Guidelines for parenteral nutrition in preterm infants: The American Society for Parenteral and Enteral Nutrition.

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.

Tolerability and safety of a semi-elemental enteral formula with partially hydrolyzed guar gum (PHGG) in tube-fed children aged 1-4 years: An open-label, single-arm study.

BACKGROUND AND AIMS: Partially hydrolyzed guar gum (PHGG) is a water-soluble fiber supporting digestive health with well-established safety and efficacy. This open-label, single-arm, multicenter trial aimed to assess the tolerability and safety of a semi-elemental enteral formula containing PHGG at 12 g/L in tube-fed young children. METHODS: Children aged 1-4 years with stable conditions requiring tube feeding to provide ≥80% of their nutritional needs received the study formula for seven days. Tolerability, safety, adequacy of energy/protein intake, and weight change were assessed. RESULTS: Of 24 children (mean age 33.5 months; 10 [41.7%] female), 23 (95.8%) commenced treatment and 18 (75%) completed the study. All children had underlying neuro-developmental disabilities, often in association with gastrointestinal comorbidities requiring treatment for constipation (70.8%) or gastroesophageal reflux (66.7%). The formula was well-tolerated by 19 (82.6%) subjects, while 4 (17.4%; 95% CI: 5%, 39%) subjects withdrew early from the study due to gastrointestinal intolerance. The mean (SD) percentage energy and protein intake across the 7-day period were 103.5% (24.7) and 139.5% [50], respectively. Weight remained stable over the 7-day period (p = 0.43). The study formula was associated with a shift towards softer and more frequent stools. Pre-existing constipation was generally well controlled, and 3/16 (18.7%) subjects ceased laxatives during the study. Adverse events were reported in 12 (52%) subjects and were deemed 'probably related' or 'related' to the formula in 3 (13%) subjects. Gastrointestinal adverse events appeared more common in fiber-naïve patients (p = 0.09). CONCLUSION: The present study indicates that the study formula was safe and generally well tolerated in young tube-fed children. GOV IDENTIFIER: NCT04516213.

Growth After Menarche in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Growth impairment in pediatric patients with pediatric onset inflammatory bowel disease (IBD) is multifactorial. Reports on the effect of age at menarche on adult stature in this population are limited. This study investigated the impact of age at menarche, disease-associated factors, and mid-parental height on growth from menarche to final height (FHt) in pediatric patients with Crohn disease (CD) and ulcerative colitis (UC) and IBD unclassified (IBD-U). METHODS: Subjects were enrolled from a prospectively maintained pediatric IBD database when IBD preceded menarche and dates of menarche and FHt measurements were recorded. RESULTS: One hundred forty-six patients: CD 112 and UC 30/IBD-U 4. Mean age (years) at diagnosis (10.9 vs 10.1), menarche (14.4 vs 14.0), and FHt (19.6 vs 19.7). CD and UC/IBD-U patients showed significant association between Chronological age (CA) at menarche and FHt (cm, P < 0.001) but not FHt z score (FHt-Z) < -1.0 (P = 0.42). FHt-Z < -2.0 occurred in only 5 patients. Growth impairment (FHt-Z < -1.0) was associated with surgery before menarche (P = 0.03), jejunal disease (P = 0.003), low mid-parental height z score (MPH-Z) (P < 0.001), hospitalization for CD (P = 0.03) but not UC, recurrent corticosteroid, or anti-tumor necrosis factor alpha (anti-TNFα) therapy. CONCLUSIONS: Early age of menarche was associated with greater potential for linear growth to FHt but not FHt-Z (P < 0.05). Surgery before menarche, jejunal disease, hospitalization for CD, low MPH, and weight z score were associated with FHt-Z < -1.0.

Factors Affecting Selenium Status in Infants on Parenteral Nutrition Therapy.

