Implementing an exclusive human milk diet for preterm infants: real-world experience in diverse NICUs.

BACKGROUND: Human milk-based human milk fortifier (HMB-HMF) makes it possible to provide an exclusive human milk diet (EHMD) to very low birth weight (VLBW) infants in neonatal intensive care units (NICUs). Before the introduction of HMB-HMF in 2006, NICUs relied on bovine milk-based human milk fortifiers (BMB-HMFs) when mother's own milk (MOM) or pasteurized donor human milk (PDHM) could not provide adequate nutrition. Despite evidence supporting the clinical benefits of an EHMD (such as reducing the frequency of morbidities), barriers prevent its widespread adoption, including limited health economics and outcomes data, cost concerns, and lack of standardized feeding guidelines. METHODS: Nine experts from seven institutions gathered for a virtual roundtable discussion in October 2020 to discuss the benefits and challenges to implementing an EHMD program in the NICU environment. Each center provided a review of the process of starting their program and also presented data on various neonatal and financial metrics associated with the program. Data gathered were either from their own Vermont Oxford Network outcomes or an institutional clinical database. As each center utilizes their EHMD program in slightly different populations and over different time periods, data presented was center-specific. After all presentations, the experts discussed issues within the field of neonatology that need to be addressed with regards to the utilization of an EHMD in the NICU population. RESULTS: Implementation of an EHMD program faces many barriers, no matter the NICU size, patient population or geographic location. Successful implementation requires a team approach (including finance and IT support) with a NICU champion. Having pre-specified target populations as well as data tracking is also helpful. Real-world experiences of NICUs with established EHMD programs show reductions in comorbidities, regardless of the institution's size or level of care. EHMD programs also proved to be cost effective. For the NICUs that had necrotizing enterocolitis (NEC) data available, EHMD programs resulted in either a decrease or change in total (medical + surgical) NEC rate and reductions in surgical NEC. Institutions that provided cost and complications data all reported a substantial cost avoidance after EHMD implementation, ranging between $515,113 and $3,369,515 annually per institution. CONCLUSIONS: The data provided support the initiation of EHMD programs in NICUs for very preterm infants, but there are still methodologic issues to be addressed so that guidelines can be created and all NICUs, regardless of size, can provide standardized care that benefits VLBW infants.

Early Troponin I Levels in Newborns Undergoing Therapeutic Hypothermia for Hypoxic Ischemic Encephalopathy and Residual Encephalopathy at Discharge.

OBJECTIVE: Elevation of serum troponin I has been reported in newborns with hypoxic ischemic encephalopathy (HIE), but it is diagnostic and prognostic utility for newborn under 6 hours is not clear. Study the predictive value of early serum troponin I levels in newborns with HIE undergoing therapeutic hypothermia (TH) for persistent residual encephalopathy (RE) at discharge. STUDY DESIGN: Retrospective chart review of newborns admitted with diagnosis of HIE to neonatal intensive care unit (NICU) for TH over a period of 3 years. Troponin levels were drawn with the initial set of admission laboratories while initiating TH. Newborns were followed up during hospital course and stratified into three groups based on predischarge examination and their electrical encephalography and cranial MRI findings: Group 1: no RE, Group 2: mild-to-moderate RE, and Group 3: severe RE or needing assisted medical technology or death. Demographic and clinical characteristics including troponin I levels were compared in each group. RESULTS: Out of 104 newborns who underwent TH, 65 infants were in Group 1, 26 infants in Group 2, and 13 newborns in Group 3. All groups were comparable in demographic characteristics. There was a significant elevation of serum troponin in group 2 (mild-to-moderate RE) and group 3 (severe RE) as compared with group 1 (no RE). Receiver operator curve analysis for any RE (groups 2 and 3) compared with group 1 (no RE as control) had 0.88 (0.81-0.95) area under curve, p < 0.001. A cut-off level of troponin I ≥0.12 µg/L had a sensitivity of 77% and specificity of 78% for diagnosis of any RE, positive predictive value of 68%, and a negative predictive value of 84%. CONCLUSION: In newborns undergoing TH for HIE, the elevation of troponin within 6 hours of age predicts high risk of having RE at discharge. KEY POINTS: · Troponin I elevation is a biomarker of myocardial ischemia in adults and children.. · Myocardial ischemia may be part of multi-organ injury in neonatal HIE.. · Early elevation of troponin I level may correlate with the severity of neonatal HIE and predict residual encephalopathy in newborn at discharge from initial hospitalization..

Statewide Initiative to Reduce Postnatal Growth Restriction among Infants <31 Weeks of Gestation.

