Is Extracorporeal Membrane Oxygenation for a Neonate Ever Ethically Obligatory?

Certain interventions in the neonatal intensive care unit are considered ethically obligatory, and should be provided over parental objections. After reviewing a case, comparative outcome data, and relevant ethical principles, we propose that extracorporeal membrane oxygenation for meconium aspiration syndrome may, in some cases, be an ethically obligatory treatment.

Oral Alimentation in Neonatal and Adult Populations Requiring High-Flow Oxygen via Nasal Cannula.

Use of high-flow oxygen via nasal cannula (HFO2-NC) is increasingly common in intensive care unit (ICU) settings. Despite the critical interface between respiration and swallowing, and the high acuity of patients in ICUs, the impact of HFO2-NC on feeding and swallowing is unknown. The present prospective, single-center, cohort study investigated the impact of HFO2-NC use on oral alimentation in neonatal and adult ICU patients. Oral alimentation status was evaluated in 100 consecutive ICU inpatients (50 neonatal and 50 adult) requiring HFO2-NC. Participant characteristics, respiratory support, successful initiation of oral feeding in neonates, and successful resumption of oral feeding in adults were recorded. Seventeen of 50 (34 %) neonates requiring HFO2-NC were deemed developmentally and medically appropriate by the neonatologist and nursing to begin oral alimentation. All 17 (100 %) were successful with initiation of oral feedings. Thirty-three of 50 (66 %) continued nil per os due to prematurity or medical conditions precluding oral alimentation at time of data collection. Thirty-nine of 50 (78 %) adults requiring HFO2-NC were deemed medically appropriate by the intensivist and nursing to resume oral alimentation (n = 34) or with a functional swallow without aspiration on FEES (n = 5). All 39 (100 %) resumed oral alimentation successfully. Eleven of 50 (22 %) continued nil per os due to severe respiratory issues precluding both swallow testing and oral alimentation at time of data collection. All developmentally and medically appropriate neonatal and adult patients requiring HFO2-NC were successful with either the introduction or resumption of oral alimentation. Patients requiring HFO2-NC who are identified as having feeding or swallowing issues should be referred for swallowing evaluations using the same criteria as patients who do not require HFO2-NC, as it is not the use of HFO2-NC but rather patient-specific determinants of feeding and swallowing readiness and their underlying medical conditions that impact readiness for oral alimentation status.

Clinical and Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit in the Decade following Implementation of an Active Detection and Isolation Program.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent source of infection in the neonatal intensive care unit (NICU), often associated with significant morbidity. Active detection and isolation (ADI) programs aim to reduce transmission. We describe a comprehensive analysis of the clinical and molecular epidemiology of MRSA in an NICU between 2003 and 2013, in the decade following the implementation of an MRSA ADI program. Molecular analyses included strain typing by pulsed-field gel electrophoresis, mec and accessory gene regulator group genotyping by multiplex PCR, and identification of toxin and potential virulence factor genes via PCR-based assays. Of 8,387 neonates, 115 (1.4%) had MRSA colonization and/or infection. The MRSA colonization rate declined significantly during the study period from 2.2 to 0.5/1,000 patient days (linear time, P = 0.0003; quadratic time, P = 0.006). There were 19 cases of MRSA infection (16.5%). Few epidemiologic or clinical differences were identified between MRSA-colonized and MRSA-infected infants. Thirty-one different strains of MRSA were identified with a shift from hospital-associated to combined hospital- and community-associated strains over time. Panton-Valentine leukocidin-positive USA300 strains caused 5 of the last 11 infections. Staphylococcal cassette chromosome mec (SCCmec) types II and IVa and agr groups 1 and 2 were most predominant. One isolate possessed the gene for toxic shock syndrome toxin; none had genes for exfoliative toxin A or B. These results highlight recent trends in MRSA colonization and infection and the corresponding changes in molecular epidemiology. Continued vigilance for this invasive pathogen remains critical, and specific attention to the unique host, the neonate, and the distinct environment, the NICU, is imperative.

Neonatal sepsis 2004-2013: the rise and fall of coagulase-negative staphylococci.

