Human Milk Oligosaccharides, Growth, and Body Composition in Very Preterm Infants.

Human milk oligosaccharides (HMOs) are bioactive factors that benefit neonatal health, but little is known about effects on growth in very preterm infants (<32 weeks' gestation). We aimed to quantify HMO concentrations in human milk fed to very preterm infants during the neonatal hospitalization and investigate associations of HMOs with infant size and body composition at term-equivalent age. In 82 human-milk-fed very preterm infants, we measured HMO concentrations at two time points. We measured anthropometrics and body composition with air displacement plethysmography at term-equivalent age. We calculated means of individual and total HMOs, constructed tertiles of mean HMO concentrations, and assessed differences in outcomes comparing infants in the highest and intermediate tertiles with the lowest tertile using linear mixed effects models, adjusted for potential confounders. The mean (SD) infant gestational age was 28.2 (2.2) weeks, and birthweight was 1063 (386) grams. Exposure to the highest (vs. lowest) tertile of HMO concentrations was not associated with anthropometric or body composition z-scores at term-corrected age. Exposure to the intermediate (vs. lowest) tertile of 3FL was associated with a greater head circumference z-score (0.61, 95% CI 0.15, 1.07). Overall, the results do not support that higher HMO intakes influence growth outcomes in this very preterm cohort.

Human Milk Oligosaccharides and Infant Neurodevelopment: A Narrative Review.

The objective of this narrative review was to synthesize the literature on human milk oligosaccharides (HMOs) and neurodevelopmental outcomes in human milk-fed infants. We conducted a scoping review of the literature indexed in PubMed reporting observational or interventional studies on HMO exposure in relation to psychometric measures in infants. Studies were characterized based on study design and definitions of HMO exposure and neurodevelopmental outcomes. Six studies were identified; all were observational in design, and five were conducted in full-term infants. Sample sizes ranged from 35-659 infants. HMOs were defined as individual concentrations or relative abundances assessed at 1 and/or 6 months of age. Studies accounted for differences in HMO exposure based on maternal secretor status. Neurodevelopmental outcomes were assessed between 6 and 24 months of age and included four domains. Studies in full-term infants reported that total and individual fucosylated and sialylated HMOs were positively associated with cognitive, language, and motor skill domains between 18 and 24 months of age, while the single study in preterm infants reported no statistically significant findings in the full cohort. The presence of a maternal secretor did not consistently alter the associations between HMO exposure and neurodevelopmental outcomes. Emerging evidence from observational studies suggests that HMO exposure may be beneficial for neurodevelopment in infants.

Preterm infant nutrition and growth with a human milk diet.

Human milk is the preferred enteral diet for preterm infants. It provides macronutrients, micronutrients, and bioactive factors that support physical growth and neurodevelopment. Challenges of the human milk diet include the variability in its composition and a need for fortification to mirror placental nutrient delivery and prevent extrauterine growth restriction. Various strategies exist to attain target nutrient provision and optimize growth, including leveraging new technology for point-of-care human milk analysis. When maternal milk is unavailable or in short supply, pasteurized donor human milk is the preferred alternative. Infants fed donor milk may have slower weight gain than those fed exclusively maternal milk or formula, whereas infants fed fortified maternal milk have similar weight gain to preterm formula-fed infants. Future directions include more rigorous characterization of the variation in human milk, further investigation of the clinical benefits of non-nutrient bioactive factors in milk, and novel approaches to optimize fortification.

Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease.

