Use of technology in neonatal nutrition.

There have been rapidly expanding uses of technology to enhance and improve nutrition in our smallest patients. Optimized nutrition in the neonatal patient is linked to improved outcomes, specifically neurodevelopmental outcomes and decreased length of stay. Despite advances in neonatal care that have improved survival, many patients being discharged from the neonatal intensive care unit are doing so with poor postnatal growth. Because the neonatal brain doubles in size from 20 weeks gestation to term, it is essential to focus care efforts on nutrition to optimize brain growth and development. This review focuses on three exciting areas of neonatal research, including the analysis of macronutrients in breast milk, measurement of body composition, and use of telemedicine.

Neonatal hypoglycemia algorithms improve hospital outcomes.

OBJECTIVE: Neonatal hypoglycemia is a common diagnosis for which management strategies vary. Our goal was to implement hypoglycemia algorithms (HGA) to streamline management of neonatal hypoglycemia within our hospital system and improve outcomes related to promoting the mother-infant dyad and decreasing hospital costs. PATIENTS AND METHODS: A retrospective cohort study analyzed data on 4,666 asymptomatic infants at risk for hypoglycemia and born at two, large, community hospitals between 2010 and 2016. The first algorithm (HGA1) was created in 2012 and subsequently updated (HGA2) in 2014 to include the use of dextrose gel. Infants were separated into three groups by epoch: pre-HGA (2010-2011), HGA1 (2012-2013), and HGA2 (2014-2016). Outcomes between groups were then analyzed. Cost savings were calculated using linear regression. RESULTS: Compared with the pre-HGA group, the HGA1 group had decreased intravenous dextrose use (3.9 vs. 2.5%, p < .001). Compared with the HGA1 group, the HGA2 group had decreased intravenous dextrose use (2.5 vs. 1.0%, p < .001) and increased breastfeeding rates (88.4% vs. 86.7%, p = .003). Neonatal intensive care unit admission rates decreased when comparing the pre-HGA group with the HGA2 group (10.6% vs 9.4%, p = .03). Length of stay was overall unchanged. Total cost savings were approximately $222 per case. CONCLUSIONS: By implementing HGA1 and providing resources to unify care for asymptomatic infants at risk for hypoglycemia, short-term outcomes in our hospital system improved. By updating HGA2 to include the use of dextrose gel, the advantages gained by HGA1 were maintained and further enhanced. Overall cost of care was reduced.

Body composition and cognition in preschool-age children with congenital gastrointestinal anomalies.

BACKGROUND: Children with congenital gastrointestinal anomalies (CGIAs) experience multiple stressors while hospitalized in neonatal intensive care units during an essential time of growth and development. Early stress and inadequate nutrition are linked to altered growth patterns and later neurodevelopmental delays. In other at-risk populations, improved fat-free mass (FFM) accretion is associated with improved cognitive outcomes. OBJECTIVE: To determine if body composition is associated with cognitive function in preschool-age children with CGIAs. STUDY DESIGN: An observational study examined body composition and cognition in 34 preschool-age children with CGIAs. Anthropometric measurements and body composition testing via air displacement plethysmography were obtained. Measurements were compared with a reference group of healthy, term-born children. Cognition was measured with the NIH Toolbox Early Childhood Cognition Battery. Linear regression was used to test the association of body composition with cognitive function. RESULTS: Compared with the reference group, children with CGIAs had similar anthropometric measurements (weight, height, and body mass index z-scores) and body composition at preschool-age. Processing speed scores were lower than standardized means (p = 0.001). Increased FFM was associated with higher receptive vocabulary scores (p = 0.001), cognitive flexibility scores (p = 0.005), and general cognitive function scores (p = 0.05). CONCLUSIONS: At preschool-age, children with CGIAs have similar growth and body composition to their peers. In children with CGIAs, higher FFM was associated with higher cognitive scores. Closer tracking of body composition and interventions aimed at increasing FFM may improve long-term outcomes in this population.

Body Composition Changes from Infancy to 4 Years and Associations with Early Childhood Cognition in Preterm and Full-Term Children.

BACKGROUND: Infants born prematurely are at risk for neurodevelopmental complications. Early growth is associated with improved later cognition. The relationship of early proportionality and body composition with later cognition is not well established. OBJECTIVES: To assess differences in fat-free mass and adiposity (fat mass, percent body fat) changes in preterm and full-term infants through preschool age and examine associations with early childhood cognition. METHODS: This is a prospective, observational study in an appropriate for gestational age cohort of 71 patients (20 preterm and 51 full-term) from infancy through preschool age. Anthropometric and body composition measurements via air displacement plethysmography were obtained during infancy at term and 3-4 months (preterm corrected ages), and at 4 years. Cognitive testing occurred at 4 years. Associations of body composition changes between visits with cognitive function were tested using linear regression. RESULTS: In the preterm group, higher term to 4-month corrected age percent body fat gains were associated with lower working memory performance (p = 0.01), and higher 4-month corrected age to 4-year fat-free mass gains were associated with higher full-scale IQ (p = 0.03) and speed of processing performance (p ≤ 0.02). In the full-term group, higher 4-month to 4-year fat mass gains were associated with lower full-scale IQ (p = 0.03). CONCLUSIONS: Body composition gains during different time periods are associated with varying areas of cognitive function. These findings may inform interventions aimed at optimal growth.

