Fetal inheritance of GP*Mur causing severe HDFN in an unrecognized case of maternal alloimmunization.

BACKGROUND: The clinical and laboratory features of hemolytic disease of the newborn can be challenging to diagnose during pregnancy in the apparent absence of a blood group antibody. Low-frequency antibodies go undetected due to the lack of appropriate antigen-positive reagent red blood cells (RBCs). CASE REPORT: A pregnant woman of Southeast Asian descent was referred to a maternal-fetal medicine outpatient clinic due to a complicated obstetric history and a negative antibody screen. This initial visit at 29 weeks and 0 days' gestational age (GA) was unremarkable. A hydropic infant, born at 29 weeks and 5 days' GA, succumbed on the seventh day of life. Comprehensive laboratory testing was performed after birth. The hospital blood bank performed a maternal antibody identification. Direct antiglobulin test was performed on the cord blood. A reference laboratory confirmed an anti-Mia , performed paternal Mia phenotyping, and identified a hybrid glycophorin B-A-B GP*Mur allele. DISCUSSION: Maternal alloimmunization to low-frequency antigens remains a challenge. Southeast Asians make up a significant percentage in some US locations. Worldwide reports on the frequency of maternal alloimmunization of the MNS system can be used to guide the use of specific reagent RBCs for testing. Such strategies rely on the identification of blood donor units for reagent manufacture and use in perinatal antibody screens. CONCLUSION: The incidence of Mia and related antibodies is significant among Southeast Asians. In North America, prenatal antibody screening cells are not routinely chosen to match this population. The clinical and societal implications are discussed.

The Relationship of Nosocomial Infection Reduction to Changes in Neonatal Intensive Care Unit Rates of Bronchopulmonary Dysplasia.

OBJECTIVE: To examine whether recent reductions in rates of nosocomial infection have contributed to changes in rates of bronchopulmonary dysplasia (BPD) in a population-based cohort. STUDY DESIGN: This was a retrospective, population-based cohort study that used the California Perinatal Quality Care Collaborative database from 2006 to 2013. Eligible infants included those less than 30 weeks' gestational age and less than 1500 g who survived to 3 days of life. Primary variables of interest were rates of nosocomial infections and BPD. Adjusted rates of nosocomial infections and BPD from a baseline period (2006-2010) were compared with a later period (2011-2013). The correlation of changes in rates across periods for both variables was assessed by hospital of care. RESULTS: A total of 22 967 infants from 129 hospitals were included in the study. From the first to second time period, the incidence of nosocomial infections declined from 24.7% to 15% and BPD declined from 35% to 30%. Adjusted hospital rates of BPD and nosocomial infections were correlated positively with a calculated 8% reduction of BPD rates attributable to reductions in nosocomial infections. CONCLUSIONS: Successful interventions to reduce rates of nosocomial infections may have a positive impact on other comorbidities such as BPD. The prevention of nosocomial infections should be viewed as a significant component in avoiding long-term neonatal morbidities.

Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk-Based Diet.

OBJECTIVE: The aim of this study was to compare outcomes of infants pre and post initiation of a feeding protocol providing an exclusive human milk-based diet (HUM). MATERIALS AND METHODS: In a multicenter retrospective cohort study, infants with a birth weight <1,250 g who received a bovine-based diet (BOV) of mother's own milk fortified with bovine fortifier and/or preterm formula were compared to infants who received a newly introduced HUM feeding protocol. Infants were excluded if they had major congenital anomalies or died in the first 12 hours of life. Data were collected 2-3 years prior to and after introduction of an exclusive HUM diet. Primary outcomes were necrotizing enterocolitis (NEC) and mortality. Secondary outcomes included late-onset sepsis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD). RESULTS: A total of 1,587 infants were included from four centers in Texas, Illinois, Florida, and California. There were no differences in baseline demographics or growth of infants. The HUM group had significantly lower incidence of proven NEC (16.7% versus 6.9%, p < 0.00001), mortality (17.2% versus 13.6%, p = 0.04), late-onset sepsis (30.3% versus 19.0%, p < 0.00001), ROP (9% versus 5.2%, p = 0.003), and BPD (56.3% versus 47.7%, p = 0.0015) compared with the BOV group. CONCLUSIONS: Extremely premature infants who received an exclusive HUM diet had a significantly lower incidence of NEC and mortality. The HUM group also had a reduction in late-onset sepsis, BPD, and ROP. This multicenter study further emphasizes the many benefits of an exclusive HUM diet, and demonstrates multiple improved outcomes after implementation of such a feeding protocol.