INTRODUCTION: Selenium is an essential micronutrient that must be supplemented in infants and young children on exclusive parenteral nutrition (PN). We examined selenium status and clinical factors associated with a deficiency in infants on PN. METHODS: This was a retrospective cohort study of pediatric patients receiving PN with routine monitoring of selenium status. Deficiency was diagnosed using age-based norms of plasma selenium status. Associations between selenium deficiency and the following clinical factors were examined: birthweight status: extremely low birthweight (ELBW) versus very low birthweight (VLBW) versus low birthweight (LBW) versus normal birthweight (NBW), serum albumin status, presence of cholestasis, and co-administration of enteral feeds. RESULTS: A total of 42 infants were included with gestational age [median (interquartile range)] 28 weeks (25,34). The prevalence of selenium deficiency was 80% and the prevalence of albumin deficiency was 87.5%. The odds of selenium deficiency were higher in ELBW infants (odds ratio = 17.84, 95% confidence interval [4.04-78.72], P < 0.001) and VLBW infants (odds ratio = 16.26, 95% confidence interval [1.96-135.04], P < 0.001) compared to NBW infants. The odds of selenium deficiency were 5-fold higher in patients with low serum albumin (odds ratio = 5.33, 95% confidence interval [1.39-20.42], P = 0.015). There were no associations seen between selenium status and presence of cholestasis or co-administration of enteral feeds. CONCLUSION: In this cohort of infants on PN therapy, the main clinical factors associated with selenium deficiency were presence of hypoalbuminemia and history of ELBW or VLBW. These findings support dual measurement of serum albumin and serum selenium to improve interpretation of selenium status.

NASPGHAN Nutrition University (N2U): A Survey of its Efficacy as Continuing Nutrition Education for North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) developed NASPGHAN Nutrition University (N2U) in 2012 to improve nutrition education for pediatric gastroenterology providers. A total of 543 providers (physicians, registered dietitians, and advanced practice nurses) have applied to N2U and 285 have attended this 2-day course. We used survey methodology to compare attendees to applicants who did not attend. Course attendees reported more confidence than nonattendees in the nutritional management of patients with short bowel syndrome, feeding disorders, and gastrointestinal allergies, even though they were seen at similar frequency in both groups. Eighty-eight percent of attendees disseminated the information they learned at N2U through venues such as grand rounds or guideline/policy development. These results demonstrate the benefit of N2U in enhancing nutrition education for pediatric gastroenterology practitioners.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper: Plant-based Milks.

Parents and caretakers are increasingly feeding infants and young children plant-based "milk" (PBM) alternatives to cow milk (CM). The US Food and Drug Administration currently defines "milk" and related milk products by the product source and the inherent nutrients provided by bovine milk. Substitution of a milk that does not provide a similar nutritional profile to CM can be deleterious to a child's nutritional status, growth, and development. Milk's contribution to the protein intake of young children is especially important. For almond or rice milk, an 8 oz serving provides only about 2% or 8%, respectively, of the protein equivalent found in a serving of CM. Adverse effects from the misuse of certain plant-based beverages have been well-documented and include failure to gain weight, decreased stature, kwashiorkor, electrolyte disorders, kidney stones, and severe nutrient deficiencies including iron deficiency anemia, rickets, and scurvy. Such adverse nutritional outcomes are largely preventable. It is the position of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Nutrition Committee, on behalf of the society, that only appropriate commercial infant formulas be used as alternatives to human milk in the first year of life. In young children beyond the first year of life requiring a dairy-free diet, commercial formula may be a preferable alternative to cow's milk, when such formula constitutes a substantial source of otherwise absent or reduced nutrients (eg, protein, calcium, vitamin D) in the child's restricted diet. Consumer education is required to clarify that PBMs do not represent an equivalent source of such nutrients. In this position paper, we provide specific recommendations for clinical care, labelling, and needed research relative to PBMs.

A New Approach to Comprehensive Growth and Nutrition Assessment in Children.

A new approach to comprehensive growth and nutrition assessment of infants, children, and adolescents that is etiology based and relatively simple to implement is now available. It encompasses five domains: anthropometry (growth measurements), assessment of change in growth (growth dynamism), duration of the growth abnormalities, etiology of the nutritional imbalance, and impact of the nutritional state on functional outcomes. Its increased use will help to standardize the screening, diagnosis, and documentation of malnutrition in both ambulatory and hospitalized patients. [Pediatr Ann. 2019;48(11):e425-e433.].

The ABCs of Nutrient Deficiencies and Toxicities.

