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Gustave H Falciglia,1,2 Hernan Sierra-Fernandez,3 Melissa Freeman,2 Daniel Healy,2 Jennifer S Wicks,1,2 Daniel T Robinson1,2 1Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 2Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 3Department of Pediatrics, Rush University Medical Center, Chicago, IL, USACorrespondence: Gustave H Falciglia, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave, Box #45, Chicago, IL, 60611, USA, Tel +1 312 848-3142, Email gustave-falciglia@northwestern.eduPurpose: Few clinical decision support systems (CDSSs) are available to help clinicians calculate nutrition intake in infants in the neonatal intensive care unit (NICU) despite improvement in the accuracy of calculations and quality of nutrition delivered. The aim of this manuscript is to qualitatively define the barriers associated with the implementation of CDSSs to calculate fluid and nutrition intake.Methods: After defining the data necessary to calculate fluid and nutrition intake, multidisciplinary groups analyzed CDSS capabilities and barriers to implementation at two academically affiliated NICUs. They implemented CDSSs to calculate intake received in the past (retrospective) and to estimate future intake from orders (prospective). Barriers and measures to reduce them are reported.Results: Barriers to implementation include simultaneous enteral feeding orders, the use of free text in the electronic health record (EHR), and a large variety of enteral feeding types for clinical use. These barriers made implementation of prospective CDSSs more difficult. CDSSs reported values that were normalized by both the most recent measured weight (usually obtained daily) and a dosing weight, a weight updated less frequently and used by pharmacies to facilitate prescribing.Conclusion: Despite using an EHR from the same vendor, different solutions were implemented at each NICU. CDSSs improved access to individual infant data on fluid and nutrition intake; however, none of the CDSSs easily exported data to monitor the quality of intake for the entire NICU or specific populations (eg, infants with bronchopulmonary dysplasia). Comprehensive CDSSs that include prospective intake and monitor the quality of nutrition intake through standardized values will require continued investigation and resources.Keywords: clinical decision support, nutrition, infant, neonatal intensive care unit

The unprecedented use of Earth's resources by humans, in combination with increasing natural variability in natural processes over the past century, is affecting the evolution of the Earth system. To better understand natural processes and their potential future trajectories requires improved integration with and quantification of human processes. Similarly, to mitigate risk and facilitate socio-economic development requires a better understanding of how the natural system (e.g. climate variability and change, extreme weather events, and processes affecting soil fertility) affects human processes. Our understanding of these interactions and feedback between human and natural systems has been formalized through a variety of modelling approaches. However, a common conceptual framework or set of guidelines to model human-natural-system feedbacks is lacking. The presented research lays out a conceptual framework that includes representing model coupling configuration in combination with the frequency of interaction and coordination of communication between coupled models. Four different approaches used to couple representations of the human and natural system are presented in relation to this framework, which vary in the processes represented and in the scale of their application. From the development and experience associated with the four models of coupled human-natural systems, the following eight lessons were identified that if taken into account by future coupled human-natural-systems model developments may increase their success: (1) leverage the power of sensitivity analysis with models, (2) remember modelling is an iterative process, (3) create a common language, (4) make code open-access, (5) ensure consistency, (6) reconcile spatio-temporal mismatch, (7) construct homogeneous units, and (8) incorporating feedback increases non-linearity and variability. Following a discussion of feedbacks, a way forward to expedite model coupling and increase the longevity and interoperability of models is given, which suggests the use of a wrapper container software, a standardized applications programming interface (API), the incorporation of standard names, the mitigation of sunk costs by creating interfaces to multiple coupling frameworks, and the adoption of reproducible workflow environments to wire the pieces together.

Background: Bereaved mothers describe positive experiences donating breast milk and negative experiences when not informed of opportunities to donate. Predictors of whether mothers donate milk are unknown, impairing efforts to optimize support in completing donation. Objective: To define circumstances associated with completing mother's milk (MM) donation during bereavement. Methods: A retrospective cohort study included dyads of bereaved mothers and their deceased children if a child's death occurred on-site at a quaternary care children's hospital during 2016-2020, the child had documentation of MM availability, and age at death <24 months. The primary outcome was the completion of MM donation to the milk bank. Multivariate logistic regression measured associations between clinical variables and odds of completion. Results: Of 124 deceased children with documented MM exposure, 34 mothers (28%) of 35 of those children completed MM donation, donating a mean of 13.7 liters (SD 16.8). The child's race/ethnicity documented in the medical record was White for 25 (71%), Black/African American (AA) for 1 (3%), Asian for 1 (3%), and Hispanic/Latino for 8 (23%). Referenced to mothers of White children, being a mother of an AA [OR 0.05 (95% CI: 0.01-0.43)] or Asian [0.08 (0.01-0.75)] child was associated with lower odds of donation. Referenced to mothers delivering full term (≥37 weeks'), mothers delivering <34 weeks showed higher odds [5.0 (1.5-17.5)] of donation. Conclusion: Relatively few bereaved mothers of children with indicators of MM exposure completed donation. The results suggest an opportunity to ensure bereaved mothers are uniformly informed and supported in donating.

Close attention to nutritional management is essential for optimizing growth and neurodevelopment of the preterm infant. Protein intake and the protein to energy ratio are the main determinants of growth and body composition. Yet large, multi-center, randomized controlled trials are lacking to guide protein delivery for the preterm infant. Until these studies are pursued, smaller trials must be used to inform clinical practice. This review summarizes the randomized controlled trials that have been performed to test the impact of higher vs. lower protein delivery to the preterm infant. We consider the trials that varied protein delivery rates during parenteral and enteral phases of nutrition. Considerable heterogeneity exists across study designs. Still, cumulative evidence from these trials provides a framework for current recommendations for protein intake in the preterm infant., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Use of parenteral nutrition (PN) in the neonatal intensive care unit (NICU) requires evaluating the need for central venous catheters, potential drug incompatibilities, unintentional exposures, and suboptimal energy and nutrient intake during the transition to full enteral nutrition. Risks of photooxidation reactions in PN components, refeeding syndrome, and excess early amino acid intake should prompt the reevaluation of routine practices. The goal of this paper is to review the practicalities, challenges, and conundrums of administering PN in the NICU., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population., Methods: An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN-associated liver disease (PNALD) at study entry were excluded., Results: The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided., Conclusion: Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022-2023 Board of Directors., (© 2023 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