BACKGROUND: Intravenous fish oil (FO) treats pediatric intestinal failure-associated liver disease (IFALD). There are concerns that a lipid emulsion composed of ω-3 fatty acids will cause an essential fatty acid deficiency (EFAD). This study's objective was to quantify the risk for abnormal fatty acid concentrations in children treated with FO. METHODS: Inclusion criteria for this prospective study were children with intestinal failure. Intravenous soybean oil (SO) was replaced with FO for no longer than 6 months. Serum fatty acids were analyzed using linear and logistic models, and compared with age-based norms to determine the percentage of subjects with low and high concentrations. RESULTS: Subjects (n = 17) started receiving FO at a median of 3.6 months (interquartile range 2.4-9.6 months). Over time, α-linolenic, linoleic, arachidonic, and Mead acid decreased, whereas docosahexaenoic and eicosapentaenoic acid increased (P < 0.001 for all). Triene-tetraene ratios remained unchanged (P = 1). Although subjects were 1.8 times more likely to develop a low linoleic acid while receiving FO vs SO (95% CI: 1.4-2.3, P < 0.01), there was not a significant risk for low arachidonic acid. Subjects were 1.6 times more likely to develop high docosahexaenoic acid while receiving FO vs SO; however, this was not significant (95% CI: 0.9-2.6, P = 0.08). CONCLUSION: In this cohort of parenteral nutrition-dependent children, switching from SO to FO led to a decrease in essential fatty acid concentrations, but an EFAD was not evident. Low and high levels of fatty acids developed. Further investigation is needed to clarify if this is clinically significant.

Two-Year Neurodevelopment and Growth Outcomes for Preterm Neonates Who Received Low-Dose Intravenous Soybean Oil.

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.

Gonadal- and sex-chromosome-dependent sex differences in the circadian system.

Compelling reasons to study the role of sex in the circadian system include the higher rates of sleep disorders in women than in men and evidence that sex steroids modulate circadian control of locomotor activity. To address the issue of sex differences in the circadian system, we examined daily and circadian rhythms in wheel-running activity, electrical activity within the suprachiasmatic nucleus, and PER2::LUC-driven bioluminescence of gonadally-intact adult male and female C57BL/6J mice. We observed greater precision of activity onset in 12-hour light, 12-hour dark cycle for male mice, longer activity duration in 24 hours of constant darkness for female mice, and phase-delayed PER2::LUC bioluminescence rhythm in female pituitary and liver. Next, in order to investigate whether sex differences in behavior are sex chromosome or gonadal sex dependent, we used the 4 core genotypes (FCG) mouse model, in which sex chromosome complement is independent of gonadal phenotype. Gonadal males had more androgen receptor expression in the suprachiasmatic nucleus and behaviorally reduced photic phase shift response compared with gonadal female FCG mice. Removal of circulating gonadal hormones in adults, to test activational vs organizational effects of sex revealed that XX animals have longer activity duration than XY animals regardless of gonadal phenotype. Additionally, we observed that the activational effects of gonadal hormones were more important for regulating activity levels in gonadal male mice than in gonadal female FCG mice. Taken together, sex differences in the circadian rhythms of activity, neuronal physiology, and gene expression were subtle but provide important clues for understanding the pathophysiology of the circadian system.

Expanding the Grading of Recommendations Assessment, Development, and Evaluation (Ex-GRADE) for Evidence-Based Clinical Recommendations: Validation Study.

Clinicians use general practice guidelines as a source of support for their intervention, but how much confidence should they place on these recommendations? How much confidence should patients place on these recommendations? Various instruments are available to assess the quality of evidence of research, such as the revised Wong scale (R-Wong) which examines the quality of research design, methodology and data analysis, and the revision of the assessment of multiple systematic reviews (R-AMSTAR), which examines the quality of systematic reviews.The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) Working Group developed an instrument called the GRADE system in order to grade the quality of the evidence in studies and to evaluate the strength of recommendation of the intervention that is proposed in the published article. The GRADE looks at four factors to determine the quality of the evidence: study design, study quality, consistency, and directness. After combining the four components and assessing the grade of the evidence, the strength of recommendation of the intervention is established. The GRADE, however, only makes a qualitative assessment of the evidence and does not generate quantifiable data.In this study, we have quantified both the grading of the quality of evidence and also the strength of recommendation of the original GRADE, hence expanding the GRADE. This expansion of the GRADE (Ex-GRADE) permits the creation of a new instrument that can produce tangible data and possibly bridge the gap between evidence-based research and evidence-based clinical practice.

Automatic transport ventilator versus bag valve in the EMS setting: a prospective, randomized trial.

