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.

Variability of resting energy expenditure in infants and young children with intestinal failure-associated liver disease.

OBJECTIVE: The aim of the study was to determine, in a cohort of young children with intestinal failure (IF), whether the estimates of basal metabolic rate (BMR) by standard equations can approximate measured resting energy expenditure (REE) by indirect calorimetry (IC). METHODS: IC was performed using the dilutional canopy technique. REE measurements were compared with standard, age-based estimation equations (World Health Organization) for BMR. Subjects were classified as hypermetabolic (REE > 110% BMR), hypometabolic (REE < 90% BMR), or normal (REE = 90%-110% BMR). RESULTS: Twenty-eight IF patients (11 girls, 17 boys) had an underlying diagnosis of necrotizing enterocolitis (n = 10) or a congenital gastrointestinal defect (n = 18). Median age was 5.3 months. Median interquartile range (IQR) REE was 46 (42-58) kcal · kg · day. Median (IQR) total energy intake provided 209% (172%-257%) of REE, with parenteral nutrition providing 76% (23%) of total energy intake. REE was variable, with 39% (n = 11) of measurements hypermetabolic, 39% (n = 11) hypometabolic, and the remaining 21% (n = 6) normal. Although REE was well correlated with estimated BMR (r = 0.82, P < 0.0001), estimated BMR was not consistently an adequate predictor of REE. BMR over- or underestimated REE by >10 kcal · kg · day in 15 of 28 (54%) patients. REE was not significantly correlated with severity of liver disease, nutritional status, total energy intake, or gestational age. CONCLUSIONS: Energy expenditure is variable among children with IF and IF-associated liver disease, with approximately 80% of our cohort exhibiting either hypo- or hypermetabolism. Standard estimation equations frequently do not correctly predict individual REE. Longitudinal studies of energy expenditure and body composition may be needed to guide provision of nutrition regimens.

A retrospective review of the 5-year nutritional and clinical outcomes in pediatric patients undergoing intestinal rehabilitation.

BACKGROUND: The mainstay of modern medical therapy for intestinal failure (IF) is parenteral nutrition (PN). The Intestinal Rehabilitation Program (IRP) goal is enhancing nutritional outcomes for patients receiving total parenteral nutrition (TPN), optimizing/transitioning patients from TPN to enteral nutrition (EN), achieving enteral autonomy, monitoring growth and development. The objective of this study is to describe nutritional and clinical outcomes for children undergoing intestinal rehabilitation during 5 years of the program. METHODS: Retrospective chart review for children from birth to <18 years old with IF who were on TPN from July 2015 to Dec 2020 or to the endpoint of the study when they either weaned from TPN during the 5 year period or continued TPN by Dec 2020 and participated at our IRP. RESULTS: The mean age of the cohort was 2.4 years (±4.22), 53% male. The 3 most common diagnosis were necrotizing enterocolitis (28%), gastroschisis (14%) and intestinal atresia (14%). Nutritional data including days/hours per week on TPN, glucose infusion rate, amino acids, total EN calories, % of total nutrition received from TPN and EN per day all showed statistically significant differences. Our program showed 0% intestinal failure associated liver disease (IFALD), 0% mortality, 100% survival, 41% patients were weaned from TPN (13/32) with mean of 39 months (±32). CONCLUSION: Early referral to a center that can offer IRP, such as ours can lead to tremendous positive clinical outcomes and help patients with intestinal failure avoid transplant as shown in our study.

Comparison of Home-Blenderized Formula and Commercial Enteral Formulas for Gastrostomy Tube-Fed Children: A Retrospective, Prospective Cohort Study.

