Enteral long-chain polyunsaturated fatty acids and necrotizing enterocolitis: A systematic review and meta-analysis.

BACKGROUND: Preterm infants are at risk of long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Recent studies on high-dose DHA; n-3 LCPUFA in preterm infants suggested potential positive effects on cognitive outcomes but raised concerns about some increased neonatal morbidities. These studies and recent recommendations for DHA supplementation generated controversy owing to the lack of balance between DHA and arachidonic acid (ARA; n-6 LCPUFA). OBJECTIVES: To identify the effect of enteral supplementation of DHA, with and without ARA, on necrotizing enterocolitis (NEC) in very preterm infants. METHODS: A systematic review of randomized and controlled trials compared enteral LCPUFAs with placebo or no supplementation in very preterm infants. We searched PubMed, Ovid-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINHAL databases from inception to July 2022. Data were extracted in duplicate using a structured proforma. A meta-analysis and metaregression with random-effects models were used. The interventions evaluated were DHA alone vs. that combined with ARA, source of DHA, dose, and supplement delivery methods. Methodological qualities and risk of bias were assessed using the Cochrane risk-of-bias tool. RESULTS: Fifteen randomized clinical trials (RCTs) included 3963 very preterm infants with 217 cases of NEC. Supplementation with DHA alone increased NEC (2620 infants; RR: 1.56; 95% CI: 1.02, 2.39) with no evidence of heterogeneity (I2 = 0.0%, P = 0.46). Multiple metaregression revealed significant reduction in NEC when ARA was supplemented with DHA (aRR 0.42; 95% CI: 0.21, 0.88). The source of DHA, dose, and feeding type revealed no associations with NEC. Two RCTs supplemented high-dose DHA to lactating mothers. There was a significant increase in risk of NEC with this approach (1148 infants; RR: 1.92; 95% CI: 1.02, 3.61) with no evidence of heterogeneity (I2 = 0.0, P = 0.81). CONCLUSIONS: Supplementation with DHA alone may increase risk of NEC. Concurrent supplementation with ARA needs to be considered when adding DHA to preterm infants' diet.

Effect of Enteral Protein Amount on Growth and Health Outcomes in Very-Low-Birth-Weight Preterm Infants: Phase II of the Pre-B Project and an Evidence Analysis Center Systematic Review.

Adequate protein intake by very-low-birth-weight preterm infants (≤1,500 g at birth) is essential to optimize growth and development. The estimated needs for this population are the highest of all humans, however, the recommended intake has varied greatly over the past several years. A literature search was conducted in PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases to identify randomized controlled trials evaluating the effect of prescribed protein intake and identified outcomes. Articles were screened by 2 reviewers, risk of bias was assessed, data were synthesized quantitatively and narratively, and each outcome was separately graded for certainty of evidence. The literature search retrieved 25,384 articles and 2 trials were included in final analysis. No trials were identified that evaluated effect of protein amount on morbidities or mortality. Moderate certainty evidence found a significant difference in weight gain when protein intake of greater than 3.5 g/kg/day from preterm infant formula was compared with lower intakes. Low-certainty evidence found no evidence of effect of protein intake of 2.6 vs 3.1 vs 3.8 g/kg/day on length, head circumference, skinfold measurements, or mid-arm circumference. Low-certainty evidence found some improvement in development measures when higher protein intake of 3.8 vs 3.1 vs 2.6 g/kg/day were compared. Low-certainty evidence found no significant difference in bone mineral content when these protein intakes were compared. No studies were identified that compared protein intake greater than 4.0 g/kg/day. This systematic review found that protein intake between 3.5 and 4.0 g/kg/day promotes weight gain and improved development.

Nutrition interventions in populations with mental health conditions: a scoping review.