Vitamins and minerals are part of a well-balanced diet. They are essential for normal growth and development, which is especially crucial for the pediatric population. Vitamins are divided based on their solubility into fat-soluble vitamins, which include vitamins A, D, E, and K and water-soluble vitamins, which include the B vitamins and vitamin C. Minerals include calcium, magnesium, and phosphorus. Trace minerals are micronutrients and include copper, zinc, selenium, chromium and manganese. The pediatrician is often the first health care provider to interface with patients, allowing them to pick up on nutritional derangements. This article reviews the basic sources, absorption, metabolism as well as the signs and symptoms that arise in deficient and toxic states of fat-soluble vitamins, water-soluble vitamins, minerals, and trace elements. [Pediatr Ann. 2019;48(11):e434-e440.].

Pancreatic Malnutrition in Children.

Exocrine pancreatic insufficiency in children can lead to lifelong complications related to malnutrition and poor growth. The clinical presentation can be subtle in the early stages of insufficiency as the large functional capacity of the pancreas is gradually lost. The pediatrician plays a crucial role in the early identification of these children to ensure a timely referral so that a diagnosis can be made and therapy initiated. Early nutritional therapy allows for prevention and correction of deficiencies, which leads to improved outcomes and survival. When insufficiency is suspected, the workup should start with an indirect test of exocrine pancreatic function, such as fecal elastase, to establish the diagnosis. Once a diagnosis is established, further testing to delineate the etiology should be pursued, with cystic fibrosis being high on the differential list and assessed for with a sweat test. Assessment of anthropometry at every visit is key, as is monitoring of laboratory parameters and physical examination findings that are suggestive of malabsorption and malnutrition. The mainstay of management is administration of exogenous pancreatic enzymes to facilitate digestion and absorption. [Pediatr Ann. 2019;48(11):e441-e447.].

Refeeding Syndrome.

Refeeding syndrome describes the metabolic disturbances and clinical sequelae that occur in response to nutritional rehabilitation of patients who are moderate to severely malnourished. When risk factors are not identified and nutrition therapy is not managed appropriately, devastating consequences such as electrolyte depletion and imbalances, fluid overload, arrhythmia, seizure, encephalopathy, and death may occur. As this entity is often unrecognized, especially in pediatrics, becoming familiar with the pathophysiology, clinical manifestations, and management strategies will help clinicians caring for children avoid unnecessary morbidity and mortality. [Pediatr Ann. 2019;48(11):e448-e454.].

Hypophosphatemia in a Malnourished Child: When Renal Fanconi Syndrome Does Not Stand for Refeeding Syndrome.

Refeeding syndrome is diagnosed based on the onset of multiple laboratory abnormalities (most commonly hypophosphatemia) and clinical signs in the setting of nutrition rehabilitation of malnourished patients. Because definitions are not uniform, a broad differential diagnosis should always include renal tubular dysfunction. Our report details a 3 year-old child with undiagnosed renal tubular dysfunction who presented with the clinical picture of refeeding syndrome with refractory electrolyte abnormalities. A diagnosis of renal Fanconi syndrome was made after urinalysis that revealed glucosuria and urine electrolyte losses. Thus, urinalysis can aid in making a positive diagnosis of refeeding syndrome.

Effects of Chromium on Glucose Tolerance in Infants Receiving Parenteral Nutrition Therapy.

OBJECTIVES: Early hyperglycemia is prevalent in preterm infants receiving parenteral nutrition (PN) therapy. Chromium improves glucose tolerance by potentiating the action of insulin. Therefore, we hypothesized that supplementing PN with chromium would improve glucose tolerance and PN calorie delivery in infants during the first week of life. METHODS: We collected data on neonates receiving PN initiated at birth with chromium (0.2 mcg/kg/d) started either on days 5-7 (group A) vs day 1 (group B) on PN and compared glucose tolerance and PN calorie administration over the first week of life. RESULTS: For similar mean serum glucose concentrations between group A (n = 348) and B (n = 358) (107 ± 48 vs 111 ± 52 mg/dL, P = .3), infants in group B tolerated higher glucose infusion rates and received more PN calories during the first week of life: 8.4 ± 2 vs 8 ± 2 mg/kg/min (P < .001) and 74.8 ± 23 vs 71.5 ± 12 kcal/kg/d (P = .017), respectively. The difference in calories delivered was more pronounced among very low birth weight (VLBW) infants compared with infants >1500 g: 76.5 ± 14 vs 72.4 ± 11 kcal/kg/d (P = .009) and 73.8 ± 27 vs 70.3 ± 12 kcal/kg/d (P = .079), respectively. CONCLUSIONS: PN chromium supplementation resulted in better glucose tolerance and calorie delivery during the first week of life, especially in VLBW infants. This supports chromium's essential role in enhancing glucose tolerance during PN therapy in VLBW infants at risk for early hyperglycemia.