In the United States, 10% of infants are born preterm (PT; <37 weeks gestational age) each year and are at higher risk of complications compared to full term infants. The burden of PT birth is borne disproportionately by Black versus non-Black families, with Black mothers significantly more likely to give birth to a PT infant. One proven strategy to improve short- and long-term health outcomes in PT infants is to feed mother's own milk (MOM; breast milk from the mother). However, mothers must make decisions about work and MOM provision following PT birth, and more time spent in paid work may reduce time spent in unpaid activities, including MOM provision. Non-Black PT infants are substantially more likely than Black PT infants to receive MOM during the birth hospitalization, and this disparity is likely to be influenced by the complex decisions mothers of PT infants make about allocating their time between paid and unpaid work. Work is a social determinant of health that provides a source of income and health insurance coverage, and at the same time, has been shown to create disparities through poorer job quality, lower earnings, and more precarious employment in racial and ethnic minority populations. However, little is known about the relationship between work and disparities in MOM provision by mothers of PT infants. This State of the Science review synthesizes the literature on paid and unpaid work and MOM provision, including: (1) the complex decisions that mothers of PT infants make about returning to work, (2) racial and ethnic disparities in paid and unpaid workloads of mothers, and (3) the relationship between components of job quality and duration of MOM provision. Important gaps in the literature and opportunities for future research are summarized, including the generalizability of findings to other countries.

Refeeding syndrome (RS) in preterm infants is a scenario of fetal malnutrition, primarily resulting from placental insufficiency, followed by a postnatal physiologic adaptation and response to an imbalance of nutrients provided parenterally. Growth restriction and small gestational age status are common findings in infants at risk of developing RS. Adverse clinical outcomes associated with RS may be severe and life-threatening. The biochemical abnormalities that occur in RS may be mitigated through careful monitoring and adaptation of the clinical management of parenteral and enteral nutrition. This perspective reviews the physiology and metabolism in infants with RS and provides suggested approaches to their clinical monitoring and nutritional management., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Body composition analysis to distinguish between fat mass and fat-free mass is an established research approach to assess nutritional status. Within neonatal medicine, preterm infant body composition is linked with later health outcomes including neurodevelopment and cardiometabolic health. Mounting evidence establishing fat-free mass as an indicator of nutritional status, coupled with the availability of testing approaches that are feasible to use in preterm infants, have enhanced interest in measuring body composition in the neonatal intensive care unit (NICU) setting. In this paper, we use the concept of clinical utility-the added value of a new methodology over current standard care-as a framework for assessing several existing body composition methodologies with potential for clinical application to preterm neonates. We also use this framework to identify remaining knowledge gaps and prioritize efforts to advance our understanding of clinically-oriented body composition testing in the NICU., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Maternal prepregnancy body mass index (BMI) represents a surrogate marker of fetal exposures to the maternal metabolism during pregnancy. Yet, it remains poorly understood whether this marker indicates risk of altered trajectories in postnatal growth and development in children born preterm. This study aimed to determine whether maternal prepregnancy BMI is associated with altered growth and development in children born preterm., Study Design: A retrospective cohort study evaluated prepregnancy BMI as the exposure for childhood outcomes using linear regression and mixed effects models. The 38 children included in this follow-up evaluation originally participated in a prospective, observational cohort study to determine longitudinal levels of lipid species in preterm human milk expressed by women who delivered prior to 32 weeks. Childhood outcomes in this study were anthropometric measures during hospitalization ( n  = 38), after discharge through 36 months ( n  = 34) and Bayley-III developmental scores through 18 months corrected age ( n  = 26)., Results: In 38 children born prior to 32 weeks, higher maternal prepregnancy BMI was independently associated with higher preterm infant growth velocity during hospitalization, but not associated with in-hospital change in length or head circumference and/or postdischarge growth. In univariate linear regression models, higher maternal BMI was associated with lower cognitive scores at 18 months corrected age. This significant association remained in an adjusted model accounting for relevant influences on early childhood development., Conclusion: Increasing maternal prepregnancy BMI may reflect risk of altered growth and cognitive development in children born preterm., Key Points: · Maternal BMI was associated with early preterm infant weight gain.. · Maternal BMI was not associated with postdischarge growth.. · Increased maternal BMI may be associated with lower cognitive function scores in offspring.., Competing Interests: None declared., (Thieme. All rights reserved.)

Preterm and critically ill infants are at risk for hypertriglyceridemia (HTG). Common risk factors for HTG include prematurity, intravenous lipid emulsion dose and oil composition, reduced lipoprotein lipase activity, fetal growth restriction, sepsis, and renal failure. Despite these risk factors, clinicians lack a universally agreed upon definition for HTG and evidence-based approach to HTG management. This review provides a detailed overview of triglyceride and intravenous lipid emulsion metabolism and how this relates to specific HTG risk factors, along with some practical considerations for managing HTG in the neonatal population., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: The COVID-19 pandemic presents unique challenges to maternity settings. Its influence on providing in-hospital lactation support has not been well described., Research Aim: To describe the experiences of healthcare workers as they provided in-hospital lactation support during the pandemic., Methods: A prospective, cross-sectional, online survey evaluated healthcare providers working with postpartum women and newborns affected by COVID-19 at an academic center during March-June 2020. Providers were queried regarding the influence of COVID-19 and COVID-19-specific policies on providing lactation support. Questions assessed guidance received, perceived stress, difficulty providing care, and solicited qualitative responses. The constant comparative method was used to analyze qualitative data., Results: Of 108 providers, 70 (65%) completed the survey. Of 57 providing direct lactation support to women affected by COVID-19, most ( n = 39, 67%) reported increased stress. Participants reported lower stress scores when receiving guidance through shift meetings or email compared to those not receiving this guidance [stress score with shift meeting guidance ( M [ SD ]): 3.10 (0.88); score without guidance: 3.83 (0.66); n = 39, p = .009; score with email guidance: 3.79 (0.58); score without guidance: 4.50 (0.58); n = 18, p = .045). Qualitative responses ( n = 67; 96%) identified three themes: visitor restrictions allowed less distraction during lactation support; physical separation disrupted maternal/infant bonding; workflow challenges resulted from policy changes and supply access., Conclusions: Most participating staff providing lactation support to participants affected by COVID-19 reported increased stress. Ensuring written or verbal guidance may reduce staff's experiences of stress. Efforts to optimize lactation support during COVID-19 should consider reducing distractions, physical separation, and logistic challenges.