OBJECTIVES: To evaluate data for the period 2004-2013 to identify changes in demographics, pathogens, and outcomes in a single, level IV neonatal intensive care unit. STUDY DESIGN: Sepsis episodes were identified prospectively and additional information obtained retrospectively from infants with sepsis while in the neonatal intensive care unit from 2004 to 2013. Demographics, hospital course, and outcome data were collected and analyzed. Sepsis was categorized as early (≤3 days of life) or late-onset (>3 days of life). RESULTS: Four hundred fifty-two organisms were identified from 410 episodes of sepsis in 340 infants. Ninety percent of cases were late-onset. Rates of early-onset sepsis remained relatively static throughout the study period (0.9 per 1000 live births). For the first time in decades, most (60%) infants with early-onset sepsis were very low birth weight and Escherichia coli (45%) replaced group B streptococcus (36%) as the most common organism associated with early-onset sepsis. Rates of late-onset sepsis, particularly due to coagulase-negative staphylococci, decreased significantly after implementation of several infection-prevention initiatives. Coagulase-negative staphylococci were responsible for 31% of all cases from 2004 to 2009 but accounted for no cases of late-onset sepsis after 2011. CONCLUSIONS: The epidemiology and microbiology of early- and late-onset sepsis continue to change, impacted by targeted infection prevention efforts. We believe the decrease in sepsis indicates that these interventions have been successful, but additional surveillance and strategies based on evolving trends are necessary.

Concurrent bloodstream infections in infants with necrotizing enterocolitis.

OBJECTIVE: To determine the incidence, microbiology, risk factors, and outcomes related to bloodstream infections (BSIs) concurrent with the onset of necrotizing enterocolitis (NEC). STUDY DESIGN: We performed a retrospective review of all cases of NEC in a single center over 20 years. BSI was categorized as "NEC-associated" if it occurred within 72 hours of the diagnosis of NEC and "post-NEC" if it occurred >72 hours afterwards. Demographics, hospital course data, microbiologic data, and outcomes were compared via univariate and multivariate analyses. RESULTS: NEC occurred in 410 infants with mean gestational age and birth weight of 29 weeks and 1290 g, respectively; 158 infants were diagnosed with at least one BSI; 69 (43.7%) with NEC-associated BSI, and 89 (56.3%) with post-NEC BSI. Two-thirds of NEC-associated BSI were due to gram-negative bacilli compared with 31.9% of post-NEC BSI (OR: 4.27; 95% CI: 2.02, 9.03) and 28.5% of all BSI in infants without NEC (OR: 5.02; 95% CI: 2.82, 8.96). Infants with NEC-associated BSI had higher odds of requiring surgical intervention (aOR: 3.51; 95% CI: 1.98, 6.24) and death (aOR: 2.88; 95% CI: 1.39, 5.97) compared with those without BSI. CONCLUSIONS: BSI is a common, underappreciated complication of NEC occurring concurrent with the onset of disease and afterwards. The microbiologic etiology of NEC-associated BSI is different from post-NEC and late-onset BSI in infants without NEC with a predominance of gram-negative bacilli. Infants with NEC-associated BSI are significantly more likely to die than those with post-NEC BSI and NEC without BSI.

Time for a neonatal-specific consensus definition for sepsis.

OBJECTIVE: To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. STUDY SELECTION: The review focused primarily on pediatric literature relevant to the topic of interest. CONCLUSIONS: Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates.

Ear drainage and the role of sepsis evaluations in the neonatal intensive care unit.

AIM: To design and implement an intervention to reduce ear drainage and subsequent sepsis evaluation and treatment in the neonatal intensive care unit. METHODS: From 2008 to 2011, we observed an increase in the rates of ear drainage warranting investigation. Data collection was performed from 1991 to 2013 on 50 cases. Preliminary analysis revealed an association between timing of endotracheal tube tape changes and onset of drainage. We speculated that pooling of anti-adhesive solution into the external auditory canal was precipitating an inflammatory process. Unit-wide education was conducted to protect the ears during tape removal. Post-initiative rates of drainage were collected and compared with pre-initiative rates. RESULTS: Median gestational age and birthweight were 26 weeks and 754 g, respectively. In 64% of cases, an anti-adhesive solution was used on the face within 48 h of the onset of drainage. Sepsis evaluation was performed in 68% of cases. Rates of ear drainage peaked from 2008 to 2011 at 9.18 per 1000 admissions when a new anti-adhesive product was used, declining to 0.66 post-initiative (rate difference: -8.52; 95% CI: -12.00, -5.03). CONCLUSION: Protecting the ear from anti-adhesive solutions during tape removal may reduce rates of noninfectious ear drainage and limit unnecessary interventions.

Novel FOXF1 deep intronic deletion causes lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins.