Nutrition is a modifiable factor for intervention in mental disorders. This scoping review characterized nutrition intervention research in mental disorders. A 3-category framework characterized nutrition interventions: Guide (e.g., counselling), Provide (e.g., food provisions), and Add (e.g., supplementation). Nutrition interventions were classified as single-component (e.g., Guide) or complex (e.g., Guide-Provide). Sixty-nine trials met inclusion criteria, 96% were randomized controlled trials. Most commonly diagnosed mental disorders were depressive disorder (i.e., persistent) or major depressive disorder (n = 39), schizophrenia (n = 17), and other psychotic disorders (n = 13). Few trials included patients with anxiety disorders (n = 2) or bipolar disorders (n = 3). Several trials (n = 15, 22%) assessed and implemented nutrition interventions to improve dietary patterns, of which 11 (73%) reported statistically significant and clinically important positive effects of nutrition interventions on mental disorders. The majority of the trials (n = 61, 90%) investigated supplementation, most commonly adding essential fatty acids, vitamins, or minerals. The majority (n = 48, 70%) reported either statistically significant or clinically important effect and 31 (51%) reported both. Though most interventions led to statistically significant improvements, trials were heterogeneous for targeted mental disorders, nutrition interventions, and outcomes assessed. Given considerable heterogeneity, further research from robust and clinically relevant trials is required to support high-quality health care with effective nutrition interventions. Novelty Future research on whole-diet interventions powered to detect changes in mental health outcomes as primary objectives is needed. Dietitians may be an opportunity to improve feasibility and efficacy of nutrition interventions for mental disorder patients. Dietitians may be of value to educate mental health practitioners on the importance of nutrition.

Carnitine Profile Changes in Pediatric Hematopoietic Stem Cell Transplant: New Role for Carnitine?

Carnitine is an essential cofactor for mitochondrial import and oxidation of fatty acids. High-dose chemotherapy and radiation, often required for hematopoietic stem cell transplant (HSCT), leads to tissue damage, mitochondrial dysfunction, and alterations in carnitine metabolism. The aim of this pilot cohort study was to describe plasma and urinary carnitine profiles during pediatric HSCT and their relationships with clinical outcomes. Plasma and urinary carnitine samples were collected from 22 pediatric patients before and through day 180 post-HSCT. Associations were observed between graft-versus-host disease and an elevated plasma total carnitine (P=0.019), and also increased plasma acyl:free carnitine ratio with veno-occlusive disease (P=0.016). Mortality was observed in those with their highest urinary total carnitine losses on day 0 (P=0.005), and in those with an abnormal day 28 plasma ratio either above or below the reference range (P=0.007). Changes in carnitine profiles were more reflective of metabolic stress and negative outcomes than of inadequate dietary intake. Associations observed direct larger studies to assess the validity of carnitine profiles as a prognostic indicator and also to assess whether prophylactic carnitine supplementation pre-HSCT could reduce mitochondrial injury and urinary losses and help mitigate inflammatory and metabolic comorbidities of HSCT.

Iron requirements in the first 2 years of life.

Iron is an essential micronutrient required for hemoglobin synthesis, central nervous system development, and protection from infection. Early childhood is a time of vulnerability as iron deficiency in this period is associated with impaired neurodevelopment. Low socioeconomic status, preterm birth, and suboptimal diet are risk factors for iron deficiency. Due to a lack of iron excretory mechanism, the possibility of iron excess also exists. Appropriate iron intake in the first 2 years of life is critical.

Immunoglobulin A and Protein Content of Low-Fat Human Milk Prepared for the Treatment of Chylothorax.

BACKGROUND: Several case studies report successful recovery from chylothorax while infants were fed low-fat human milk. The reported growth rates were inadequate despite milk supplementation with added medium-chain triglycerides (MCTs). The objective was to determine the effect that various human milk fat separating methods, refrigerated centrifuge, room temperature centrifuge, and refrigeration have on the loss of immunoglobulin A (IgA) and protein in the preparation of low-fat human milk. METHODS: Protein and IgA were measured in 31 samples of reduced-fat human milk. Reduced-fat breastmilk samples were prepared by separating the fat using 3 methods (refrigerated centrifuge, room temperature centrifuge, and a refrigeration method), followed by lower fat milk extraction by syringe. RESULTS: The refrigeration method decreased IgA concentration by 17% (P = .035) while centrifugation and fat removal from the human milk samples led to a 38% decline in IgA concentration in both the nonrefrigerated and refrigerated centrifuge samples (P < .0001 for both). Protein declined by 11% with refrigeration and fat removal (P < .0001) while centrifugation and fat removal decreased protein concentration by 31% (P < .0001) in both nonrefrigerated centrifuge and refrigerated centrifuge samples. CONCLUSIONS: Preparing low-fat human milk for patients with chylothorax decreased the IgA and protein contents. As well as fat (in the form of MCTs), protein likely needs to be supplemented for infants fed low-fat human milk to support adequate growth.