Growing evidence demonstrates human milk's protective effect against necrotizing enterocolitis (NEC). Human milk derives these properties from biologically active compounds that influence intestinal growth, barrier function, microvascular development, and immunological maturation. Among these protective compounds are growth factors that are secreted into milk with relatively high concentrations during the early postnatal period, when newborns are most susceptible to NEC. This paper reviews the current knowledge on human milk growth factors and their mechanisms of action relevant to NEC prevention. It will also discuss the stability of these growth factors with human milk pasteurization and their potential for use as supplements to infant formulas with the goal of preventing NEC.

Although crucial in improving health outcomes in the preterm infants, parenteral nutrition (PN) is not without risk, especially if handled improperly. A growing body of evidence suggests that components of PN admixtures, including lipid injectable emulsions (ILEs), are susceptible to degradation, including oxidation when exposed to light (ie, photo-oxidation), resulting in the production of reactive oxygen species. Infants, especially those born preterm, are considered more susceptible to consequences of oxidative stress than children and adults. Oxidative stress is associated with bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intestinal failure-associated liver disease. The American Society for Parenteral and Enteral Nutrition (ASPEN) assembled a working group to provide recommendations on clinical practice surrounding photoprotection of PN.This Position Paper reviews the scientific literature on the formation of quantifiable peroxides and other degradation products when PN admixtures and ILEs are exposed to light and reports adverse clinical outcomes in premature infants exposed to PN. Recommendations for photoprotection of PN admixtures and ILEs are provided, as well as the challenges in achieving complete photoprotection with the equipment, supplies, and materials currently available in the US. ASPEN and the authors understand that the full implementation of complete photoprotection may not currently be feasible given current product availability; recommendations provided in this paper serve to represent the goal to which to strive as well as to highlight the importance of product availability to achieve these practices. This paper has been approved by the ASPEN Board of Directors., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background: Evidence documenting whether diet quality, particularly dietary fatty acids, is associated with preterm birth (PTB) is limited., Objective: The aim was to measure associations between dietary fatty acid intake prior to pregnancy, specifically n-3 (ɷ-3) PUFAs and odds of PTB in US women and determine if associations differed by prepregnancy BMI., Methods: We designed a secondary analysis of dietary intake in nulliparous women enrolled in a longitudinal cohort (NCT01322529). Participants completed an FFQ, modified to assess detailed PUFA intake, during the 3 mo preceding pregnancy. Inclusion in this analytic cohort required total energy intake within 2 SDs of the group mean. Prepregnancy BMI was categorized as underweight, normal, overweight, or obese. The primary exposure was estimated intake of EPA and DHA (combined EPA+DHA), in the context of a recommended intake of 250 mg. The primary outcome was PTB (<37 wk). Adjusted regression models controlled for maternal factors relevant to PTB and evaluated associations with PUFAs. Interaction terms estimated effect modification of BMI. A false discovery rate (FDR) correction accounted for multiple comparisons., Results: Median daily intake of combined EPA+DHA in 7365 women was 70 mg (IQR: 32, 145 mg). A significant interaction term indicated the effects of EPA+DHA on odds of PTB were different for different BMI categories ( P  < 0.01). Specifically, higher intake of combined EPA+DHA was nominally associated with reduced odds of PTB in women with underweight (OR: 0.67; 95% CI: 0.46-0.98) and normal BMI (OR: 0.87; 95% CI: 0.78-0.96), yet was associated with increased odds of overweight BMI (OR: 1.21; 95% CI: 1.02-1.44). Associations remained significant after FDR correction., Conclusions: Based on a cohort of US women designed to identify predictors of adverse pregnancy outcomes, dietary intake of combined EPA+DHA was considerably lower than recommended. Associations between intake of these recommended n-3 fatty acids and risk of PTB differ by maternal BMI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation., Study Design: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks., Results: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003)., Conclusions: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life., Trial Registration: Clinicaltrials.gov: NCT03192839., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Human milk samples were prospectively obtained from women who delivered prior to the 32nd week of gestation [1]. The 36 preterm human milk samples analysed in this dataset were collected at week 1 and week 4 of lactation. Samples were categorized as being from women with normal pre-pregnancy body mass index (BMI 18-24.9 kg/m 2 ) versus overweight/obese (BMI ≥25). Whole milk samples were frozen at -80 Celsius without prior processing and shipped for analysis on dry ice. Untargeted metabolomic and lipidomic platforms using UPLC-MS/MS and infusion-MS analysis for select lipids were performed by Metabolon. Lipidomic analysis included detection of complex lipids found in the milk fat globule membrane. Data were categorized by maternal BMI, week of lactation as well as gestational age at delivery. Data sheets are separated based on whether they report metabolomics versus lipidomics, as well as whether they report output from samples collected at week 1 versus week 4 of lactation. These data allow calculating relationships between clinical variables and human milk components. As an illustrative example, correlations between pre-pregnancy BMI and total milk fatty acids were calculated for this report using the Spearman correlation. These data will inform scientists of variability in milk composition attributable to maternal pre-pregnancy BMI as well as changes in milk composition as milk matures during lactation from week 1 to week 4. These data may best be used for generating hypotheses and justification of future work investigating whether maternal pre-pregnancy body mass index impacts preterm human milk composition., Competing Interests: None., (© 2020 The Authors.)