OBJECTIVE: To decrease the incidence of postnatal growth restriction, defined as discharge weight <10th percentile for postmenstrual age, among preterm infants cared for in New York State Regional Perinatal Centers. STUDY DESIGN: The quality improvement cohort consisted of infants <31 weeks of gestation admitted to a New York State Regional Perinatal Center within 48 hours of birth who survived to hospital discharge. Using quality improvement principles from the Institute for Healthcare Improvement and experience derived from successfully reducing central line-associated blood stream infections statewide, the New York State Perinatal Quality Collaborative sought to improve neonatal growth by adopting better nutritional practices identified through literature review and collaborative learning. New York State Regional Perinatal Center neonatologists were surveyed to characterize practice changes during the project. The primary outcome-the incidence of postnatal growth restriction-was compared across the study period from baseline (2010) to the final (2013) years of the project. Secondary outcomes included differences in z-score between birth and discharge weights and head circumferences. RESULTS: We achieved a 19% reduction, from 32.6% to 26.3%, in postnatal growth restriction before hospital discharge. Reductions in the difference in z-score between birth and discharge weights were significant, and differences in z-score between birth and discharge head circumference approached significance. In survey data, regional perinatal center neonatologists targeted change in initiation of feedings, earlier breast milk fortification, and evaluation of feeding tolerance. CONCLUSIONS: Statewide collaborative quality improvement can achieve significant improvement in neonatal growth outcomes that, in other studies, have been associated with improved neurodevelopment in later infancy.

Vitamin D insufficiency in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Vitamin D has neuroprotective and immunomodulatory properties, and deficiency is associated with worse stroke outcomes. Little is known about effects of hypoxia-ischemia or hypothermia treatment on vitamin D status in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized vitamin D metabolism would be dysregulated in neonatal HIE altering specific cytokines involved in Th17 activation, which might be mitigated by hypothermia. METHODS: We analyzed short-term relationships between 25(OH) and 1,25(OH)2 vitamin D, vitamin D binding protein, and cytokines related to Th17 function in serum samples from a multicenter randomized controlled trial of hypothermia 33 °C for 48 h after HIE birth vs. normothermia in 50 infants with moderate to severe HIE. RESULTS: Insufficiency of 25(OH) vitamin D was observed after birth in 70% of infants, with further decline over the first 72 h, regardless of treatment. 25(OH) vitamin D positively correlated with anti-inflammatory cytokine IL-17E in all HIE infants. However, Th17 cytokine suppressor IL-27 was significantly increased by hypothermia, negating the IL-27 correlation with vitamin D observed in normothermic HIE infants. CONCLUSION: Serum 25(OH) vitamin D insufficiency is present in the majority of term HIE neonates and is related to lower circulating anti-inflammatory IL-17E. Hypothermia does not mitigate vitamin D deficiency in HIE.

Variation in Enteral Feeding Practices and Growth Outcomes among Very Premature Infants: A Report from the New York State Perinatal Quality Collaborative.

BACKGROUND: Extrauterine growth restriction (EUGR) is inversely related to neurodevelopmental outcome. We analyzed growth outcomes and enteral nutrition practices among preterm infants at New York State (NYS) regional perinatal centers (RPCs) to identify practices associated with risk of EUGR. METHODS: Surviving infants < 31 weeks' gestation admitted to a NYS RPC during 2010 were identified and data collected on their growth and enteral nutrition from a statewide database. Neonatologists at NYS RPCs were surveyed to identify center-specific nutritional practices. Survey responses, nutrition, and growth data were then analyzed to identify factors associated with risk of EUGR. RESULTS: Of the 1,387 infants, 32.6% were discharged with EUGR. Incidence of EUGR varied more than fivefold among RPCs. Nutritional practices directly related to EUGR included age at first enteral feeding and full enteral feedings. Among the surveyed nutrition practices, longer duration of trophic feeding before advancing was associated with an increased risk of EUGR while later discontinuation of total parenteral nutrition and larger trophic feeding volume were associated with lower risk. CONCLUSION: Our study found marked variation in nutrition practices and incidence of EUGR among preterm infants at NYS RPCs. A statewide quality improvement initiative to reduce practice variation and improve growth in preterm infants is underway.

Use of a Feeding Bundle Appears to Reduce Central Line Utilization in Neonates.