Haploinsufficiency of FOXF1 causes an autosomal dominant neonatally lethal lung disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). We identified novel 0.8-kb deletion within the 1.4-kb intron of FOXF1 in a deceased newborn diagnosed with ACDMPV. The deletion arose de novo on the maternal copy of the chromosome 16, and did not affect FOXF1 minigene splicing tested in lung fibroblasts. However, FOXF1 transcript level in the ACDMPV peripheral lung tissue was reduced by almost 40%. We found that, in an in vitro reporter assay, the FOXF1 intron exhibited moderate transcriptional enhancer activity, correlating with the presence of binding sites for expression regulators CTCF and CEBPB, whereas its truncated copy, which lost major CTCF and CEBPB-binding sites, inhibited the FOXF1 promoter. Our data further emphasize the importance of testing the non-protein coding regions of the genome currently not covered by diagnostic chromosomal microarray analyses or whole-exome sequencing.

Reducing MRSA Infection in a New NICU During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is prevalent in most NICUs, with a high rate of skin colonization and subsequent invasive infections among hospitalized neonates. The effectiveness of interventions designed to reduce MRSA infection in the NICU during the coronavirus disease 2019 (COVID-19) pandemic has not been characterized. METHODS: Using the Institute for Healthcare Improvement's Model for Improvement, we implemented several process-based infection prevention strategies to reduce invasive MRSA infections at our level IV NICU over 24 months. The outcome measure of invasive MRSA infections was tracked monthly utilizing control charts. Process measures focused on environmental disinfection and hospital personnel hygiene were also tracked monthly. The COVID-19 pandemic was an unexpected variable during the implementation of our project. The pandemic led to restricted visitation and heightened staff awareness of the importance of hand hygiene and proper use of personal protective equipment, as well as supply chain shortages, which may have influenced our outcome measure. RESULTS: Invasive MRSA infections were reduced from 0.131 to 0 per 1000 patient days during the initiative. This positive shift was sustained for 30 months, along with a delayed decrease in MRSA colonization rates. Several policy and practice changes regarding personnel hygiene and environmental cleaning likely contributed to this reduction. CONCLUSIONS: Implementation of a multidisciplinary quality improvement initiative aimed at infection prevention strategies led to a significant decrease in invasive MRSA infections in the setting of the COVID-19 pandemic.

Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis.

OBJECTIVE: To determine whether duration of antibiotic exposure is an independent risk factor for necrotizing enterocolitis (NEC). STUDY DESIGN: A retrospective, 2:1 control-case analysis was conducted comparing neonates with NEC to those without from 2000 through 2008. Control subjects were matched on gestational age, birth weight, and birth year. In each matched triad, demographic and risk factor data were collected from birth until the diagnosis of NEC in the case subject. Bivariate and multivariate analyses were used to assess associations between risk factors and NEC. RESULTS: One hundred twenty-four cases of NEC were matched with 248 control subjects. Cases were less likely to have respiratory distress syndrome (P = .018) and more likely to reach full enteral feeding (P = .028) than control subjects. Cases were more likely to have culture-proven sepsis (P < .0001). Given the association between sepsis and antibiotic use, we tested for and found a significant interaction between the two variables (P = .001). When neonates with sepsis were removed from the cohort, the risk of NEC increased significantly with duration of antibiotic exposure. Exposure for >10 days resulted in a nearly threefold increase in the risk of developing NEC. CONCLUSIONS: Duration of antibiotic exposure is associated with an increased risk of NEC among neonates without prior sepsis.

The impact of environmental and genetic factors on neonatal late-onset sepsis.

OBJECTIVE: To assess the genetic contribution to late-onset sepsis in twins in the newborn intensive care unit. STUDY DESIGN: A retrospective cohort analysis of twins born from 1994 to 2009 was performed on data collected from the newborn intensive care units at Yale University and the University of Connecticut. Sepsis concordance rates were compared between monozygotic and dizygotic twins. Mixed-effects logistic regression analysis was performed to determine the impact of selected nongenetic factors on late-onset sepsis. The influence of additive genetic and common and residual environmental effects were analyzed and quantified. RESULTS: One hundred seventy monozygotic and 665 dizygotic twin pairs were analyzed, and sepsis identified in 8.9%. Mean gestational age and birth weight of the cohort was 31.1 weeks and 1637 grams, respectively. Mixed-effects logistic regression determined birth weight (regression coefficient, -0.001; 95% CI, -0.003 to 0.000; P = .028), respiratory distress syndrome (regression coefficient, 1.769; 95% CI, 0.943 to 2.596; P < .001), and duration of total parenteral nutrition (regression coefficient, 0.041; 95% CI, 0.017 to 0.064; P < .001) as significant nongenetic factors. Further analysis determined 49.0% (P = .002) of the variance in liability to late-onset sepsis was due to genetic factors alone, and 51.0% (P = .001) the result of residual environmental factors. CONCLUSIONS: Our data support significant genetic susceptibility to late-onset sepsis in the newborn intensive care unit population.