Objective: To estimate the association of continuity of neonatologist care with caloric intake and growth velocity (GV) in very low birth weight (VLBW) infants., Study Design: We created a daily continuity index (DCI) defined as the number of days the neonatologist worked in the previous week. We estimated the independent associations between this index and infants' daily caloric intake (kcal/kg/day) and GV (g/kg/day) through the first 6 weeks of life using regression analyses., Results: Twenty-eight neonatologists cared for 115 infants over 4643 patient-days. The DCI was independently associated with increased caloric intake (β = 1.27 kcal/kg/day per each day of continuity, p < 10 -4 ); this effect was magnified (β = 3.33, p < 10 -4 ) in the first 2 weeks. No association was observed between the index and GV., Conclusions: Neonatologist continuity may contribute to caloric intake in VLBW infants. Quality metrics focused on this area of health care delivery warrant further discovery.

Distributed measurements of agricultural erosion at the farm-scale are needed to evaluate both the on and off-site impacts of sediment redistribution. While best management practices have been shown to reduce surface erosion rates and improve water quality, their farm-scale effects can be difficult to quantify. In this study we use imagery from an unmanned aerial vehicle (UAV) and structure-from-motion multi-view stereo (SfM-MVS) to quantify erosion rates and their effects on crop yield across a 15.9-ha agricultural field. Our results highlight that the installation of catch basins were able to stop 159.52 t of sediment and associated nutrients from entering the waterway adjacent to the study site over the course of one year, corresponding to an erosion rate of 18.83 t ha -1  yr -1 across six study basins. Poor soil structure resulting from downslope tillage reduced crop yields on topographic shoulders of the study site, while accelerated water erosion processes were responsible for large areas of washout that caused highly variable crop growth in footslopes. The highest crop yields were associated with backslopes and topographically flat regions of the field which experienced minimal erosion. Change-detection results showed that UAV imagery was able to reliably quantify depositional plumes and was comparable to that of a terrestrial laser scanner (TLS) using a ± 0.04 m confidence interval., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Clinical decision support (CDS) improves nutrition delivery for infants in the neonatal intensive care unit (NICU), however, the prevalence of CDS to support nutrition is unknown., Methods: Online surveys, with telephone and email validation of responses, were administered to NICU clinicians in the Children's Hospital Neonatal Consortium (CHNC). We determined and compared the availability of CDS to calculate calories and fluid received in the prior 24 h, stratified by enteral and parenteral intake, using McNemar's test., Results: Clinicians at all 34 CHNC hospitals responded with 98 of 108 (91%) surveys completed. NICUs have considerably less CDS to calculate enteral calories received than enteral fluid received (32% vs. 82%, p < 0.001) and less CDS to calculate parenteral calories received than parenteral fluid received (29% vs. 82%, p < 0.001)., Discussion: Most CHNC NICUs are unable to reliably and consistently monitor caloric intake delivered to critically ill infants at risk for growth failure.

The clinical goals of intravenous lipid emulsions (ILEs) have changed since their initial development. In the past, 100% soybean oil was used to provide energy and prevent an essential fatty acid deficiency. Now, different oil sources are used with the goal of improving nutritional status and preventing common neonatal comorbidities. We now have a better understanding of specific ILE constituents, namely, fatty acids, vitamin E, and phytosterols, and how these components contribute to complications such as intestinal failure-associated liver disease. This review addresses the development and composition of different ILEs and summarizes how individual ILE ingredients affect infant metabolism and health., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: Mother's milk is the recommended source of nutrition for all newborns. Preterm infants may be further compromised by maternal factors that impede successful lactation and alter milk composition., Purpose: To review and summarize the state of the science regarding implications of maternal overweight and obesity on successful lactation and associated alterations in preterm mother's milk composition., Methods/search Strategy: PubMed, EMBASE, and Web of Science searches were performed using relevant key words to identify references addressing maternal overweight or obesity, prematurity, human milk, and lactation., Findings/results: In the United States, more than half of women enter pregnancy with an overweight or obese body mass index. These women have increased risk of adverse pregnancy outcomes and obstetric complications that can undermine successful initiation and continuation of lactation, including preterm birth. Maternal overweight and obesity are also associated with alterations in mother's milk composition., Implications for Practice: Mother-preterm infant dyads affected by maternal overweight and obesity are at risk for barriers to initiation and continuation of lactation. Support for early initiation of milk expression is needed. Continued support, especially during the first weeks of lactation, can facilitate sustained milk production., Implications for Research: Considerable knowledge gaps remain in this area of human milk science. Future research is needed to facilitate more comprehensive understanding of differences in milk composition associated with maternal overweight and obesity and their impact on clinical outcomes in the preterm infant.