Platelet count and associated morbidities in VLBW infants with pharmacologically treated patent ductus arteriosus.

OBJECTIVE: Characterize the diagnosis of PDA and the distribution of pretreatment platelet count in pharmacologically managed PDA in infants ≤1500 g and assess the relationship of platelet count to serious morbidities. STUDY DESIGN: This is a retrospective, observational study. In 40 hospitals, data were collected on PDA, including pretreatment platelet count. Distribution of platelet count was examined. The association of platelet count and clinical outcomes of IVH, NEC and PDA closure prior to discharge were examined. Chi-square test was used to compare outcomes by platelet count groups. RESULTS: There were 311 patients treated with medically treated PDA. Pretreatment platelet counts were categorized as 0-119 K, 120-199 K, 200-299 K, >300 K. Incidence and grade of IVH were not significantly different by platelet group. Across all groups: No IVH 62-83%, Grades 1-2 IVH 13-25%, Grades 3-4 IVH 2-13%. NEC occurred in 0-11% of all patients studied. PDA closure rate was 33-45%. CONCLUSION: PDA closure was not significantly affected by platelet count. Platelet count was not a statistically significant factor for development of IVH and NEC in infants born <1500 g with pharmacologically treated PDA.

Aerosol particulate matter in the Baltimore metropolitan area: Temporal variation over a six-year period.

UNLABELLED: This study investigates the sources of fine particulate matter (aerodynamic diameter ≤2.5 µm; PM(2.5)) composition for the Baltimore, Maryland, metropolitan area, covering a 6-year period (2008-2013). Data obtained from the U.S. Environmental Protection Agency (EPA) Air Quality System (AQS) were used for the identification of eight chemical speciation clusters (factors), which, as a percentage of the average concentration, were identified as secondary sulfate (31.9%), secondary nitrate (14.3%), gasoline (17.4%), diesel (10.1%), soil (4.0%), biomass burning (11%), marine aerosol (4.1%), and industrial processing (7.2%). The results show predominant influence from vehicle emissions transiting major highways I-695 and I-95 located in the vicinity of the sampling site. Strong influence on PM2.5 mass from biomass burning was found in the first 2 years (2008-2009) due to particulate matter remnants from forest fire events in North Carolina and a strong contribution in 2013 that was due mainly to wood burning during winter. Sulfate, nitrate, soil, and marine aerosol fractions registered very low variability over the 6-year period analyzed. In addition, this study shows a significant reduction in particulate matter from industrial origins after a major industrial source in Baltimore shut down. The results obtained from Baltimore were compared with those from the Beltsville, Maryland, sampling station located 25 miles south of Baltimore for 2011 and 2012, where good agreement was found for most of the factors. IMPLICATIONS: This paper presents the first long-term aerosol speciation analysis in a Mid-Atlantic United States metropolitan area, which is essential for the air quality management agencies in order to revise regulations and reduce human exposure to adverse air quality conditions. The results suggest that although a declining trend in the overall PM2.5 was observed, no significant tendency was observed in the identified sources besides exceptional events such as the impact of wildfires on local air quality and downward contribution from industrial fraction of PM(2.5) after the Steel Mill at Sparrows Point closure in 2012.

Hospital variation in medical and surgical treatment of patent ductus arteriosus.

OBJECTIVE: This study aims to characterize population risks for diagnosis, medical treatment, and surgical ligation of patent ductus arteriosus (PDA) in very low-birth-weight infants. STUDY DESIGN: Maternal and neonatal data were collected in 40 hospitals in California during 2011 for infants with birth weight ≤ 1,500 g without any congenital malformation, with a diagnosis of PDA. Multivariable logistic regression was used to determine independent risks for PDA diagnosis and for surgical ligation. RESULTS: There were 770/1,902 (40.4%) infants diagnosed with PDA. Low birth weight, gestational age, respiratory distress syndrome, and surfactant administration were associated with PDA diagnosis. Ligation occurred in 43% of patients with birth weight ≤ 750 g, in 24% of patients weighing between 715 and 1,000 g, and in 12% of patients weighing from 1,001 to 1,500 g. Older gestational age (1 week, odds ratio 0.55, 95% confidence interval 0.48-0.63) and absence of respiratory distress syndrome (odds ratio 0.14, 95% confidence interval 0.03-0.59) were associated with lower ligation risk. The median hospital ligation rate was 14% (interquartile range 0-38%). CONCLUSION: Most patients with PDA receive treatment for closure. Practice variation may set the stage for further exploration of experimental trials.