Olive Oil and Soybean Oil Based Intravenous Lipid Emulsions, Liver Biochemistry and Clinical Outcomes.

Intravenous lipid emulsions are an essential component of parenteral nutrition (PN). Omega-6 reducing strategies may improve outcomes, including reduced PN associated liver disease, however evidence to support this recommendation is insufficient. The primary objective was to compare serum alkaline phosphatase (ALP), among patients provided with either soybean oil (Intralipid) or predominantly olive oil (Clinoleic) lipid emulsions. In this quasi-experimental study, we reviewed the medical records of surgical and medical adult patients who received lipid emulsions for at least seven consecutive days. Among the 206 patients (110-Intralipid, 96-Clinoleic) there was no significant difference in ALP and remaining liver function tests within 2 weeks of PN therapy initiation between groups, even after control for lipid doses. Macronutrient dosing was similar. Triglyceride level was higher by 0.7 mmol/L in the Clinoleic group; confidence interval 0.21 to 1.1; p = 0.004. The 30-day mortality, length of hospital stay, and proportion of patients admitted to intensive care were not significantly different. The Clinoleic group had a higher infection rate (36% vs. 22%, p = 0.031) and longer intensive care stays (p = 0.045). Well-designed randomized clinical trials comparing these lipid emulsions are necessary to confirm Intralipid superiority over Clinoleic in relation to infections and serum triglycerides.

Protein intakes are associated with reduced length of stay: a comparison between Enhanced Recovery After Surgery (ERAS) and conventional care after elective colorectal surgery.

Background: Protein can modulate the surgical stress response and postoperative catabolism. Enhanced Recovery After Surgery (ERAS) protocols are evidence-based care bundles that reduce morbidity.Objective: In this study, we compared protein adequacy as well as energy intakes, gut function, clinical outcomes, and how well nutritional variables predict length of hospital stay (LOS) in patients receiving ERAS protocols and conventional care.Design: We conducted a prospective cohort study in adult elective colorectal resection patients after conventional (n = 46) and ERAS (n = 69) care. Data collected included preoperative Malnutrition Screening Tool (MST) score, 3-d food records, postoperative nausea, LOS, and complications. Multivariable regression analysis assessed whether low protein intakes and the MST score were predictive of LOS.Results: Total protein intakes were significantly higher in the ERAS group due to the inclusion of oral nutrition supplements (conventional group: 0.33 g · kg-1 · d-1; ERAS group: 0.54 g · kg-1 · d-1; P < 0.02). This group difference in protein intake was maintained in a multivariable model that controlled for differences between baseline and surgical variables (P = 0.001). Oral food intake did not differ between the 2 groups. The ERAS group had shorter LOS (P = 0.049) and fewer total infectious complications (P = 0.01). Nausea was a predictor of protein intake. Nutrition variables were independent predictors of earlier discharge after potential confounders were controlled for. Each unit increase in preoperative MST score predicted longer LOSs of 2.5 d (95% CI: 1.5, 3.5 d; P < 0.001), and the consumption of ≥60% of protein requirements during the first 3 d of hospitalization was associated with a shorter LOS of 4.4 d (95% CI: -6.8, -2.0 d; P < 0.001).Conclusions: ERAS patients consumed more protein due to the inclusion of oral nutrition supplements. However, total protein intake remained inadequate to meet recommendations. Consumption of ≥60% protein needs after surgery and MST scores were independent predictors of LOS. This trial was registered at clinicaltrials.gov as NCT02940665.