Background Blenderized gastrostomy tube feedings (BGTFs) consist of pureed table foods and liquids that are administered as enteral tube feedings. Compared to commercial enteral formulas (CEFs), BGTF has been shown to have fewer side effects. Despite these results, apprehensions have been raised about microbial contamination, nutritional deficiencies or surplus, risk of gastrostomy tube (GT) blockages, and lack of consistency in clinical outcomes. The goal of this retrospective, prospective, 18-month-long study is to report the clinical and nutritional outcomes of GT-dependent pediatric patients who attended a multidisciplinary feeding clinic. Methodology After Institutional Review Board (IRB) approval and consent were obtained, 25 children who were receiving tube feeding via G were enrolled in a retrospective, prospective, observational, cohort study from August 2019 to February 2021. A multidisciplinary team was formed, and multivariate logistic regression was performed comparing subjects on BGTF versus CEF, per os diet versus nil per os, CEF versus homemade blenderized tube feeding (HBTF) versus blenderized tube feeding (BTF), and how they compared at the beginning and end of the study. Results The mean age of the patients was 4.4 years (SD ±2.2). Gastroesophageal reflux disease (GERD) and short bowel syndrome (SBS) were the most common comorbid gastrointestinal (GI) conditions. Of the 25 patients enrolled in the study, seven were initially on BGTF, while 14 ended the study on BGTF. There were no statistically significant differences in malnutrition status, feeding intolerance, emergency room visits, hospitalizations, and GT blockages between all different comparison groups when comparing between the CEF versus HBTF versus commercial blenderized tube feeding (CBTF) groups. Of the patients who were in the BGTF group, there was a resolution of vitamin A deficiency, vitamin D deficiency, and anemia (n = 1). In total, two patients had resolved vitamin deficiencies, namely, vitamins A and D. Conclusions When comparing BGTF and CEF, there was no statistically significant difference in outcomes. This study suggests that BGTF is at least equivalent to CEF in clinical outcomes, meaning BGTF should be considered standard nutrition for GT-dependent patients.

Trends in liver profile and nutrition outcomes in children undergoing intestinal rehabilitation using a mixed lipid injectable emulsion.

BACKGROUND: Pediatric patients undergoing intestinal rehabilitation (IR) using parenteral nutrition (PN) are at higher risk for intestinal failure-associated liver disease (IFALD). Nutrition support, growth, and liver enzymes must be closely monitored while incorporating hepatoprotective lipid injectable emulsions for optimal patient outcomes. OBJECTIVE: Describe trends of liver profile and nutrition outcomes for pediatric patients undergoing IR using SMOFlipid[SO,MCT,OO,FO-ILE]). METHODS: After IRB approval, patients undergoing IR using SO,MCT,OO,FO-ILE were observed prospectively from January 1, 2017, through December 1, 2019. The following values were documented monthly: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), triene/tetraene ratio (TTR), micronutrient and trace element levels, z-scores for growth, and nutrition support regimen. Values were compared. RESULTS: The group involved 16 pediatric patients for an average of 16.4 months on SO,MCT,OO,FO-ILE. By the end of the study, mean PN hours per day decreased by 34.7%, P < 0.0001. Mean PN calories per kilogram decreased from 60.4 to 48.3, P = 0.004. SO,MCT,OO,FO-ILE calories met the recommended dietary intake goal of 30% at the average 1.6 g/kg. Growth z-scores increased in those <2 YOA , although the body mass index decreased in our >2 YOA cohort. Total nutrition received from PN decreased to 62%: a 32% change, P = 0.001. There were no statistically significant changes in AST or ALT. TB decreased by 67.08%, P <0.05. No essential fatty acid deficiency was reported (TTR < 0.02). There were no changes in micronutrient and trace element deficiencies. There was zero new incidences of IFALD. CONCLUSIONS: SO,MCT,OO,FO-ILE may be used long term in pediatric patients while promoting growth and development.

A Multidisciplinary Approach and Development of an Algorithm for Timely Repair of Central Venous Access in Pediatric Patients.

BACKGROUND: Central venous catheters (CVCs) carry a risk for many complications. This can lead to numerous and prolonged hospitalizations for patients undergoing intravenous nutrition. The aim was to create a standardized protocol for the medical facility to expedite the repair process as well as implement a broadened educational effort for the care of CVCs. METHOD: A retrospective chart review was completed for 365 catheter days before implementation. Two protocols were then created in collaboration with the multidisciplinary team. Prospective chart data were subsequently collected 365 catheter days post-implementation. RESULT: Pre-implementation (32 encounters), 100% of compromised CVCs required admission. Post-implementation (21 encounters), only 48% of compromised CVCs required admission accompanied by an overall reduction in the number of compromised catheters that presented to the hospital. The average hospital length of stay pre-protocol initiation decreased from 7.2 to 1.8 days post-protocol initiation. The implementation of our algorithm also lead to a decrease in the average cost of compromised CVC repair inpatient ($2741) vs repair in the emergency department ($34,436). CONCLUSION: This study demonstrates that working with a multidisciplinary team utilizing a standardized protocol improved the quality of patient care by decreasing hospital admissions for compromised CVCs. The authors also conclude that the expedited repair of CVCs can help alleviate health care costs for both families and the hospital system.

High prevalence of multiple micronutrient deficiencies in children with intestinal failure: a longitudinal study.