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.

The local forces acting on the mechanotransduction channel in hair cell stereocilia.

In hair cells, mechanotransduction channels are located in the membrane of stereocilia tips, where the base of the tip link is attached. The tip-link force determines the system of other forces in the immediate channel environment, which change the channel open probability. This system of forces includes components that are out of plane and in plane relative to the membrane; the magnitude and direction of these components depend on the channel environment and arrangement. Using a computational model, we obtained the major forces involved as functions of the force applied via the tip link at the center of the membrane. We simulated factors related to channels and the membrane, including finite-sized channels located centrally or acentrally, stiffness of the hypothesized channel-cytoskeleton tether, and bending modulus of the membrane. Membrane forces are perpendicular to the directions of the principal curvatures of the deformed membrane. Our approach allows for a fine vectorial picture of the local forces gating the channel; membrane forces change with the membrane curvature and are themselves sufficient to affect the open probability of the channel.

Stereocilia membrane deformation: implications for the gating spring and mechanotransduction channel.

In hair cells, although mechanotransduction channels have been localized to tips of shorter stereocilia of the mechanically sensitive hair bundle, little is known about how force is transmitted to the channel. Here, we use a biophysical model of the membrane-channel complex to analyze the nature of the gating spring compliance and channel arrangement. We use a triangulated surface model and Monte Carlo simulation to compute the deformation of the membrane under the action of tip link force. We show that depending on the gating spring stiffness, the compliant component of the gating spring arises from either the membrane alone or a combination of the membrane and a tether that connects the channel to the actin cytoskeleton. If a bundle is characterized by relatively soft gating springs, such as those of the bullfrog sacculus, the need for membrane reinforcement by channel tethering then depends on membrane parameters. With stiffer gating springs, such as those from rat outer hair cells, the channel must be tethered for all biophysically realistic parameters of the membrane. We compute the membrane forces (resultants), which depend on membrane tension, bending modulus, and curvature, and show that they can determine the fate of the channel.

Nosocomial infection reduction in VLBW infants with a statewide quality-improvement model.

OBJECTIVE: To evaluate the effectiveness of the California Perinatal Quality Care Collaborative quality-improvement model using a toolkit supplemented by workshops and Web casts in decreasing nosocomial infections in very low birth weight infants. DESIGN: This was a retrospective cohort study of continuous California Perinatal Quality Care Collaborative members' data during the years 2002-2006. The primary dependent variable was nosocomial infection, defined as a late bacterial or coagulase-negative staphylococcal infection diagnosed after the age of 3 days by positive blood/cerebro-spinal fluid culture(s) and clinical criteria. The primary independent variable of interest was voluntary attendance at the toolkit's introductory event, a direct indicator that at least 1 member of an NICU team had been personally exposed to the toolkit's features rather than being only notified of its availability. The intervention's effects were assessed using a multivariable logistic regression model that risk adjusted for selected demographic and clinical factors. RESULTS: During the study period, 7733 eligible very low birth weight infants were born in 27 quality-improvement participant hospitals and 4512 very low birth weight infants were born in 27 non-quality-improvement participant hospitals. For the entire cohort, the rate of nosocomial infection decreased from 16.9% in 2002 to 14.5% in 2006. For infants admitted to NICUs participating in at least 1 quality-improvement event, there was an associated decreased risk of nosocomial infection (odds ratio: 0.81 [95% confidence interval: 0.68-0.96]) compared with those admitted to nonparticipating hospitals. CONCLUSIONS: The structured intervention approach to quality improvement in the NICU setting, using a toolkit along with attendance at a workshop and/or Web cast, is an effective means by which to improve care outcomes.

Decreasing central line associated bloodstream infection in neonatal intensive care.

Central Line Associated Bloodstream Infections (CLABSIs) have come to be recognized as preventable adverse events that result from lapses in technique at multiple levels of care. CLABSIs are associated with increased mortality and adverse outcomes that may have lifelong consequences. This review provides a summary of evidence-based strategies to reduce CLABSI in the newborn intensive care unit that have been described in the literature over the past decades. Implementation of these strategies in "bundles" is also discussed, citing examples of successful quality improvement collaboratives. The methods of implementation require an understanding of the scientific data and technical developments, as well as knowledge of how to influence change within the unique and complicated milieu of the newborn intensive care unit.