Adequate Vitamin D Intake but Low Serum Levels in Pediatric Asthma Patients: A Pilot Study, Alberta Children's Hospital.

Background. We assessed vitamin D intakes and serum 25(OH) vitamin D levels in pediatric asthma patients on moderate-to-high dose inhaled steroids and compared them to published findings of healthy children in our city. Methods. Parents and/or patients were interviewed to estimate the children's vitamin D intakes from foods and supplements (using an adapted validated food frequency questionnaire) and asthma duration and management. Vitamin D status: serum 25-hyroxy vitamin D (25(OH)D) was obtained from the medical records. Results. Vitamin D intakes from food and supplements of the asthma patients (n = 20, 742 ± 185 IU/day) were significantly higher compared to healthy Canadian children (n = 1442, 229 ± 121 IU/day). Despite higher vitamin D intakes, the children had nonsignificantly lower serum 25(OH) vitamin D levels compared to the comparison group. Serum 25(OH)D levels increased by 3.6 nmol/L with each 100 IU of vitamin D intake (95% Confidence interval = 2.0-4.0, R2 = 0.931, and p = 0.001). Conclusion. Since adequate vitamin D status in asthma patients is necessary to support bone mineral accretion, it is important to achieve adequate vitamin D status by checking serum 25(OH)D status and supplement accordingly.

A systematic review and meta-analysis of the nutrient content of preterm and term breast milk.

BACKGROUND: Breast milk nutrient content varies with prematurity and postnatal age. Our aims were to conduct a meta-analysis of preterm and term breast milk nutrient content (energy, protein, lactose, oligosaccharides, fat, calcium, and phosphorus); and to assess the influence of gestational and postnatal age. Additionally we assessed for differences by laboratory methods for: energy (measured vs. calculated estimates) and protein (true protein measurement vs. the total nitrogen estimates). METHODS: Systematic review results were summarized graphically to illustrate the changes in composition over time for term and preterm milk. Since breast milk fat content varies within feeds and diurnally, to obtain accurate estimates we limited the meta-analyses for fat and energy to 24-hour breast milk collections. RESULTS: Forty-one studies met the inclusion criteria: 26 (843 mothers) preterm studies and 30 (2299 mothers) term studies of breast milk composition. Preterm milk was higher in true protein than term milk, with differences up to 35% (0.7 g/dL) in colostrum, however, after postnatal day 3, most of the differences in true protein between preterm and term milk were within 0.2 g/dL, and the week 10-12 estimates suggested that term milk may be the same as preterm milk by that age. Colostrum was higher than mature milk for protein, and lower than mature milk for energy, fat and lactose for both preterm and term milk. Breast milk composition was relatively stable between 2 and 12 weeks. With milk maturation, there was a narrowing of the protein variance. Energy estimates differed whether measured or calculated, from -9 to 13%; true protein measurement vs. the total nitrogen estimates differed by 1 to 37%. CONCLUSIONS: Although breast milk is highly variable between individuals, postnatal age and gestational stage (preterm versus term) were found to be important predictors of breast milk content. Energy content of breast milk calculated from the macronutrients provides poor estimates of measured energy, and protein estimated from the nitrogen over-estimates the protein milk content. When breast milk energy, macronutrient and mineral content cannot be directly measured the average values from these meta-analyses may provide useful estimates of mother's milk energy and nutrient content.

An exploratory study of sodium, potassium, and fluid nutrition status of tube-fed nonambulatory children with severe cerebral palsy.