OBJECTIVE: To determine the prevalence of micronutrient deficiencies in children with intestinal failure as they transitioned from parenteral nutrition (PN) to enteral nutrition (EN). STUDY DESIGN: We reviewed medical records of all patients with severe intestinal failure treated from 1999 to 2008 at a multidisciplinary intestinal rehabilitation program who had undergone micronutrient biochemical monitoring. RESULTS: The cohort of 30 children (mean age, 5 years; range, 2 to 9 years; 18 boys) had median PN duration of 23 weeks (IQR, 13 to 34 weeks). Median transition from PN to full EN lasted 12 weeks (IQR, 8 to 20 weeks); during this transition, 33% of patients had at least one vitamin deficiency and 77% at least one mineral deficiency. After transition to 100% EN, 70% had at least one vitamin deficiency and 77% had at least one mineral deficiency, with the most common deficiencies being vitamin D (68%), zinc (67%), and iron deficiency (37%). After transition to 100% EN, multivariate analysis identified regular use of a multivitamin supplement (P=.004) and intact ileocecal valve (P=.02) as protective against the development of vitamin deficiencies, independent of bowel length, gestational age, and days on PN. CONCLUSIONS: Children with intestinal failure exhibit a high prevalence of micronutrient deficiencies during intestinal rehabilitation. Regular monitoring and aggressive supplementation in children with intestinal failure is warranted.

Risk factors for parenteral nutrition­associated liver disease following surgical therapy for necrotizing enterocolitis: A Glaser Pediatric Research Network Study [corrected].

OBJECTIVE: The aim of the study was to prospectively determine risk factors for the development of parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC), the most common cause of intestinal failure in children. PATIENTS AND METHODS: : From February 2004 to February 2007, we diagnosed 464 infants with NEC, of whom 180 had surgery. One hundred twenty-seven patients were available for full analysis. PNALD was defined as serum direct bilirubin ≥ 2 mg/dL or ALT ≥ 2 × the upper limit of normal in the absence of sepsis after ≥ 14 days of exposure to PN. RESULTS: Median gestational age was 26 weeks and 68% were boys. Seventy percent of the cohort developed PNALD and the incidence of PNALD varied significantly across the 6 study sites, ranging from 56% to 85% (P = 0.05). Multivariable logistic regression analysis identified small-bowel resection or creation of jejunostomy (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.97-12.51, P = 0.0007) and duration of PN in weeks (OR 2.37, 95% CI 1.56-3.60, P < 0.0001) as independent risk factors for PNALD. Preoperative exposure to PN was also associated with the development of PNALD; the risk of PNALD was 2.6 (95% CI 1.5-4.7; P = 0.001) times greater in patients with ≥ 4 weeks of preoperative PN compared with those with less preoperative PN use. Breast milk feedings, episodes of infection, and gestational age were not related to the development of PNALD. CONCLUSIONS: The incidence of PNALD is high in infants with NEC undergoing surgical treatment. Risk factors for PNALD are related to signs of NEC severity, including the need for small-bowel resection or proximal jejunostomy, as well as longer exposure to PN. Identification of these and other risk factors can help in the design of clinical trials for the prevention and treatment of PNALD and for clinical assessment of patients with NEC and prolonged PN dependence.

Thirty percent ethanol locks ineffective in preventing central line-associated bloodstream infection in pediatric intestinal rehabilitation patients.

BACKGROUND: Intestinal failure patients dependent on parental nutrition are reliant on central venous catheters and are at increased risk for central line-associated bloodstream infection (CLABSI). Seventy percent ethanol has been widely used for prophylaxis; however, it is known to have multiple adverse effects. This study demonstrates the implementation of a 30% ethanol lock protocol for CLABSI prevention in a community-based hospital intestinal rehabilitation program. METHODS: This case series reports rates of CLABSI, compromised central venous catheter, and analysis of community bacterial pathogens. RESULTS: A 42.1% increase in CLABSI and a 125% increase in compromised central venous catheters were noted after initiation of the 30% ethanol lock protocol. CONCLUSION: It can be concluded that for the pediatric intestinal rehabilitation patient, 30% ethanol did not provide adequate CLABSI prophylaxis. This study indicates the need for larger sample sizes or the use of other concentrations of ethanol locks ranging between 30% and 70%.

Reversal of Intestinal Failure-Associated Liver Disease in an Infant Treated With Mixed Lipid Emulsion and Multidisciplinary Intestinal Rehabilitation Program.