Prevention of central line associated bloodstream infections in critical care units.

PURPOSE OF REVIEW: Central line associated bloodstream infections (CLABSIs) are a common source of morbidity and mortality in neonatal and pediatric intensive care units. Successful preventive strategies have recently been reported which have resulted in significant reductions in CLABSIs and their associated adverse outcomes. RECENT FINDINGS: Current surveillance data indicate a recent decline in reported CLABSI rates, likely secondary to changes in diagnostic criteria and improvements in central line care. Recent pilot randomized trials in the neonatal intensive care unit population have assessed the safety and efficacy of chlorhexidine gluconate for cutaneous antisepsis and silver alginate-impregnated dressings. No significant reductions in CLABSIs have been noted with the use of either. The greatest success has come with implementation of evidence-based catheter care bundles, which have been shown in individual units and collaborative critical care networks to significantly reduce CLABSI rates. SUMMARY: CLABSIs remain a significant problem in neonatal and pediatric critical care units, but implementation of catheter care bundles can significantly reduce rates of these infections. The safety and efficacy of chlorhexidine gluconate, silver alginate, and antibiotic-coated catheters need to be assessed via large, multicenter trials. Creation of collaborative networks may facilitate this goal.

Infections acquired during extracorporeal membrane oxygenation in neonates, children, and adults.

OBJECTIVE: To determine current rates, risk factors, and causal organisms related to infections acquired during extracorporeal membrane oxygenation (ECMO). DESIGN: A descriptive and retrospective case-control study. SETTING: ECMO centers belonging to the Extracorporeal Life Support Organization. PATIENTS: The Extracorporeal Life Support Organization Registry was queried for data related to all ECMO cases from 1998 through 2008. All culture-proven infections obtained from any site during ECMO support and not believed preexisting were included. Infection rates were analyzed by age category (i.e., neonatal, pediatric, adult), indication for ECMO (i.e., respiratory, cardiac, cardiopulmonary resuscitation), mode of ECMO (e.g., venovenous), and duration of ECMO support. Infected and noninfected ECMO patients were compared. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2,418 infections were reported during 20,741 (11.7%) ECMO cases for a rate of 15.4 per 1,000 ECMO days. Rates were highest in the adult vs. the pediatric and neonatal populations (30.6 vs. 20.8 vs. 10.1 infections per 1,000 ECMO days, respectively) and in those necessitating extracorporeal cardiopulmonary resuscitation (24.7 infections per 1,000 ECMO days). In each age category, venoarterial ECMO was the mode of support associated with the highest rate of infection. Prevalence of infection increased with duration of ECMO support from 6.1% of those requiring bypass for ≤ 7 days to 30.3% of those requiring ECMO for >14 days (p < .001). Coagulase-negative staphylococci (15.9%) were the most common organisms cultured followed by species of Candida (12.7%), and Pseudomonas (10.5%). Those with an infection acquired during ECMO support were significantly older, had a longer duration of ECMO, a longer duration of post-ECMO ventilatory support, and a higher prevalence of death than those without. CONCLUSIONS: Infections acquired during ECMO are common and can have significant associated consequences. Knowledge of high-risk patients and common causal organisms may improve strategies for treatment and prevention, but further work to develop strategies and guidelines for prevention of these infections is urgently needed.

Partial exchange transfusion for polycythemia hyperviscosity syndrome.

The objective of this study was to examine the use of partial exchange transfusion (PET) performed for polycythemia hyperviscosity syndrome (PHS) over time. A retrospective review of 141 infants who received a PET for PHS at Yale-New Haven Hospital between 1986 and 2007 was performed, querying maternal and neonatal medical records. Patient demographics, risk factors for PHS, indications for PET, and complications associated with PET and PHS were collected. Overall, there was no change in the number of PET performed over the study period ( R(2)=0.082, P=0.192). Eighty-eight percent of patients had at least one risk factor for PHS, most commonly maternal diabetes. Over time, there was a statistically significant decrease in maternal diabetes as a risk factor for PHS. Forty percent of patients had a significant complication attributed to PHS prior to PET. Eighteen percent of patients had a complication attributed to PET. Life-threatening complications of PHS or PET were rare. In conclusion, PHS continues to be a problem observed in neonatal intensive care units, particularly in at-risk populations. PHS and PET are associated with significant complications. Well-designed studies with long-term follow up are needed to assess the risks and benefits of PET for PHS.