Implementation and case-study results of potentially better practices to improve pain management of neonates.

OBJECTIVE: Collaborative quality improvement techniques were used to facilitate local quality improvement in the management of pain in infants. Several case studies are presented to highlight this process. METHODS: Twelve NICUs in the Neonatal Intensive Care Quality Improvement Collaborative 2002 focused on improving neonatal pain management and sedation practices. These centers developed and implemented evidence-based potentially better practices for pain management and sedation in neonates. The group introduced changes through plan-do-study-act cycles and tracked performance measures throughout the process. RESULTS: Strategies for implementing potentially better practices varied between centers on the basis of local characteristics. Individual centers identified barriers to implementation, developed tools for improvement, and shared their experience with the collaborative. Baseline data from the 12 sites revealed substantial opportunities for improved pain management, and local potentially better practice implementation resulted in measurable improvements in pain management at participating centers. CONCLUSIONS: The use of collaborative quality improvement techniques enhanced local quality improvement efforts and resulted in effective implementation of potentially better practices at participating centers.

Prospective evaluation of postnatal steroid administration: a 1-year experience from the California Perinatal Quality Care Collaborative.

OBJECTIVE: Postnatal steroids (PNSs) are used frequently to prevent or treat chronic lung disease (CLD) in the very low birth weight (VLBW) infant, and their use continues despite concerns regarding an increased incidence of longer-term neurodevelopmental abnormalities in such infants. More recently, there has been a suggestion that corticosteroids may be a useful alternative therapy for hypotension in VLBW infants, but there have been no prospective reports of such use for a current cohort of VLBW infants. METHODS: The California Perinatal Quality Care Collaborative (CPQCC) requested members to supplement their routine Vermont Oxford Network data collection with additional information on any VLBW infant treated during their hospital course with PNS, for any indication. The indication, actual agent used, total initial daily dose, age at treatment, type of respiratory support, mean airway pressure, fraction of inspired oxygen, and duration of first dosing were recorded. RESULTS: From April 2002 to March 2003 in California, 22 of the 62 CPQCC hospitals reported supplemental data, if applicable, from a cohort of 1401 VLBW infants (expanded data group [EDG]), representing 33.2% of the VLBW infants registered with the CPQCC during the 12-month period. PNSs for CLD were administered to 8.2% of all VLBW infants in 2003, 8.6% of infants in the 42 hospitals that did not submit supplemental data (routine data-set group, compared with 7.6% in EDG hospitals). Of the 1401 VLBW infants in the EDG, 19.3% received PNSs; 3.6% received PNSs for only CLD, 11.8% for only non-CLD indications, and 4.0% for both indications. At all birth weight categories, non-CLD use was significantly greater than CLD use. The most common non-CLD indication was hypotension, followed by extubation stridor, for which 36 (16.3%) infants were treated. For hypotension, medications used were hydrocortisone followed by dexamethasone. Infants treated with PNSs exclusively for hypotension had a significantly higher incidence of intraventricular hemorrhage, periventricular leukomalacia, and death when compared with infants treated only for CLD or those who did not receive PNSs. CONCLUSIONS: The common early use of hydrocortisone for hypotension and the high morbidity and mortality in children receiving such treatment has not been recognized previously and prospective trials evaluating the short- and long-term risk/benefit of such treatment are urgently required.

Implementation of evidence-based potentially better practices to decrease nosocomial infections.

OBJECTIVE: Six neonatal intensive care units (NICUs) that are members of the Vermont Oxford National Evidence-Based Quality Improvement Collaborative for Neonatology collaborated to reduce infection rates. There were 7 centers in the original focus group, but 1 center left the collaborative after 1 year. Nosocomial infection is a significant area for improvement in most NICUs. METHODS: Six NICUs participating in the Vermont Oxford Network made clinical changes to address 3 areas of consensus: handwashing, line management, and accuracy of diagnosis. The summary statements were widely communicated. Review of the literature, internal assessments, and benchmarking visits all contributed to ideas for change. RESULTS: The principle outcome was the incidence of coagulase-negative staphylococcus bacteremia. There was an observed reduction from 24.6% in 1997 to 16.4% in 2000. CONCLUSIONS: The collaborative process for clinical quality improvement can result in effective practice changes.