Concordance among wetland physicochemical conditions, vegetation, and surrounding land cover may result from the influence of land cover on the sources of plant propagules, on physicochemical conditions, and their subsequent determination of growing conditions. Alternatively, concordance may result if differences in climate, soils, and species pools are spatially confounded with differences in human population density and land conversion. Further, we expect that land cover within catchment boundaries will be more predictive than land cover in symmetrical buffers if runoff is a major pathway. We measured concordance between land cover, wetland vegetation and physicochemical conditions in 48 prairie pothole wetlands, controlling for inter-wetland distance. We contrasted land-cover data collected over a four-year period by multiple extraction approaches including topographically-delineated catchments and nested 30 m to 5,000 m radius buffers. After factoring out inter-wetland distance, physiochemical conditions were significantly concordant with land cover. Vegetation was not significantly concordant with land cover, though it was strongly and significantly concordant with physicochemical conditions. More, concordance was as strong when land cover was extracted from buffers <500 m in radius as from catchments, indicating the mechanism responsible is not topographically constrained. We conclude that local landscape structure does not directly influence wetland vegetation composition, but rather that vegetation depends on 1) physicochemical conditions in the wetland that are affected by surrounding land cover and on 2) regional factors such as the vegetation species pool and geographic gradients in climate, soil type, and land use., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the association between nutrition delivery practices and energy and protein intake during the transition from parenteral to enteral nutrition in infants of very low birth weight (VLBW)., Study Design: This was a retrospective analysis of 115 infants who were VLBW from a regional neonatal intensive care unit. Changes in energy and protein intake were estimated during transition phase 1 (0% enteral); phase 2 (>0, ≤33.3% enteral); phase 3 (>33.3, ≤66.7% enteral); phase 4 (>66.7, <100% enteral); and phase 5 (100% enteral). Associations between energy and protein intake were determined for each phase for parenteral nutrition, intravenous lipids, central line, feeding fortification, fluid restriction, and excess non-nutritive fluid intake., Results: In phases 2 and 3, infants receiving feeding fortification received less protein than infants who were unfortified (-1.1 and -0.3 g/kg/d, respectively; P < .001). However, this negative association was not observed after adjusting for relevant nutrition delivery practices. Despite greater enteral protein intake during phases 2 and 3 (0.3 and 0.8 g/kg/d, respectively; P < .001), infants with early fortification received less parenteral protein than infants who were unfortified (-1.4 and -1.1 g/kg/d, respectively; P < .001). Similar patterns were observed for energy intake. Protein intake declined during phases 3 and 4., Conclusions: Infants paradoxically received less protein and energy on days with early fortification, suggesting that clinicians may lack easily accessible data to detect the association between nutrition delivery practices and overall nutrition in infants who are VLBW., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Implications of donor milk feedings on infant growth in resource limited settings remain uncertain. This knowledge gap includes the impact of donor milk availability on infant intake of mother's own milk. Therefore, this investigation aimed to measure intake and growth in infants receiving donor milk when born to women from resource limited backgrounds with high rates of human immunodeficiency virus (HIV)., Methods: A retrospective cohort study enrolled eligible infants admitted to a South African combined neonatal intensive and secondary high care unit, within a one year admission period during 2015, with signed consent for donor milk feedings. A certified milk bank provided donor milk. Daily nutritional intake during the first month was recorded. Details included proportional intake of donor milk, mother's own milk and infant formula. The primary outcome of infant growth velocity from day back to birth weight to discharge was calculated when length of stay was ≥14 days. Analyses primarily used T-tests; mixed effects models compared weekly calorie intake., Results: One hundred five infants with donor milk consent were born at 30.9 ± 3.6 weeks of gestation, weighing 1389 ± 708 g. Forty percent of mothers had HIV. Infant growth velocity did not differ based on percent of feedings as donor milk (≥ 50%: 11.8 ± 4.9 g/kg/d; < 50%: 13.5 ± 5.3 g/kg/d; p  = 0.3). Percent of feedings from donor milk was similar based on maternal HIV status (positive: 31 ± 25%; negative: 36 ± 29%; p  = 0.4), as was percent of feedings as mother's milk (positive: 53 ± 35%; negative: 58 ± 30%; p  = 0.4). Calorie intake increased markedly during the first two weeks and then plateaued ( p  < 0.0001)., Conclusions: Donor milk feedings in higher proportions did not further impair growth of infants managed in a South African combined neonatal intensive and secondary high care unit with growth rates already below reference ranges. The provision of donor milk contributed to feedings being composed of primarily human milk during the first month. Increasing early calorie intake may improve infant growth in this center., Competing Interests: The Human Research Ethics Committees for the University of Cape Town and Mowbray Maternity Hospital approved this human subject research (#236/2016). A waiver of consent was provided for this retrospective study.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Very low birth weight (VLBW) infants remain at risk for postnatal growth restriction. Clinicians may have difficulty identifying growth patterns resulting from nutrition interventions, impeding prompt management changes intended to increase growth velocity. This study aimed to quantify the association between growth and nutrition intake through 7-day moving averages (SDMAs)., Methods: The first 6 weeks of daily nutrition intake and growth measurements were collected from VLBW infants admitted to a level 4 neonatal intensive care unit (2011-2014). The association between SDMA for energy and macronutrients and subsequent 7-day growth velocities for weight, length, and head circumference were determined using mixed effects linear regression. Analyses were adjusted for fluid intake, infant characteristics, and comorbid conditions., Results: Detailed enteral and parenteral caloric provisions were ascertained for 115 infants (n = 4643 patient-days). Each 10-kcal/kg/d increase over 7 days was independently associated with increased weight (1.7 g/kg/d), length (0.4 mm/wk), and head circumference (0.9 mm/wk; P < .001, for weight and head circumference; P = .041 for length). Each 1 g/kg/d macronutrient increase was also associated with increased weight (protein, P = .027; fat and carbohydrates, P < .001), increased length (fat, P = .032), and increased head circumference (fat and carbohydrates, P < .001)., Conclusions: The SDMA identifies clinically meaningful associations among total energy, macronutrient dosing, and growth in VLBW infants. Whether SDMA is a clinically useful tool for providing clinicians with prompt feedback to improve growth warrants further attention., (© 2017 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: In some studies, the dose of intravenous soybean oil (SO) has been associated with a decreased incidence of intestinal failure-associated liver disease. The effect of lipid sparing on neurodevelopment (ND) and growth remains unknown. This study investigated the impact of SO dose on ND and growth over the first 2 years of age in preterm neonates., Materials and Methods: This is a single-site prospective follow-up study. Neonates with a gestational age ≤29 weeks were randomized to low-dose (LOW) or standard-dose (CON) SO. Bayley Scales of Infant Development III and anthropometric measurements were collected at approximately 6, 12, and 24 months corrected gestational age., Results: Subjects were premature, with a mean (±SD) gestational age of 28 ± 1 and 27 ± 1 weeks (P = .3) for LOW and CON, respectively. Thirty subjects completed follow-up (LOW = 15, CON = 15). There were no differences for ND and growth outcomes when LOW was compared with CON, with the exception of a higher 12-month follow-up cognitive scaled score in the LOW group (P = .02)., Conclusion: A reduced SO dose did not adversely affect ND or growth in this cohort of preterm neonates. However, larger studies are needed to determine the long-term safety of SO dose reduction before this strategy can be adopted., (© 2016 American Society for Parenteral and Enteral Nutrition.)