A novel and accurate method for estimating umbilical arterial and venous catheter insertion length.

OBJECTIVE: To develop a novel, rapid, and more accurate model for estimating umbilical arterial (UAC) and venous catheter (UVC) insertion length. STUDY DESIGN: We evaluated UACs and UVCs from a retrospective cohort to determine the rate of correct initial positioning based on conventional birth weight-based equations utilized in our neonatal intensive care unit. We then derived new equations, developed the mobile application, UmbiCalc, to simplify implementation of the new equations, and validated their accuracy with prospective utilization. RESULTS: The conventional equations successfully predicted insertion length in 69% (364 of 524) of UACs and only 36% (194 of 544) of UVCs. Our new model was prospectively applied to 68 UAC and 80 UVC placements with successful initial positioning achieved in 90% [95% CI, 80.2-94.9] and 76% [95% CI, 65.9-84.2], respectively. CONCLUSIONS: Our novel approach more accurately estimates UAC and UVC insertion length.

Gastrointestinal Zygomycosis in a Preterm Neonate Associated With Contaminated Probiotics.

A neonate of 29 weeks' gestation who received probiotics developed clinical signs suggesting surgical necrotizing enterocolitis. A specimen of resected ileum revealed fungal forms within the bowel wall. Rhizopus oryzae was detected via DNA sequencing from probiotic powder and tissue specimens from the infant. To our knowledge, this is the first report linking gastrointestinal zygomycosis to the administration of contaminated probiotics.

An Initiative to Decrease Laboratory Testing in a NICU.

BACKGROUND AND OBJECTIVES: Laboratory testing is performed frequently in the NICU. Unnecessary tests can result in increased costs, blood loss, and pain, which can increase the risk of long-term growth and neurodevelopmental impairment. Our aim was to decrease routine screening laboratory testing in all infants admitted to our NICU by 20% over a 24-month period. METHODS: We designed and implemented a multifaceted quality improvement project using the Institute for Healthcare Improvement's Model for Improvement. Baseline data were reviewed and analyzed to prioritize order of interventions. The primary outcome measure was number of laboratory tests performed per 1000 patient days. Secondary outcome measures included number of blood glucose and serum bilirubin tests per 1000 patient days, blood volume removed per 1000 patient days, and cost. Extreme laboratory values were tracked and reviewed as balancing measures. Statistical process control charts were used to track measures over time. RESULTS: Over a 24-month period, we achieved a 26.8% decrease in laboratory tests performed per 1000 patient days (∽51 000 fewer tests). We observed significant decreases in all secondary measures, including a decrease of almost 8 L of blood drawn and a savings of $258 000. No extreme laboratory values were deemed attributable to the interventions. Improvement was sustained for an additional 7 months. CONCLUSIONS: Targeted interventions, including guideline development, dashboard creation and distribution, electronic medical record optimization, and expansion of noninvasive and point-of-care testing resulted in a significant and sustained reduction in laboratory testing without notable adverse effects.

Umbilical catheter-associated complications in a level IV neonatal intensive care unit.

OBJECTIVE: To assess complication rates and risks associated with the use of umbilical catheters. STUDY DESIGN: An observational cohort study was conducted in a level IV neonatal intensive care unit over 11 years. Any neonate with an umbilical catheter placed during this period was included. Complication event rates over time were assessed via Poisson and Cox regressions. RESULTS: Fifty one of 2035 umbilical arterial catheters (2.5%) and 269 of 2017 umbilical venous catheters placed (13.3%) developed a complication. Positional issues comprised most umbilical venous catheter-associated complications (86.2%) and breaks/ruptures the majority in umbilical arterial catheters (41.2%). The cumulative incidence of a complication increased most notably after 10 days of umbilical arterial catheter use and 16 days of umbilical venous catheter use. CONCLUSIONS: Complications occurred in a relatively low percentage of umbilical catheters placed in our neonatal intensive care unit. Extended catheter dwell time remains a significant risk of developing a complication.