We investigated whether a standardized feeding bundle reduces central line utilization in very low birth weight neonates. A chart review of infants ≤1500 g requiring a central line was prepared for 2009 to 2012. Infants were stratified into 3 weight groups: ≤750 g, 751 to 1000 g, and 1001 to 1500 g. The number of central line-associated bloodstream infections (CLABSIs) was recorded. Central line utilization decreased in all of the groups: 0.45 to 0.28 in ≤750 g infants, 0.4 to 0.27 in 751 to 1000 g infants, and 0.39 to 0.3 in 1001 to 1500 g infants (all of the P < 0.001). The CLABSIs rate was unchanged. Implementation of a feeding bundle decreased central line utilization. A feeding bundle had no effect on the rate of CLABSIs.

A Multifunctional, Low Cost and Sustainable Neonatal Database System.

Continuous improvement in the clinical performance of neonatal intensive care units (NICU) depends on the use of locally relevant, reliable data. However, neonatal databases with these characteristics are typically unavailable in NICUs using paper-based records, while in those using electronic records, the inaccuracy of data and the inability to customize commercial data systems limit their usability for quality improvement or research purposes. We describe the characteristics and uses of a simple, neonatologist-centered data system that has been successfully maintained for 30 years, with minimal resources and serving multiple purposes, including quality improvement, administrative, research support and educational functions. Structurally, our system comprises customized paper and electronic components, while key functional aspects include the attending-based recording of diagnoses, integration into clinical workflows, multilevel data accuracy and validation checks, and periodic reporting on both data quality and NICU performance results. We provide examples of data validation methods and trends observed over three decades, and discuss essential elements for the successful implementation of this system. This database is reliable and easily maintained; it can be developed from simple paper-based forms or used to supplement the functionality and end-user customizability of existing electronic medical records. This system should be readily adaptable to NICUs in either high- or limited-resource environments.

Altered circulating leukocytes and their chemokines in a clinical trial of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy*.

OBJECTIVES: To determine systemic hypothermia's effect on circulating immune cells and their corresponding chemokines after hypoxic ischemic encephalopathy in neonates. DESIGN: In our randomized, controlled, multicenter trial of systemic hypothermia in neonatal hypoxic ischemic encephalopathy, we measured total and leukocyte subset and serum chemokine levels over time in both hypothermia and normothermia groups, as primary outcomes for safety. SETTING: Neonatal ICUs participating in a Neurological Disorders and Stroke sponsored clinical trial of therapeutic hypothermia. PATIENTS: Sixty-five neonates with moderate to severe hypoxic ischemic encephalopathy within 6 hours after birth. INTERVENTIONS: Patients were randomized to normothermia of 37°C or systemic hypothermia of 33°C for 48 hours. MEASUREMENTS AND MAIN RESULTS: Complete and differential leukocyte counts and serum chemokines were measured every 12 hours for 72 hours. The hypothermia group had significantly lower median circulating total WBC and leukocyte subclasses than the normothermia group before rewarming, with a nadir at 36 hours. Only the absolute neutrophil count rebounded after rewarming in the hypothermia group. Chemokines, monocyte chemotactic protein-1 and interleukin-8, which mediate leukocyte chemotaxis as well as bone marrow suppression, were negatively correlated with their target leukocytes in the hypothermia group, suggesting active chemokine and leukocyte modulation by hypothermia. Relative leukopenia at 60-72 hours correlated with an adverse outcome in the hypothermia group. CONCLUSIONS: Our data are consistent with chemokine-associated systemic immunosuppression with hypothermia treatment. In hypothermic neonates, persistence of lower leukocyte counts after rewarming is observed in infants with more severe CNS injury.

Co-Amoxiclav as empiric treatment of UTI in children: importance of surveillance in ensuring optimal empiric treatment choice.

Background Urinary tract infections are common and require prompt treatment. Objective To examine the resistance rates of co-amoxiclav in children with urinary tract infection and whether antimicrobial resistance is influenced by other variables. Methods The records and antibiotic susceptibility data of 209 patients admitted with symptomatic urinary tract infection between January 2018 and December 2019 were reviewed. Results We examined 209 patients [mean (SD) age 23.73 (32.86) months], of whom 176 (84.2%) had first urinary tract infection. Escherichia coli was isolated in 190 (90.1%). Uropathogens were sensitive to co-amoxiclav in 47.8% of patients and gentamicin in 95.2%. Combined co-amoxiclav with gentamicin demonstrated antimicrobial sensitivity in 96.2%. Antimicrobial resistance was associated with longer hospital stay (p-value < 0.02). An association was identified between co-amoxiclav resistance and recurrent urinary tract infections. Uropathogens were resistant to co-amoxiclav in 80/176 (45.5%) and 29/33 (87.9%) patients with first and recurrent urinary tract infections, respectively (p-value 0.001). No link was observed between antimicrobial resistance and atypical urinary tract infection. Conclusion Approximately half of children in this cohort had urinary tract infection due to uropathogens resistant to co-amoxiclav. Co-amoxiclav resistance is associate with recurrent infections and longer hospital stays. A combination of co-amoxiclav and gentamicin demonstrates > 96% susceptibility.

