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.

Resonance Raman Spectroscopy Tissue Oxygenation Measurements in Neonates.

INTRODUCTION: Current oxygen monitoring by pulse oximetry has limitations and cannot provide estimates of the oxygen content in the microvasculature, where oxygen is used. Resonance Raman spectroscopy (RRS) provides noninvasive microvascular oxygen measurement. The objectives of this study were to (i) measure the correlation between preductal RRS microvascular oxygen saturations (RRS-StO2) and central venous oxygen saturation (SCVO2), (ii) develop normative data for RRS-StO2 measurements in healthy preterm infants, and (iii) determine the effect of blood transfusion on RRS-StO2. METHODS: Thirty-three buccal and thenar RRS-StO2 measurements were performed in 26 subjects to correlate RRS-StO2 with SCVO2. Thirty-one measurements were performed in 28 subjects to develop normative RRS-StO2 values, and eight subjects were enrolled in the transfusion group to assess changes in RRS-StO2 with blood transfusion. RESULTS: There were good correlations for buccal (r = 0.692) and thenar (r = 0.768) RRS-StO2 versus SCVO2. The median RRS-StO2 in healthy subjects was 76% (IQR 68.7-80.8). There was a significant increase of 7.8 ± 4.6% in the thenar RRS-StO2 after blood transfusion. CONCLUSIONS: RRS appears to be a safe and noninvasive means of monitoring microvascular oxygenation. Thenar RRS-StO2 measurements are more feasible and practical to use than buccal. In healthy preterm infants, the median RRS-StO2 was calculated based on measurements across various gestational age and gender. More studies evaluating the effects of gestational age of RRS-StO2 in various critical clinical settings are needed to confirm the findings.

Predictors of circuit health in neonatal patients receiving extracorporeal membrane oxygenation (ECMO).

To identify predictors of neonatal ECMO circuit health, a retrospective analysis of circuit functional pressure and flow parameters as well as infant clotting values were collected 48 h prior to and 24 h post circuit change. Circuit impairment was defined as need for partial or total circuit change. Statistical analysis used multivariate statistics and non-parametric Mann-Whitney U-test with possible non-normality of measurements. A total of 9764 ECMO circuit and clotting values in 21 circuits were analyzed. Circuit delta-P mean, and maximum values increased from 8.62 to 48.59 mmHg (p < 0.011) and 16.00 to 53.00 mmHg (p < 0.0128) respectively prior to need for circuit change. Maximum and mean Pump Flow Revolutions per minute (RPM) increased by 75% (p < 0.0043) and 81% (p < 0.0057), respectively. Mean plasma free hemoglobin (pfHb) increased from 26.45 to 76.00 mg/dl, (p < 0.0209). Sweep, venous pressure, and clotting parameters were unaffected. ECMO circuit delta-P, RPM, and pfHb were early predictors of circuit impairment.

NAVA-synchronized compared to nonsynchronized noninvasive ventilation for apnea, bradycardia, and desaturation events in VLBW infants.

Neurally adjusted ventilatory assistance (NAVA) can overcome technical difficulties with synchronizing noninvasive ventilation breaths with the patient, a modality often used in very low birthweight infants (VLBW) with apnea of prematurity (AOP). This study is a retrospective single-center investigation into whether NAVA-synchronized noninvasive (niNAVA) ventilation is better than nonsynchronized (nasal intermittent positive pressure ventilation [nIPPV]) for symptomatic apnea in VLBW infants. Nursing records of apnea, bradycardia, and/or desaturations were abstracted from the electronic medical records of 108 VLBW infants admitted to the neonatal intensive care unit (NICU) from 2015 to 2017 who received either of the two modalities, 61 epochs of niNAVA totaling 488 days and 103 epochs of nIPPV totaling 886.5 days. niNAVA was associated with a significant reduction in the number of isolated bradycardic events/day (0.48 ± 0.14 vs 1.35 ± 0.27; P = .019) and overall bradycardias/day (2.42 ± 0.47 vs 4.02 ± 0.53; P = .042) and there were more epochs with no events with niNAVA compared with nIPPV (23.0% vs 6.8%; P = .004). These results justify a prospective trial of NAVA-synchronized noninvasive ventilation for VLBW infants with caffeine-resistant AOP.

Correction: Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability.

Since the publication of the above article, the authors have noted that the name of the first Item in the NRAS scoring system in Figure 1 was omitted. It is Heart Rate (C1). The authors apologise for any inconvenience caused by this error. The html and online pdf versions have now been rectified and carry the corrected Figure.

Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability.

OBJECTIVE: To test the non-inferiority of an alternative to the Apgar score. STUDY DESIGN: The Neonatal Resuscitation and Adaptation Score (NRAS) was recorded in parallel to the Apgar score by a resuscitation team at deliveries. Correlation between the systems was assessed, as well as the predictive ability of NRAS and Apgar scores for mortality or short-term morbidities. RESULTS: A total of 340 infants were in the study group. The two scores correlated strongly (r = 0.87 and 0.83 at 1 and 5 min, respectively). Those needing ventilation at 48 h of life had a 5-min NRAS < 7 in 23/26 vs Apgar < 7 (23/36, p = 0.001). A low (0-3) 1-min NRAS score was more predictive of death, 53% vs 17%, p = 0.0065. CONCLUSIONS: NRAS correlates with Apgar status assessment, and identifies newborns who die or may require further care better than the Apgar score.

