Endotoxin content in neonatal formulas, fortification, and lactoferrin products: association with outcomes and guidance on acceptable limits.

While endotoxin (lipopolysaccharide) can be harmful and contribute to morbidity and mortality with Gram-negative sepsis or necrotizing enterocolitis in preterm infants, non-toxic amounts are produced as part of the neonatal microbiome and may be present in enteral nutrition and medications administered. The United States Food and Drug Administration has given guidance for endotoxin concentration limits for intravenous medications and fluids of 5 endotoxin units/kg/hour (120 endotoxin units/kg/day), but no guidance for amounts of endotoxin in enteral products. To determine baseline exposure to infants in the neonatal intensive care unit, we examined endotoxin content of enteral formulas and fortification used for preterm infants, as well as bovine lactoferrin products. We also examined endotoxin exposure and outcomes in very low birth weight infants. Endotoxin content was measured using kinetic chromogenic limulus amebocyte lysate analysis. Daily endotoxin exposure from enteral formulas ranged between < 75 to 7110 endotoxin units/kg and from lactoferrin products from 7 to 3720 endotoxin units/kg. In examining neonatal outcomes from a bovine lactoferrin product studied at three different escalating doses (100, 200, and 300 mg/kg/day), we measured endotoxin in the lactoferrin product and daily exposure was 1089 (N = 10), 2178 (N = 10) and 3287 (N = 11) endotoxin units/kg, respectively. There were no cases of necrotizing enterocolitis or mortality and no lactoferrin-related adverse effects in these patients. Enteral endotoxin daily exposures from lactoferrin products are similar to amounts in preterm enteral nutrition and appear safe and not associated with patient harm. Testing enteral products and establishing safety limits may improve care of high risk patients.

Team-Based Implementation of an Exclusive Human Milk Diet.

BACKGROUND: The University of Virginia neonatal intensive care unit is a 51-bed unit with approximately 600 to 700 admissions per year. Despite evidenced-based clinical care, necrotizing enterocolitis (NEC) and feeding intolerance remained problematic. PURPOSE: In September 2016, the neonatal intensive care unit implemented an exclusive human milk diet (EHMD) for infants born 1250 g or less with the goal of reducing NEC, feeding intolerance, parenteral nutrition use, and late-onset sepsis. Length of stay, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity were also evaluated. METHODS: A work group developed systems for charging and documenting products used in an EHMD. Outcomes were compared with a control group of similar infants born prior to the availability of the EHMD. RESULTS: Infants who received an EHMD had significantly fewer late-onset sepsis evaluations (P = .0027) and less BPD (P = .018). While not statistically significant, less surgical NEC was also demonstrated (4 cases vs 1 case, which was 57% of total NEC cases vs 14.3%) while maintaining desirable weight gain and meeting financial goals. IMPLICATIONS FOR PRACTICE: A multidisciplinary team that implements financial and documentation systems can provide a sustainable clinical practice that improves patient outcomes. Ongoing evaluations of clinical and financial data provide valuable information to guide future clinical practices related to the EHMD. IMPLICATIONS FOR RESEARCH: Future research on the anti-inflammatory effect of an EHMD is needed to provide direction regarding a potential dose-dependent response for reduced BPD rates and severity. The role of human milk and prevention or mitigation of sepsis is not fully understood, but the reduction of the number of late-onset sepsis evaluations may support the relationship between an EHMD and infection protection. Exploring clinical and financial outcomes for implementing the EHMD in infants born more than 1250 g remains a key area for research.

Advances in Trace Element Supplementation for Parenteral Nutrition.

Parenteral nutrition (PN) provides support for patients lacking sufficient intestinal absorption of nutrients. Historically, the need for trace element (TE) supplementation was poorly appreciated, and multi-TE products were not initially subjected to rigorous oversight by the United States Food and Drug Administration (FDA). Subsequently, the American Society for Parenteral and Enteral Nutrition (ASPEN) issued dosage recommendations for PN, which are updated periodically. The FDA has implemented review and approval processes to ensure access to safer and more effective TE products. The development of a multi-TE product meeting ASPEN recommendations and FDA requirements is the result of a partnership between the FDA, industry, and clinicians with expertise in PN. This article examines the rationale for the development of TRALEMENT® (Trace Elements Injection 4*) and the FDA's rigorous requirements leading to its review and approval. This combination product contains copper, manganese, selenium, and zinc and is indicated for use in adults and pediatric patients weighing ≥10 kg. Comprehensive management of PN therapy requires consideration of many factors when prescribing, reviewing, preparing, and administering PN, as well as monitoring the nutritional status of patients receiving PN. Understanding patients' TE requirements and incorporating them into PN is an important part of contemporary PN therapy.

Enteral Nutrition: The Intricacies of Human Milk from the Immune System to the Microbiome.

In 2012, the American Academy of Pediatrics stated that all preterm infant diets should consist of human milk (mother's own milk or pasteurized donor human milk). The clinical reasons supporting this policy are many, including reducing infections and retinopathy of prematurity, decreased neonatal intensive care unit length of stay, subsequent readmissions, a decrease in mortality, and improved neurodevelopmental outcomes. This article focuses on human milk, its composition and bioactive factors, and how it affects the gut-brain axis through the microbiome. We examine how differences between mother's own milk and pasteurized donor human milk affect the premature infant.

Time to regain birth weight predicts neonatal growth velocity: A single-center experience.

BACKGROUND: Failure to Thrive (FTT) describes the development of an inappropriate pattern of growth, generally secondary to inadequate nutritional intake, and is associated with several negative outcomes. We describe key features among neonates with FTT as well as the variables that predicted their growth after birth at a Neonatal Intensive Care Unit. METHODS: A retrospective single center study of 340 patients grouped into FTT (n = 100) and non-FTT (n = 240) was conducted. FTT was defined as having a weight <10th percentile on the Fenton 2013 curve at the time of discharge. For analyzing growth velocity, 204 patients were grouped into 4 quartiles based on their calculated growth velocity (grams/kilograms/day [g/kg/day]; 4th quartile had the highest velocity). Multivariate regression models were used to identify predictors of growth velocity. RESULTS: When comparing FTT vs. non-FTT patients, lower birth weights (1897.9 ± 561.4 vs. 2445.9 ± 783.0 g, t(255.1) = -7.2, p < 0.001) and higher growth velocities (9.2 ± 3.9 vs. 8.0 ± 4.1 g/kg/day, t(153.6) = 2.2, p = 0.03) were noted. Among patients with higher growth velocities, birth weights were lower (1st to 4th quartiles: 2474.0 ± 677.0, 2000.0 ± 297.0, 1715.0 ± 285.0, 1533.0 ± 332.0 g, F(3, 200) = 46.5, p < 0.001, adjusted R2 = 0.4). Days to regain birth weight was the most consistent predictor of growth velocity in our overall patient sample (ß [SE] = -0.3 [0.03], p < 0.001) and in the lowest growth velocity quartile subgroup (ß [SE] = -0.3 [0.04], p < 0.001). CONCLUSIONS: Days to regain birth weight was consistently the strongest predictor of neonatal growth velocity along with difference in gender positive predicting growth velocity in the total sample. This highlights the importance of the first week of life in growth pattern establishment.