PURPOSE: The primary objective of this study was to compare Emergency Medical Technicians-Paramedics (EMT-P) perceptions of the usefulness of an automatic transport ventilator (ATV) compared with bag valve (BV) ventilation for intubated patients. METHODS: Cardiopulmonary resuscitation or assisted ventilation patients were randomly assigned by day to the ATV or BV arm of the study. Questionnaires were completed by the EMT-Ps at the conclusion of each patient enrollment. EMT-Ps were asked to rate the modality used (ATV versus BV) on ease of use, time of setup, expedition of transport, additional tasks completed, documentation, overall patient care, and patient comfort. RESULTS: Twenty-eight patients were entered into the study, 14 in the BV arm and 14 in the ATV arm. There were significant differences in favor of the ATV in ability to accomplish additional tasks (P = 0.01), ability to document (P = 0.04), and ability to provide patient care (P = 0.03) CONCLUSIONS: EMT-Ps were able to accomplish more tasks, document more completely, and provide better patient care with the use of the ATV.

Effect of a social services intervention among 911 repeat users.

OBJECTIVE: To determine whether emergency medical services (EMS) 911 frequent users would benefit from social services intervention. METHODS: The design was a descriptive prospective subject evaluation. All nonhomeless frequent EMS users (>3x in 1 month) were identified monthly from December 2 to May 3 and contacted by 2 social workers. Information extracted from their contact with the subjects included demographics, ability to enter a social services intervention, and reason for transport. RESULTS: Eighty-four patients were eligible for inclusion in the study. Seventy-four patients were unable to enter a social services intervention for the following reasons: not home (2x) (26%), not at address (19%), refused (13%), unable to complete Mini-Mental Status Exam (10%), deceased (6%), hospitalized (5%), safety issues (4%), and others (10%). The reasons for frequent EMS use were cardiac (24%), asthma/chronic obstructive pulmonary disease (25%), seizures (14%), dialysis problems, alcohol problems, and diabetes-related problems (<10% each). CONCLUSION: Among all patients, the primary reasons for transport were cardiac, asthma/chronic obstructive pulmonary disease, and seizures. Only 12% of patients contacted could enter a social services intervention. On the basis of the small cohort of patients that were able to enter a social services interventions, more targeted interventions are warranted.

Emergency medical services screening of elderly falls in the home.

OBJECTIVES: Previous studies of injury prevention among the elderly have focused on care by community-based services for the elderly. The plan for this study was to determine whether emergency medical services (EMS) could be a valuable partner in an injury prevention program for the elderly. The purposes of the study were: 1) to determine whether it is feasible to gather injury prevention data prospectively, 2) to determine whether these data suggest the need for further intervention to aid the elderly, and 3) to determine whether retrospective chart data are comparable to prospectively gathered data for evaluating the elderly home environment. METHODS: Trained fire/EMS chiefs gathered prospective data from the homes of all elderly falls. Patients were included if they were 65 years of age or older. Demographics extracted from the chart were gender, age, and average income based on zip code information from the city office. A 29-question survey was developed based on a literature review. Results were obtained representing information in six categories: environment, appearance, health, violence, access to help, and repeat medical care utilization. Retrospective data were obtained from run reports and from a computerized EMS database. Proportions and 95% confidence intervals were used. A p-value < 0.05 was considered statistically significant. RESULTS: There were 70 prospective elderly fall cases evaluated and 74 retrospective charts reviewed, each representing a two-to-four-month period. Prospectively, significant problems were found with the patient's environment in up to 53% of cases, appearance in up to 29%, health in up to 77%, abuse in up to 3%, access in up to 57%, and repeat use in 33-68%. Although there were no differences in the age, income, or percentage transported between the prospective and retrospectively obtained groups, a significantly higher percentage of females were entered prospectively. Retrospective chart review obtained reasonable amounts of data for only four of 29 questions. CONCLUSION: Prospective analysis is easily gathered and identifies elderly injuries and patterns. A significant number of elderly patients whose homes were visited by EMS need help. Retrospective analysis gleans little injury prevention information.