Children with severe cerebral palsy (CP) often have lower mineral intakes than healthy children. It is unknown if their lower nutrient intakes are adequate to meet their needs. The objective of this study was to examine the sodium, potassium, phosphate, and fluid status of primarily tube-fed nonambulatory children with severe CP. The design consisted of a cross-sectional exploratory study and a clinical trial of sodium supplementation. Nutritional status was determined among primarily tube-fed children (aged 2 to 17 years) with CP based on blood and urine samples, anthropometry, and 3-day food records. Mineral and fluid status was evaluated by a nephrologist blind to nutrient intakes. Twenty children supplied food records, blood samples, and anthropometric measurements, and 16 supplied urine samples. Six (37.5%) of those who provided urine samples were considered possibly dehydrated, as urine osmolality was >600 mmol·kg(-1). Six (60%) of the 10 children with satisfactory fluid status (low urine osmolality) were considered to have a possible dietary sodium deficiency based on a very low urine sodium concentration (<20 mmol·L(-1)). Those considered to have a possible dietary sodium deficiency had a significantly lower sodium intake (48% ± 15% Adequate Intake (AI)) compared with those considered sodium sufficient (73% ± 20% AI) (p = 0.031). One child was considered possibly phosphorus deficient, but none was assessed as likely potassium deficient. The conclusion was that sodium deficiencies were likely prevalent among the children. The findings from this small observational study suggest that sodium intakes for tube-fed children with CP should be maintained near the AI for their age. Hydration status of children receiving hypercaloric formulas should be monitored.

Prevalence of vitamin D deficiency and response to oral vitamin D supplementation in patients receiving home parenteral nutrition.

UNLABELLED: The purpose of this study was to document vitamin D status in home parenteral nutrition (HPN) patients and determine if oral vitamin D supplementation has a substantial effect. METHODS: A retrospective chart review of eligible adults enrolled in the Southern Alberta Home Parenteral Nutrition program (n = 15) for a minimum of 6 months was conducted. Serum measurements of 25OHD were recorded and patients were categorized by vitamin D status as follows: sufficient; insufficient; deficient with respective levels of 25OHD ≥75 nmol/L, 27.5-75 nmol/L, and ≤27.5 nmol/L; and mixed. RESULTS: Five of 15 patients had insufficient vitamin D status throughout the study period; all had short bowel syndrome. Nine were in the mixed category; 1 was consistently sufficient, and no one was consistently deficient. Patient demographics were similar between the insufficient and mixed groups. There were no significant differences in health outcomes between the insufficient and mixed vitamin D status groups. The median (interquartile range) dose and duration of vitamin D3 supplementation for the insufficient group was 5000 IU/d (4,000-7,143) for 1,175 (1,145-1,578) total days compared to 3,000 IU/d (1,000-7,143) for 1,529 (111-1,980) days for the mixed group. CONCLUSIONS: Most patients receiving HPN had insufficient vitamin D status. When prescribed high doses of oral vitamin D, patients did not consistently achieve appropriate 25OHD levels. Alternate routes of vitamin D supplementation in patients receiving HPN should be considered. Large multicenter prospective studies are needed to best characterize the relationship between vitamin D dosing for HPN patients and vitamin D status.

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality.

BACKGROUND: Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. METHODS: Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. RESULTS: Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. CONCLUSIONS: A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.

Phosphate decreases urine calcium and increases calcium balance: a meta-analysis of the osteoporosis acid-ash diet hypothesis.

BACKGROUND: The acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a) to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b) level of calcium intake, c) the degree of protonation of the phosphate. METHODS: Literature was identified through computerized searches regarding phosphate with surrogate and/or direct markers of bone health, and was assessed for methodological quality. Multiple linear regression analyses, weighted for sample size, were used to combine the study results. Tests of interaction included stratification by calcium intake and degree of protonation of the phosphate supplement. RESULTS: Twelve studies including 30 intervention arms manipulated 269 subjects' phosphate intakes. Three studies reported net acid excretion. All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low, regardless of the degree of protonation of the phosphate supplement. None of the meta-analyses revealed lower calcium balance in response to increased phosphate intakes, whether the calcium intake was high or low, or the composition of the phosphate supplement. CONCLUSION: All of the findings from this meta-analysis were contrary to the acid ash hypothesis. Higher phosphate intakes were associated with decreased urine calcium and increased calcium retention. This meta-analysis did not find evidence that phosphate intake contributes to demineralization of bone or to bone calcium excretion in the urine. Dietary advice that dairy products, meats, and grains are detrimental to bone health due to "acidic" phosphate content needs reassessment. There is no evidence that higher phosphate intakes are detrimental to bone health.