Theoretical open-loop model of respiratory mechanics in the extremely preterm infant.

Non-invasive ventilation is increasingly used for respiratory support in preterm infants, and is associated with a lower risk of chronic lung disease. However, this mode is often not successful in the extremely preterm infant in part due to their markedly increased chest wall compliance that does not provide enough structure against which the forces of inhalation can generate sufficient pressure. To address the continued challenge of studying treatments in this fragile population, we developed a nonlinear lumped-parameter respiratory system mechanics model of the extremely preterm infant that incorporates nonlinear lung and chest wall compliances and lung volume parameters tuned to this population. In particular we developed a novel empirical representation of progressive volume loss based on compensatory alveolar pressure increase resulting from collapsed alveoli. The model demonstrates increased rate of volume loss related to high chest wall compliance, and simulates laryngeal braking for elevation of end-expiratory lung volume and constant positive airway pressure (CPAP). The model predicts that low chest wall compliance (chest stiffening) in addition to laryngeal braking and CPAP enhance breathing and delay lung volume loss. These results motivate future data collection strategies and investigation into treatments for chest wall stiffening.

Cardiac Troponin Levels in Neonates Who Require ECMO for Noncardiac Indications Are Elevated in Nonsurvivors.

OBJECTIVE: The aim of the study is to determine the utility of cardiac troponin (cTnI) as a marker of mortality and morbidity in newborn infants who require extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Retrospective medical chart analysis of term or near-term newborn infants treated with ECMO from 2002 to 2012 at a single Level III neonatal intensive care unit. Data analyzed included serial serum cTnI measurements, clinical and demographic characteristics, pre-ECMO laboratory values, and ECMO laboratory values and outcomes. RESULTS: Survival (27/46) was significantly related to birth weight (3,413.9 ± 662.3 vs. 2,667.7 ± 478.3 g, p < 0.001), outborn status (22/30 vs. 5/13, p = 0.0021), and the absence of a congenital diaphragmatic hernia (22/30 vs. 5/18, p = 0.0021). Mean peak cTnI did not differ between survivors and nonsurvivors but when peak cTnI was < 2.8 ng/mL, survival was 64% compared with 22% when it was > 2.8 ng/mL (p = 0.0224; odds ratio = 0.160, 95% confidence interval = 0.0292-0.8778). By multivariate analysis, peak cTnI > 2.1 was a significant risk factor for nonsurvival, p = 0.0497. The area under the curve of a receiver-operator analysis using peak cTnI > 2.1, birth weight, and birthplace was 0.89, p < 0.001. CONCLUSION: cTnI is an independent biomarker for poor outcome in neonates who receive ECMO therapy for noncardiac generations.

Aplidin reduces growth of anaplastic thyroid cancer xenografts and the expression of several angiogenic genes.

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive and highly lethal human cancers. Median survival after diagnosis is 4-6 months despite available radiotherapy and chemotherapy. Additional treatments are needed for ATC. Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulus, which is expressed by ATC. Previously, anti-VEGF antibody was used to block VEGF-dependent angiogenesis in ATC xenografts. This treatment induced partial (56%) but not complete tumor regression. Aplidin (APLD) is a marine derived antitumor agent currently in phase II clinical studies. Multiple activities of this compound have been described which likely contribute to its antiproliferative effect. Notably, APLD has been shown to have antiangiogenic properties which include: inhibition of VEGF secretion, reduction in the synthesis of the VEGF receptor (FLT-1), and blockade of matrix metalloproteinase production by endothelial cells. We hypothesized that Aplidin, with its broad spectrum of action and antiangiogenic properties, would be a potentially effective drug against ATC. METHODS: Thirty BALB/c nu/nu mice were injected with ATC cells (ARO-81, 1 x 10(6)) and allowed to implant for 3 weeks. Animals were randomized to receive daily intraperitoneal injections of vehicle, low dose (0.5 mg/kg/day), or high dose (1.0 mg/kg/day) APLD. After 3 days, the animals were killed and the tumors were removed, weighed, and divided for RNA and protein analyses. RESULTS: APLD significantly reduced ATC xenograft growth (low dose, 20% reduction, P = 0.01; high dose, 40% reduction, P < 0.001). This was associated with increased levels of apoptosis related proteins polyadenosylribose polymerase 85 (PARP-85, 75% increase, P = 0.024) and caspase 8 (greater than fivefold increase, P = 0.03). APLD treatment was further associated with lost or reduced expression of several genes that support angiogenesis to include: VEGF, hypoxia inducible factor 1(HIF-1), transforming growth factor-beta (TGFbeta), TGFbeta receptor 2 (TGFbetaR2), melanoma growth stimulating factor 1 (GRO1), cadherin, and vasostatin. CONCLUSIONS: This data supports the hypothesis that APLD may be an effective adjunctive therapy against ATC. The demonstrated molecular impact against angiogenic related genes specifically supports future strategies combining APLD with VEGF interacting agents.