Intestinal failure-associated liver disease (IFALD) can lead to increased morbidity and mortality in patients with intestinal failure (IF). We report the case of a premature infant born at 25 weeks' gestation at a neighboring facility that developed surgical necrotizing enterocolitis and secondary IF with 6 cm of small bowel remaining measured from the ligament of treitz with jejunocolonic anastomosis. The patient's course was complicated by IFALD and transferred to our intestinal rehabilitation program at 3 months of age. He was treated with SMOF lipid in reduced lipid dosages to prevent and treat IFALD, including cycling of parenteral nutrition, monitoring of the glucose infusion rate, and adjusting the micronutrient, trace elements, and aggressive enteral feeding. Omegaven had not yet been approved during the time of this case presentation. During the course of his treatment, he experienced normalization of his liver profile tests and progressed toward enteral autonomy.

Risk factors for intestinal failure in infants with necrotizing enterocolitis: a Glaser Pediatric Research Network study.

OBJECTIVE: To determine risk factors for intestinal failure (IF) in infants undergoing surgery for necrotizing enterocolitis (NEC). STUDY DESIGN: Infants were enrolled in a multicenter prospective cohort study. IF was defined as the requirement for parenteral nutrition for >or= 90 days. Logistic regression was used to identify predictors of IF. RESULTS: Among 473 patients enrolled, 129 had surgery and had adequate follow-up data, and of these patients, 54 (42%) developed IF. Of the 265 patients who did not require surgery, 6 (2%) developed IF (OR 31.1, 95% CI, 12.9 - 75.1, P < .001). Multivariate analysis identified the following risk factors for IF: use of parenteral antibiotics on the day of NEC diagnosis (OR = 16.61, P = .022); birth weight < 750 grams, (OR = 9.09, P < .001); requirement for mechanical ventilation on the day of NEC diagnosis (OR = 6.16, P = .009); exposure to enteral feeding before NEC diagnosis (OR=4.05, P = .048); and percentage of small bowel resected (OR = 1.85 per 10 percentage point greater resection, P = .031). CONCLUSION: The incidence of IF among infants undergoing surgical treatment for NEC is high. Variables characteristic of severe NEC (low birth weight, antibiotic use, ventilator use, and greater extent of bowel resection) were associated with the development of IF.

[13C]Methionine breath test to assess intestinal failure-associated liver disease.

Oxidation of L[1-C]methionine ([C]-Met) in liver mitochondria can be quantified by measuring exhaled CO2. We hypothesized that CO2 recovery after i.v. administered [C]-Met would provide a noninvasive measure of liver function in pediatric intestinal failure-associated liver disease (IFALD). After Institutional Review Board (IRB) approval, 27 patients underwent L[1-C]-Met breath tests ([C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for CO2 enrichment using isotope ratio mass spectrometry. Pediatric end-stage liver disease (PELD) scores were recorded, and total carbon dioxide (CO2) production was measured by indirect calorimetry. Twenty-seven patients (median age = 5.3 mo) underwent a total of 34 [C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The [C]-MBT differentiated patients with and without cirrhosis (medians 210 and 350, respectively, p = 0.04). Serial [C]-MBTs in five patients reflected changing PELD scores. i.v. administering the stable isotope [C]-Met with serial breath sampling provides a useful, safe, and potentially clinically relevant evaluation of hepatic function in pediatric IFALD. The [C]-MBT may also help quantify progression or improvement of IFALD.

Overview of pediatric short bowel syndrome.

Short bowel syndrome (SBS) is a malabsorptive state occuring as a result of surgical resection or congenital disease of a significant portion of the small intestine . The amount of resection or remaining bowel generally dictates the degree of malabsorption and consequentely the need for specialized enteral nutrition or parenteral nutrition (PN). Intestinal failure in the context of SBS is defined as a dependence on PN to maintain minimal energy and fluid requirement for growth in children. Common causes of SBS in infants and children include necrotizing enterocolitis, midgut volvulus, intestinal atresia, and gastroschisis. Early identification of patients at risk for long-term PN dependency is the first step toward avoiding severe complications. Close monitoring of nutritional status, steady and early introduction of enteral nutrition, and aggressive prevention, diagnosis, and treatment of infections such as central venous catheter sepsis and bacterial overgrowth can significantly improve the prognosis. Intestinal transplantation is an emerging treatment that may be considered when intestinal failure is irreversible and children are experiencing serious complications related to TPN administration.

Weekly measurements accurately represent trends in resting energy expenditure in children undergoing hematopoietic stem cell transplantation.