Myostatin signals through Pax7 to regulate satellite cell self-renewal.

Myostatin, a Transforming Growth Factor-beta (TGF-beta) super-family member, has previously been shown to negatively regulate satellite cell activation and self-renewal. However, to date the mechanism behind Myostatin function in satellite cell biology is not known. Here we show that Myostatin signals via a Pax7-dependent mechanism to regulate satellite cell self-renewal. While excess Myostatin inhibited Pax7 expression via ERK1/2 signaling, an increase in Pax7 expression was observed following both genetic inactivation and functional antagonism of Myostatin. As a result, we show that either blocking or inactivating Myostatin enhances the partitioning of the fusion-incompetent self-renewed satellite cell lineage (high Pax7 expression, low MyoD expression) from the pool of actively proliferating myogenic precursor cells. Consistent with this result, over-expression of Pax7 in C2C12 myogenic cells resulted in increased self-renewal through a mechanism which slowed both myogenic proliferation and differentiation. Taken together, these results suggest that increased expression of Pax7 promotes satellite cell self-renewal, and furthermore Myostatin may control the process of satellite cell self-renewal through regulation of Pax7. Thus we speculate that, in addition to the intrinsic factors (such as Pax7), extrinsic factors both positive and negative in nature, will play a major role in determining the stemness of skeletal muscle satellite cells.

Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF-kappaB-independent, FoxO1-dependent mechanism.

Myostatin, a transforming growth factor-beta (TGF-beta) super-family member, has been well characterized as a negative regulator of muscle growth and development. Myostatin has been implicated in several forms of muscle wasting including the severe cachexia observed as a result of conditions such as AIDS and liver cirrhosis. Here we show that Myostatin induces cachexia by a mechanism independent of NF-kappaB. Myostatin treatment resulted in a reduction in both myotube number and size in vitro, as well as a loss in body mass in vivo. Furthermore, the expression of the myogenic genes myoD and pax3 was reduced, while NF-kappaB (the p65 subunit) localization and expression remained unchanged. In addition, promoter analysis has confirmed Myostatin inhibition of myoD and pax3. An increase in the expression of genes involved in ubiquitin-mediated proteolysis is observed during many forms of muscle wasting. Hence we analyzed the effect of Myostatin treatment on proteolytic gene expression. The ubiquitin associated genes atrogin-1, MuRF-1, and E214k were upregulated following Myostatin treatment. We analyzed how Myostatin may be signaling to induce cachexia. Myostatin signaling reversed the IGF-1/PI3K/AKT hypertrophy pathway by inhibiting AKT phosphorylation thereby increasing the levels of active FoxO1, allowing for increased expression of atrophy-related genes. Therefore, our results suggest that Myostatin induces cachexia through an NF-kappaB-independent mechanism. Furthermore, increased Myostatin levels appear to antagonize hypertrophy signaling through regulation of the AKT-FoxO1 pathway.

Proteolytic processing of myostatin is auto-regulated during myogenesis.

Myostatin, a potent negative regulator of myogenesis, is proteolytically processed by furin proteases into active mature myostatin before secretion from myoblasts. Here, we show that mature myostatin auto-regulates its processing during myogenesis. In a cell culture model of myogenesis, Northern blot analysis revealed no appreciable change in myostatin mRNA levels between proliferating myoblasts and differentiated myotubes. However, Western blot analysis confirmed a relative reduction in myostatin processing and secretion by differentiated myotubes as compared to proliferating myoblasts. Furthermore, in vivo results demonstrate a lower level of myostatin processing during fetal muscle development when compared to postnatal adult muscle. Consequently, high levels of circulatory mature myostatin were detected in postnatal serum, while fetal circulatory myostatin levels were undetectable. Since Furin proteases are important for proteolytically processing members of the TGF-beta superfamily, we therefore investigated the ability of myostatin to control the transcription of furin and auto-regulate the extent of its processing. Transfection experiments indicate that mature myostatin indeed regulates furin protease promoter activity. Based on these results, we propose a mechanism whereby myostatin negatively regulates its proteolytic processing during fetal development, ultimately facilitating the differentiation of myoblasts by controlling both furin protease gene expression and subsequent active concentrations of mature myostatin peptide.