Association of Maternal Obesity and Neonatal Hypoxic-Ischemic Encephalopathy.

Objective: More women are obese at their first prenatal visit and then subsequently gain further weight throughout pregnancy than ever before. The impact on the infant's development of neonatal hypoxic ischemic encephalopathy (HIE) has not been well studied. Using defined physiologic and neurologic criteria, our primary aim was to determine if maternal obesity conferred an additional risk of HIE. Study Design: Data from the New York State Perinatal Data System of all singleton, term births in the Northeastern New York region were reviewed using the NIH obesity definition (Body Mass Index (BMI) ≥ 30 kg/m2). Neurologic and physiologic parameters were used to make the diagnosis of HIE. Physiologic criteria included the presence of an acute perinatal event, 10-min Apgar score ≤ 5, and metabolic acidosis. Neurologic factors included hypotonia, abnormal reflexes, absent or weak suck, hyperalert, or irritable state or evidence of clinical seizures. Therapeutic hypothermia was initiated if the infant met HIE criteria when assessed by the medical team. Logistic regression analysis was used to assess the effect of maternal body mass index on the diagnosis of HIE. Results: In this large retrospective cohort study we evaluated outcomes of 97,488 pregnancies. Infants born to obese mothers were more likely to require ventilatory assistance and have a lower 5-min Apgar score. After adjusting for type of delivery and maternal risk factors, infants of obese mothers were diagnosed with HIE more frequently than infants of non-obese mothers, OR 1.96 (1.33-2.89) (p = 0.001). Conclusion: Infants of obese mothers were significantly more likely to have the diagnosis of HIE.

Assessing the quantification of acetylation in konjac glucomannan via ATR-FTIR and solid-state NMR spectroscopy.

Dietary fiber like konjac glucomannan (KGM) is important in maintaining good human health. There is no established method for quantifying the average degree of acetylation DA of this polysaccharide. Polysaccharides are notoriously difficult to dissolve. In this study, KGM could not be fully dissolved in common solvents and was characterized in the solid state. ATR-FTIR spectroscopy enabled a fast qualitative assessment of acetylation, selective to the outer layer of KGM particles, and identifying excipients like magnesium stearate. Average DA was quantified for the first time with solid-state 13C NMR in KGM: semi-quantitative measurements on the same arbitrary scale by cross polarization (1 to 2 days) were calibrated with a few longer single-pulse excitation measurements (approximately 1 week). DA values ranged from 4 to 8% of the hexoses in the backbone, in agreement with previously reported values. This method could be used for quality control and standardization of KGM products.

Pneumosinus dilitans and meningioma: a case series and review of the literature.

Pneumosinus dilitans (PSD) is enlargement of the sinuses of the skull base and is frequently seen with meningiomas. Identifying PSD on imaging can assist with operative planning and preparation. Meningiomas associated with PSD are not more commonly high grade, and complete resection is frequently possible.

Surgical site infections in the NICU.

BACKGROUND: Surgical site infections (SSI) increase morbidity and mortality. In adult and pediatric populations, the incidence ranges from 1.5-12%. Studies in neonates have shown an association between preoperative stay in an intensive care unit and development of SSI. To date, there has only been a single study looking exclusively at SSI in the Neonatal Intensive Care Unit (NICU). Additionally, there has been a suggestion that prematurity may be a risk factor for SSI, but this has come from studies looking at all neonates less than 28days, rather than only neonates hospitalized in a NICU. OBJECTIVE: Primary outcome variable was to calculate the incidence of SSI in a NICU population. Secondary outcome variables were to determine if SSI is more common in premature infants and to identify additional risk factors for the development of SSI. METHODS: An IRB-approved retrospective chart review of all patients undergoing surgical procedures in a level IIIC NICU over a 2-year period was used. We utilized the CDC's definitions of surgical procedures and SSI. An epidemiologist reviewed charts if the diagnosis of SSI was questionable. Statistical analysis was done with t test and Fisher's exact test. RESULTS: We identified 165 patients who underwent 264 surgical procedures. Incidence of SSI was 11.7%. There were 31 SSI that occurred in 29 neonates over the 2-year period, with no mortality in that group. In patients who developed an SSI, 34.5% occurred after the 1st procedure, 41.4% occurred after a 2nd procedure, and 24.1% occurred after the 3rd or later procedure. There was no difference in perioperative antibiotic usage. CONCLUSIONS: This study describes SSI in a strictly neonatal population in a large academic NICU. Prematurity does not appear to be a risk factor for SSI. SSI is more common in neonates who have undergone an abdominal procedure or multiple procedures. Perioperative antibiotics are not significantly associated with prevention of SSI.