The ability to hold a pace is a key skill for endurance athletes. The present study compared the influence of different strategies on how athletes learn to pace at 80% of their maximum performance for a 3-min cycle time trial. Participants first completed three maximal 3-min tests to establish maximal performance. During subsequent visits we asked participants to ride at 80% of their average maximal 3-min power output for four 3-min efforts under different conditions. Participants were blinded to feedback for three of the four conditions with participants (a) riding on feel (all feedback blinded), (b) associating on the task by focusing attention on the skills needed for efficient cycling, and (c) dissociating from the task by intentionally focusing concentration elsewhere (d) and finally, participants rode with full feedback where pace could be regulated via observation. All participants completed the blind condition first, the full feedback condition last, with association focus and dissociation focus rides being alternated. As expected, results showed participants rode close to the 80% goal when observing full feedback. Participants rode at 82% of maximum in the blind "ride on feel" condition, 79% in the associative condition, and 70% in the dissociative condition. We suggest results show that simple strategies related to concentration can influence the accuracy of pacing efforts. The difference in the ability to pace while using an associative or dissociative attentional focus was consistent with theory. The differences we observed occurred with minimal input from participants in terms of actively learning psychological skills. Future research is needed to investigate how athletes learn to use pacing strategies to help performance., (© 2018 Elsevier B.V. All rights reserved.)

Objective: The aim of the study was to describe the nutritional provisions received by infants with surgical necrotizing enterocolitis (NEC) and the associated effects on short-term growth., Methods: Through the Children's Hospitals Neonatal Database, we identified infants born ≤32 weeks' gestation with surgical NEC from 5 regional neonatal intensive care units for 4 years. Excluded infants had isolated intestinal perforation and died <14 days postoperatively. Infants were stratified by their median parenteral protein dose (low [LP] or high [HP] protein) for the first postoperative week. The primary outcome was postoperative weight growth velocity. Growth (weight, length, and head circumference [HC]) was measured and the effects related to protein dose were estimated using multivariable analyses., Results: There were 103 infants included; the median parenteral protein dose received was 3.27 g · kg · day (LP: 2.80 g · kg · day; HP: 3.87 g · kg · day). Postoperative weight (11.5 ± 6.5 g · kg · day) and linear growth (0.9 ± 0.2 cm/wk) were similar regardless of dose (P > 0.3 between groups for weight and length). Unadjusted and independent associations were identified with HC changes and HP dose (β = 0.1 cm/wk, P = 0.03) after adjusting for gestational age, the presence of severe bronchopulmonary dysplasia, short bowel syndrome, blood stream infection, severe intraventricular hemorrhage, small for gestational age, and calorie intake. Eventual nonsurvivors received 18% less protein and 14% fewer calories over the first postoperative month., Conclusions: Postoperative protein doses in infants with surgical NEC appear related to increases in HC. The influence of postoperative nutritional support on risk of adverse outcomes deserves further attention.

This study aimed to measure longitudinal quantities of the long chain fatty acids, their biologically active terminal metabolites and related intermediates (also called oxylipins) in preterm human milk expressed during the first month of lactation. In a prospective cohort, breast milk was collected throughout the first month of lactation in 30 women who delivered preterm infants. Eighteen bioactive lipids and their intermediates were quantified via solid phase extraction and LC-MS/MS. Analysis by GC-FID quantified the fatty acid precursors. Arachidonic acid (ARA) and docosahexaenoic acid (DHA) milk concentrations significantly declined throughout the first month. Oxylipin concentrations did not change during lactation. Positive associations existed between ARA and thromboxane B2, eicosapentaenoic acid and 18-hydroxyeicosapentaenoic acid, and between DHA and PDX and 14- and 17-hydroxydocosahexaenoic acids. DHA concentrations were 1.5 times higher and 14-HDHA was 1.7 times higher in milk from women taking DHA supplements. This investigation showed conditionally essential fatty acids, ARA and DHA, decreased in preterm milk, suggesting a need to supplement their intake for the breast milk-fed preterm infant. Positive associations between parent fatty acids, bioactive lipids and intermediates, as well as sensitivity of milk to maternal fatty acid intake, support consideration of a comprehensive approach to providing fatty acids for preterm infants through both maternal and infant supplementation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Parenteral nutrition (PN) represents one of the most notable achievements of modern medicine, serving as a therapeutic modality for all age groups across the healthcare continuum. PN offers a life-sustaining option when intestinal failure prevents adequate oral or enteral nutrition. However, providing nutrients by vein is an expensive form of nutrition support, and serious adverse events can occur. In an effort to provide clinical guidance regarding PN therapy, the Board of Directors of the American Society for Parenteral and Enteral Nutrition (ASPEN) convened a task force to develop consensus recommendations regarding appropriate PN use. The recommendations contained in this document aim to delineate appropriate PN use and promote clinical benefits while minimizing the risks associated with the therapy. These consensus recommendations build on previous ASPEN clinical guidelines and consensus recommendations for PN safety. They are intended to guide evidence-based decisions regarding appropriate PN use for organizations and individual professionals, including physicians, nurses, dietitians, pharmacists, and other clinicians involved in providing PN. They not only support decisions related to initiating and managing PN but also serve as a guide for developing quality monitoring tools for PN and for identifying areas for further research. Finally, the recommendations contained within the document are also designed to inform decisions made by additional stakeholders, such as policy makers and third-party payers, by providing current perspectives regarding the use of PN in a variety of healthcare settings.