BACKGROUND: Resting energy expenditure (REE) measurements are optimal for accurate assessment of energy requirements and precise provision of parenteral nutrients. We previously observed significant reduction in REE during a 4-week period in children undergoing hematopoietic stem cell transplantation (HSCT). The goal of this study was to determine if weekly REE measurements could accurately represent changes in REE in the peritransplant period compared with a more frequent standard of daily measurements. METHODS: Data are presented from a previously described cohort of 37 children undergoing HSCT. We performed weekly indirect calorimetry on 25 patients; of those 25, we performed daily measurements on a convenience sample of 5 children. The time course of REE was analyzed in each sample by repeated measures regression. RESULTS: The REE trend of the 20 weekly participants was similar to that of the 5 daily participants, reaching about 80% of predicted REE at 4 weeks posttransplant, with an average decline of 3.4% per week during 4 weeks. CONCLUSION: The results suggest that weekly REE measurements accurately characterize REE changes 4 weeks after HSCT compared with daily measurements. Characterization of these trends using weekly measurements may help guide clinical and nutrition care of these patients.

CNS or classic drugs for the treatment of pain in functional dyspepsia? A systematic review and meta-analysis of the literature.

BACKGROUND: Recent evidence has suggested that pain in functional dyspepsia (FD) is associated with nervous system dysfunction; indicating that therapies aimed at nervous system modulation might be associated with pain relief in FD. OBJECTIVE: To conduct a systematic review and meta-analysis to quantify the efficacy of drugs targeting the central nervous system (antidepressants and antianxiety agents - referred as "CNS drugs") and drugs targeting gastric modulation (antisecretory and prokinetic - referred as "classic drugs") for the treatment of pain in FD and, in an exploratory way, compare these 2 modalities of treatment. METHODS: MEDLINE and reference lists were examined for relevant articles. We included prospective studies that evaluated the effects of either CNS drugs or classic drugs (subdivided in prokinetic and antisecretory drugs) on the symptoms of FD. RESULTS: Seven studies for CNS drugs and 11 studies for gastric drugs met our inclusion criteria. The analyses of these drugs showed that the 2 groups of drugs are associated with a significant reduction in dyspeptic symptoms. The pooled effect size (standardized mean difference between pre-treatment versus post-treatment means) from the random effects model was 1.25 (95% C.I., 0.83, 1.67) for CNS; 1.63 (95% C.I., 1.28, 1.97) for prokinetic, and 0.93 (95% C.I., 0.57, 1.29) for antisecretory drugs. The exploratory comparison between classes of drugs revealed no significant difference in dyspeptic symptoms reduction between CNS and prokinetic drugs; however CNS drugs were associated with a larger reduction in symptoms as compared with antisecretory drugs. CONCLUSIONS: The results show that both CNS and classic drugs are associated with a significant pain reduction in functional dyspepsia.

Carbohydrate malabsorption may increase daily energy requirements in infants.

OBJECTIVE: Carbohydrate malabsorption in infants has been found to increase nutrient losses. However, the effect of this alteration on daily metabolic rate is unknown. We assessed daily metabolic rates in infants with asymptomatic carbohydrate malabsorption (ACM) after a single fruit juice load. METHODS: Sixteen healthy infants with ACM (63.3 +/- 5.6 cm, 7.5 +/- 1.0 kg, 5.6 +/- 0.8 mo, peak breath hydrogen [BH2] = 39.1 +/- 22.4 ppm) and 16 without ACM (64.3 +/- 3.9 cm, 7.8 +/- 1.0 kg, 5.0 +/- 0.8 mo, BH2 = 9.4 +/- 4.7 ppm), after a single fruit juice load, had 24-h energy expenditure (24-h EE; kcal x kg(-1) x d(-1)), resting (RMR; kcal x kg(-1) x d(-1)) and sleeping (SMR; kcal x kg(-1) x d(-1)) metabolic rates extrapolated from 3.5-h assessments in the Enhanced Metabolic Testing Activity Chamber. Furthermore, RMR was calculated with the World Health Organization (WHO), Schofield weight-based and weight- and height-based equations. Carbohydrate absorption was determined by BH2. Differences (P < 0.05) were determined by t test. RESULTS: All infants with ACM had greater (P < 0.05) extrapolated 24-h EE (91.2 +/- 24.8 versus 78.0 +/- 6.8) and RMR (71.8 +/- 15.2 versus 59.5 +/- 5.9). This represented an increase of 15-18.5%, respectively, in energy expenditures. Carbohydrate malabsorption was a significant determinant of EE, RMR, and SMR. However, the WHO (53.8 +/- 1.0 versus 54.1 +/- 0.9) and both Schofield equations (54.7 +/- 0.9 versus 54.9 +/- 1.0 and 50.6 +/- 7.5 versus 47.3 +/- 6.7) failed to detect any differences in RMR. There was a 20 percentile reduction in growth performance in infants with carbohydrate malabsorption. CONCLUSIONS: Infants with ACM following fruit juice ingestion may have increased daily energy expenditure leading to increased metabolic requirements.