Moderate hypothermia in neonatal encephalopathy: efficacy outcomes.

Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury, but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth. This study reports a multicenter, randomized, controlled, pilot trial of moderate systemic hypothermia (33 degrees C) vs normothermia (37 degrees C) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event. The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers, and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vineland tests between normothermic and hypothermic groups. Thirty-two hypothermic and 33 normothermic neonates were enrolled. The entry criteria selected a severely affected group of neonates, with 77% Sarnat stage III. Ten hypothermia (10/32, 31%) and 14 normothermia (14/33, 42%) patients expired. Controlling for treatment group, outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers (odds ratio 10.7, 95% confidence interval 1.3-90). Severely abnormal motor scores (Psychomotor Development Index < 70) were recorded in 64% of normothermia patients and in 24% of hypothermia patients. The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group (52%) than the normothermia group (84%) (P = 0.019). Although these results need to be validated in a large clinical trial, this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury.

Moderate hypothermia in neonatal encephalopathy: safety outcomes.

Hypoxic-ischemic injury may cause multisystem organ damage with significant aberrations in clotting, renal, and cardiac functions. Systemic hypothermia may aggravate these medical conditions, such as bradycardia and increased clotting times, and very little safety data in neonatal hypoxic-ischemic injury is available. This study reports a multicenter, randomized, controlled pilot trial of moderate systemic hypothermia (33 degrees C) vs normothermia (37 degrees C) for 48 hours in infants with neonatal encephalopathy instituted within 6 hours of birth or hypoxic-ischemic event. The best outcome measures of safety were determined, comparing rates of adverse events between normothermia and hypothermia groups. A total of 32 hypothermia and 33 normothermia neonates were enrolled in seven centers. Adverse events and serious adverse effects were collected by the study team during the hospital admission, monitored by an independent study monitor, and reported to Institutional Review Boards and the Data and Safety Monitoring Committee. The following adverse events were observed significantly more commonly in the hypothermia group: more frequent bradycardia and lower heart rates during the period of hypothermia, longer dependence on pressors, higher prothrombin times, and lower platelet counts with more patients requiring plasma and platelet transfusions. Seizures as an adverse event were more common in the hypothermia group. These observed side effects of 48 hours of moderate systemic hypothermia were of mild to moderate severity and manageable with minor interventions.

Management of the late preterm infant: not quite ready for prime time.

Preterm births account for 12.5% of all births in the United States. The preterm birth rate has increased by 33% over the last 2 decades. Late and premature infants do not develop the serious and chronic conditions of the extreme premature infant. However, there is growing evidence that these infants are not as healthy as previously thought and do in fact have an increase in morbidity and mortality compared with term infants. This article summarizes the epidemiology of late preterm infants and the associated morbidities associated with their prematurity.

Working area and angle of attack in three cranial base approaches: pterional, orbitozygomatic, and maxillary extension of the orbitozygomatic approach.

OBJECTIVE: This study was designed to quantify the operative exposure obtained in the pterional, orbitozygomatic, and modified orbitozygomatic with maxillary extension surgical approaches. METHODS: The pterional and orbitozygomatic approaches and a variation of the orbitozygomatic osteotomy that included an extra centimeter of bone resection in the inferior direction ("maxillary extension") were performed on cadaveric heads. For each surgical exposure, the working area was determined by using triangles defined with anatomic points. The "angle of attack" of the approaches for the same target point was determined with the use of a robotic microscope. RESULTS: The maximum allowable angle of attack was significantly greater with the orbitozygomatic approach (37.2 +/- 4.7 degrees) than that with the pterional approach (27.1 +/- 4.3 degrees) (P < 0.001). The angle of attack with the maxillary extension (42.0 +/- 4.9 degrees) was significantly greater than that with the orbitozygomatic approach (P < 0.001). The working areas were 281, 343, and 371 mm(2) for the pterional, orbitozygomatic, and maxillary extension approaches, respectively. The orbitozygomatic approach with maxillary extension had a significantly larger working area than the pterional approach (P = 0.011). CONCLUSION: Increments in bony removal open a wider angle in which to work more than they increase the actual amount of working area. Increasing the amount of bone removed by using an orbitozygomatic approach instead of a pterional approach converts a narrow space into a wide portal, allowing surgeons to work closer to the surgical target while decreasing the need for brain retraction. Extending the orbitozygomatic approach into the maxillary region also improves the exposure area and angle, but less significantly.