Fatty acids are critical nutrient regulators of intracellular signaling and influence key pathways including inflammatory responses, hemostasis as well as central nervous system development and function. Preterm birth interrupts the maternal-fetal transfer of essential fatty acids including docosahexaenoic and arachidonic acids, which occurs during the third trimester. Postnatal deficits of these nutrients accrue in preterm infants during the first week and they remain throughout the first months. Due to the regulatory roles of these fatty acids, such deficits contribute an increased risk of developing prematurity-related morbidities including impaired growth and neurodevelopment. The fatty acid contents of parenteral and enteral nutrition are insufficient to meet current recommendations. This chapter summarizes the regulatory roles of fatty acids, current recommendations and limitations of parenteral and enteral nutrition in meeting these recommendations in preterm infants. Suggested areas for research on the roles of fatty acids in preterm infant health are also provided., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective  To estimate associations of exclusive human milk (EHM) feedings with growth and neurodevelopment through 18 months corrected age (CA) in extremely low birth weight (ELBW) infants. Study Design  ELBW infants admitted from July 2011 to June 2013 who survived were reviewed. Infants managed from July 2011 to June 2012 were fed with bovine milk-based fortifiers and formula (BOV). Beginning in July 2012, initial feedings used a human milk-based fortifier to provide EHM feedings. Infants were grouped on the basis of feeding regimen. Primary outcomes were the Bayley-III cognitive scores at 6, 12, and 18 months and growth. Results  Infants ( n  = 85; 46% received EHM) were born at 26 ± 1.9 weeks ( p  = 0.92 between groups) weighing 776 ± 139 g ( p  = 0.67 between groups). Cognitive domain scores were similar at 6 months (BOV: 96 ± 7; EHM: 95 ± 14; p  = 0.70), 12 months (BOV: 97 ± 10; EHM: 98 ± 9; p  = 0.86), and 18 months (BOV: 97 ± 16; EHM: 98 ± 14; p  = 0.71) CA. Growth velocity prior to discharge (BOV: 12.1 ± 5.2 g/kg/day; EHM: 13.1 ± 4.0 g/kg/day; p  = 0.33) and subsequent growth was similar between groups. Conclusion  EHM feedings appear to support similar growth and neurodevelopment in ELBW infants as compared with feedings containing primarily bovine milk-based products., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Extremely-low-birth-weight (ELBW) infants accrue large deficits in docosahexaenoic acid (DHA) and arachidonic acid (ARA) and require improved supplementation strategies. We hypothesized that once daily DHA+ARA drops applied to buccal mucosa will increase blood levels., Methods: Thirty ELBW infants were randomized to receive DHA 20 mg/kg/d + ARA 40 or 60 mg/kg/d + ARA 120 mg/kg/d or placebo within 72 h of age for 8 wk duration. Red blood cell phospholipid levels of DHA (primary) and ARA (secondary) were measured at 2 and 8 wk of age., Results: Twenty-eight survivors with a median birth weight of 806 g completed dosing and sampling. Red blood cell levels were similar between the three groups at 2 wk (DHA: 4.62 wt% (interquartile range (IQR) 4.1-5.5) for all, P = 0.29 between groups; ARA: 21.1 wt% (IQR 18.78-22.6) for all, P = 0.41 between groups) and 8 wk (DHA: 6.0 wt% (IQR 5.1-7.1) for all, P = 0.57 between groups; ARA: 20.1 wt% (IQR 18.3-23.1) for all, P = 0.63 between groups). DHA in all infants showed a median increase of 31% from 2 to 8 wk (P < 0.04). ARA levels did not significantly change over time (P > 0.6)., Conclusion: Daily buccal DHA and ARA supplements did not affect fatty acid levels in ELBW infants.

Exurban residential land (one housing unit per 0.2-16.2 ha) is growing in importance as a human-dominated land use. Carbon storage in the soils and vegetation of exurban land is poorly known, as are the effects on C storage of choices made by developers and residents. We studied C storage in exurban yards in southeastern Michigan, USA, across a range of parcel sizes and different types of neighborhoods. We divided each residential parcel into ecological zones (EZ) characterized by vegetation, soil, and human behavior such as mowing, irrigation, and raking. We found a heterogeneous mixture of trees and shrubs, turfgrasses, mulched gardens, old-field vegetation, and impervious surfaces. The most extensive zone type was turfgrass with sparse woody vegetation (mean 26% of parcel area), followed by dense woody vegetation (mean 21% of parcel area). Areas of turfgrass with sparse woody vegetation had trees in larger size classes (> 50 cm dbh) than did areas of dense woody vegetation. Using aerial photointerpretation, we scaled up C storage to neighborhoods. Varying C storage by neighborhood type resulted from differences in impervious area (8-26% of parcel area) and area of dense woody vegetation (11-28%). Averaged and multiplied across areas in differing neighborhood types, exurban residential land contained 5240 ± 865 g C/m 2 in vegetation, highly sensitive to large trees, and 13 800 ± 1290 g C/m 2 in soils (based on a combined sampling and modeling approach). These contents are greater than for agricultural land in the region, but lower than for mature forest stands. Compared with mature forests, exurban land contained more shrubs and less downed woody debris and it had similar tree size-class distributions up to 40 cm dbh but far fewer trees in larger size classes. If the trees continue to grow, exurban residential land could sequester additional C for decades. Patterns and processes of C storage in exurban residential land were driven by land management practices that affect soil and vegetation, reflecting the choices of designers, developers, and residents. This study provides an example of human-mediated C storage in a coupled human-natural system., (© 2016 by the Ecological Society of America.)

Background: Premature infants depend on intravenous fat emulsions to supply essential fatty acids and calories. The dose of soybean-based intravenous fat emulsions (S-IFE) has been associated with parenteral nutrition (PN)-associated liver disease. This study's purpose was to determine if low-dose S-IFE is a safe and effective preventive strategy for cholestasis in preterm neonates., Materials and Methods: This is a multicenter randomized controlled trial in infants with a gestational age (GA) ≤29 weeks. Patients <48 hours of life were randomized to receive a low (1 g/kg/d) or control dose (approximately 3 g/kg/d) of S-IFE. The primary outcome was cholestasis, defined as a direct bilirubin ≥15% of the total bilirubin at 28 days of life (DOL) or full enteral feeds, whichever was later, after 14 days of PN. Secondary outcomes included growth, length of hospital stay, death, and major neonatal morbidities., Results: In total, 136 neonates (67 and 69 in the low and control groups, respectively) were enrolled. Baseline characteristics were similar for the 2 groups. When the low group was compared with the control group, there was no difference in the primary outcome (69% vs 63%; 95% confidence interval, -0.1 to 0.22; P = .45). While the low group received less S-IFE and total calories over time compared with the control group (P < .001 and P = .03, respectively), weight, length, and head circumference at 28 DOL, discharge, and over time were not different (P > .2 for all)., Conclusion: Compared with the control dose, low-dose S-IFE was not associated with a reduction in cholestasis or growth., (© 2014 American Society for Parenteral and Enteral Nutrition.)