Safety and Pharmacokinetic Study of Fidaxomicin in Children With Clostridium difficile-Associated Diarrhea: A Phase 2a Multicenter Clinical Trial.

BACKGROUND: Fidaxomicin is an approved therapy for Clostridium difficile-associated diarrhea (CDAD) in adults. The safety of fidaxomicin in children has not been reported. METHODS: In this study (ClinicalTrials.gov identifier NCT01591863), pediatric patients with CDAD received twice-daily oral fidaxomicin at a dose of 16 mg/kg per day (up to 200 mg) for 10 days in an open-label study. Plasma and fecal samples were collected for pharmacokinetic assessments. The primary outcome measure was safety, which was assessed by adverse-event (AE), laboratory, and physical examination/vital-sign monitoring. Efficacy was determined through early and sustained clinical response rates (clinical response without recurrence of CDAD). RESULTS: The study enrolled 40 patients (11 months to 17 years of age), many with underlying comorbidity, including neoplasm (23.7%), gastrointestinal disorder (78.9%), and history of CDAD (60.5%). Plasma fidaxomicin and OP-1118 (the major fidaxomicin metabolite) 3- to 5-hour postdose concentrations were 0.6 to 87.4 and 2.4 to 882.0 ng/mL, respectively, and no age-related trends were seen. Fecal fidaxomicin concentrations within 24 hours of the last dose averaged 3228 µg/g, and higher concentrations and greater variability in the youngest age group were found. AEs were reported in 73.7% of the patients; most of them were mild (44.7%) to moderate (21.1%) and were considered treatment-related in 15.8% of the patients. Overall, the early clinical response rate was 92.1%. The rate of sustained clinical response (clinical response without recurrence through 28 days after treatment) was 65.8% overall. CONCLUSIONS: Fidaxomicin was well tolerated in children with CDAD and has a pharmacokinetic profile in children similar to that in adults. The clinical response rate was high.

Intestinal Rehabilitation Programs in the Management of Pediatric Intestinal Failure and Short Bowel Syndrome.

Intestinal failure is a rare, debilitating condition that presents both acute and chronic medical management challenges. The condition is incompatible with life in the absence of the safe application of specialized and individualized medical therapy that includes surgery, medical equipment, nutritional products, and standard nursing care. Intestinal rehabilitation programs are best suited to provide such complex care with the goal of achieving enteral autonomy and oral feeding with or without intestinal transplantation. These programs almost all include pediatric surgeons, pediatric gastroenterologists, specialized nurses, and dietitians; many also include a variety of other medical and allied medical specialists. Intestinal rehabilitation programs provide integrated interdisciplinary care, more discussion of patient management by involved specialists, continuity of care through various treatment interventions, close follow-up of outpatients, improved patient and family education, earlier treatment of complications, and learning from the accumulated patient databases. Quality assurance and research collaboration among centers are also goals of many of these programs. The combined and coordinated talents and skills of multiple types of health care practitioners have the potential to ameliorate the impact of intestinal failure and improve health outcomes and quality of life.

Colonic Necrosis in a 4-Year-Old with Hyperlipidemic Acute Pancreatitis.

Here we report the case of a 4-year-old male with severe acute pancreatitis due to hyperlipidemia, who presented with abdominal pain, metabolic abnormalities, and colonic necrosis. This colonic complication was secondary to the extension of a large peripancreatic fluid collection causing direct serosal autodigestion by pancreatic enzymes. Two weeks following the initial presentation, the peripancreatic fluid collection developed into a mature pancreatic pseudocyst, which was percutaneously drained. To our knowledge, this is the youngest documented pediatric case of colonic necrosis due to severe pancreatitis and the first descriptive pediatric case of a colonic complication due to hyperlipidemia-induced acute pancreatitis.