled nitric oxide in preterm infants: a systematic review.

CONTEXT: Studies of the efficacy of inhaled nitric oxide (iNO) to prevent or treat respiratory failure in preterm infants have had variable and contradictory findings. OBJECTIVES: To systematically review the evidence on the use of iNO in infants born at ≤ 34 weeks' gestation who receive respiratory support. METHODS: Medline, Embase, the Cochrane Central Register of Controlled Studies, PsycInfo, ClinicalTrials.gov, and proceedings of the 2009 and 2010 Pediatric Academic Societies meetings were searched in June 2010. Additional studies from reference lists of eligible articles, relevant reviews, and technical experts were considered. Two investigators independently screened search results and abstracted data from eligible articles. We focus here on mortality, bronchopulmonary dysplasia (BPD), the composite outcome of death or BPD, and neurodevelopmental impairment. RESULTS: Fourteen randomized controlled trials, 7 follow-up studies, and 1 observational study were eligible for inclusion. Mortality rates in the NICU did not differ for infants treated with iNO compared with controls (risk ratio [RR]: 0.97 [95% confidence interval (CI): 0.82-1.15]). BPD at 36 weeks for iNO and control groups also did not differ for survivors (RR: 0.93 [95% CI: 0.86-1.003]). A small difference was found in favor of iNO in the composite outcome of death or BPD (RR: 0.93 [95% CI: 0.87-0.99]). There was no evidence to suggest a difference in the incidence of cerebral palsy (RR: 1.36 [95% CI: 0.88-2.10]), neurodevelopmental impairment (RR: 0.91 [95% CI: 0.77-1.12]), or cognitive impairment (RR: 0.72 [95% CI: 0.35-1.45]). CONCLUSIONS: There was a 7% reduction in the risk of the composite outcome of death or BPD at 36 weeks for infants treated with iNO compared with controls but no reduction in death alone or BPD. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.

Inhaled nitric oxide in preterm infants.

OBJECTIVES: To systematically review the evidence on the use of inhaled nitric oxide (iNO) in preterm infants born at or before 34 weeks gestation age who receive respiratory support. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Studies (CENTRAL) and PsycInfo in June 2010. We also searched the proceedings of the 2009 and 2010 Pediatric Academic Societies Meeting and ClinicalTrials.gov. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts. REVIEW METHODS: Questions were developed in collaboration with technical experts, including the chair of the upcoming National Institutes of Health Office of Medical Applications of Research Consensus Development Conference. We limited our review to randomized controlled trials (RCTs) for the question of survival or occurrence of bronchopulmonary dysplasia (BPD) and for the question on short-term risks. All study designs were considered for long-term pulmonary or neurodevelopmental outcomes, and for questions about whether outcomes varied by subpopulation or by intervention characteristics. Two investigators independently screened search results, and abstracted data from eligible articles. RESULTS: We identified a total of 14 RCTs, reported in 23 articles, and eight observational studies. Mortality rates in the NICU did not differ for infants treated with iNO versus those not treated with iNO (RR 0.97 (95% CI 0.82, 1.15)). BPD at 36 weeks for iNO and control groups also did not differ (RR 0.93 (0.86, 1.003) for survivors). A small difference was found between iNO and control infants in the composite outcome of death or BPD (RR 0.93 (0.87, 0.99)). There was inconsistent evidence about the risk of brain injury from individual RCTs, but meta-analyses showed no difference between iNO and control groups. We found no evidence of differences in other short term risks. There was no evidence to suggest a difference in the incidence of cerebral palsy (RR 1.36 (0.88, 2.10)), neurodevelopmental impairment (RR 0.91 (0.77, 1.12)), or cognitive impairment (RR 0.72 (0.35, 1.45)). Evidence was limited on whether the effect of iNO varies by subpopulation or by characteristics of the therapy (timing, dose and duration, mode of delivery, or concurrent therapies). CONCLUSIONS: There was a seven percent reduction in the risk of the composite outcome of death or BPD at 36 weeks PMA for infants treated with iNO compared to controls, but no reduction in death or BPD alone. Further studies are needed to explore particular subgroups of infants and to assess long term outcomes including function in childhood. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.