The intestinal microbiome is a complex ecosystem of microorganisms that colonize the human gastrointestinal tract. The microbiome evolves rapidly in early life with contributions from diet, genetics and immunomodulatory factors. Changes in composition of the microbiota due to antibiotics may lead to negative long-term effects including obesity and diabetes mellitus, as evidenced by both animal and large human studies. Inappropriate exposures to antibiotics occur frequently in early childhood. Therefore, an evidence-based system of antimicrobial use should be employed by all providers, especially those who care for pediatric patients. This article explores the natural evolution of the intestinal microbiome from the perinatal period into early childhood, the effect of antibiotics on the microbial ecology, and the implications for future health and disease., (Copyright 2015, SLACK Incorporated.)

Systemic administration of small molecule toll-like receptor (TLR)-7 agonists leads to potent activation of innate immunity and to the generation of anti-tumor immune responses. However, activation of TLRs with small molecule agonists may lead to the induction of TLR tolerance, defined as a state of hyporesponsiveness to subsequent agonism, which may limit immune activation, the generation of anti-tumor responses and clinical response. Our data reveal that dose scheduling impacts on the efficacy of systemic therapy with the selective TLR7 agonist, 6-amino-2-(butylamino)-9-((6-(2-(dimethylamino)ethoxy)pyridin-3-yl)methyl)-7,9-dihydro-8H-purin-8-one (DSR-6434). In a preclinical model of renal cell cancer, systemic administration of DSR-6434 dosed once weekly resulted in a significant anti-tumor response. However, twice weekly dosing of DSR-6434 led to the induction of TLR tolerance, and no anti-tumor response was observed. We show that TLR7 tolerance was independent of type I interferon (IFN) negative feedback because induction of TLR7 tolerance was also observed in IFN-α/β receptor knockout mice treated with DSR-6434. Moreover, our data demonstrate that treatment of bone marrow-derived plasmacytoid dendritic cells (BM-pDC) with DSR-6434 led to downregulation of TLR7 expression. From our data, dose scheduling of systemically administered TLR7 agonists can impact on anti-tumor activity through the induction of TLR tolerance. Furthermore, TLR7 expression on pDC may be a useful biomarker of TLR7 tolerance and aid in the optimization of dosing schedules involving systemically administered TLR7 agonists.

Components of diet, including the total amounts and specific types of fat, affect the composition of the intestinal microbiome in both animal models and cohort studies of humans. Amounts of total fat and specific fatty acids (FA) are some of the most variable nutritional components of breast milk. Evaluations of the microbiome in premature infants have shown decreased diversity of species and increased proportions of potentially pathogenic bacteria. Microbial patterns in premature infants may be affected by nutritional fat intake, altering risk of diseases such as necrotizing enterocolitis. Dietary FA may also impact disease susceptibility through molecular mechanisms. Specifically, intestinal Toll-like receptor 4 expression is altered by manipulation of FA in murine models. Abnormal increased expression of Toll-like receptor 4, the receptor for lipopolysaccharide, has been implicated in necrotizing enterocolitis. This report will review the role of dietary fat in the composition of the intestinal microbiome, the extreme variability of FA intake in premature infants, and associations of both dysbiosis and FA intake with the development of necrotizing enterocolitis.

Objective: The aim of this study is to assess the influence of parenteral nutrition (PN) on the time to regain birth weight in premature neonates born between 1,500 and 2,499 g., Study Design: A retrospective analysis stratified premature neonates born between 1,500 and 2,499 g by receipt of PN or intravenous dextrose at ≤ 72 hours of age. The primary outcome was the time to regain birth weight. Secondary measures included preterm-associated morbidities, time to achieve predefined enteral nutrition milestones, and length of stay. Multivariable regression estimated associations between PN and time to achieve nutrition milestones., Results: Among 260 eligible neonates, those receiving PN (53%) were less mature, weighed less at birth, had a higher index of illness severity, and higher prevalence of preterm-associated morbidities (p < 0.01). The time to regain birth weight (PN, 9.4 ± 3.5 d; no PN, 9.5 ± 3.4 d) was similar between groups. Regression analysis adjusting for gestational age, illness severity, and sepsis demonstrated that PN exposure was associated with a greater time to achieve nutrition milestones and length of stay (p < 0.05)., Conclusion: Although its impact on growth remains uncertain among premature neonates born between 1,500 and 2,499 g, PN was independently associated with a greater time to achieve nutrition milestones., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Although topical TLR7 therapies such as imiquimod have proved successful in the treatment of dermatological malignancy, systemic delivery may be required for optimal immunotherapy of nondermatological tumors. We report that intravenous delivery of the novel small molecule TLR7 agonist, DSR-6434, leads to the induction of type 1 interferon and activation of T and B lymphocytes, NK and NKT cells. Our data demonstrate that systemic administration of DSR-6434 enhances the efficacy of ionizing radiation (IR) and leads to improved survival in mice bearing either CT26 or KHT tumors. Of the CT26 tumor-bearing mice that received combined therapy, 55% experienced complete tumor resolution. Our data reveal that these long-term surviving mice have a significantly greater frequency of tumor antigen specific CD8(+) T cells when compared to age-matched tumor-naïve cells. To evaluate therapeutic effects on spontaneous metastases, we showed that combination of DSR-6434 with local IR of the primary tumor significantly reduced metastatic burden in the lung, when compared to time-matched cohorts treated with IR alone. The data demonstrate that systemic administration of the novel TLR7 agonist DSR-6434 in combination with IR primes an antitumor CD8(+) T-cell response leading to improved survival in syngeneic models of colorectal carcinoma and fibrosarcoma. Importantly, efficacy extends to sites outside of the field of irradiation, reducing metastatic load. Clinical evaluation of systemic TLR7 therapy in combination with IR for the treatment of solid malignancy is warranted., (© 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.)