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.

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.

Manifestations of Cow's-Milk Protein Intolerance in Preterm Infants.

OBJECTIVES: Cow's-milk protein intolerance (CMPI) is poorly recognized in preterm infants. This study examined the clinical events that preceded the diagnosis of CMPI in preterm infants. METHODS: This was a retrospective study of infants in a level-III neonatal intensive care unit of those who received parenteral nutrition (PN) support during a 12-month period. Parameters assessed included birth weight (g), diagnosis, duration and frequency on PN, type of enteral feeds at initiation, and achievement of enteral autonomy. CMPI was diagnosed based on persistent feeding intolerance that resolved after change of feeds from intact protein to a protein hydrolysate or crystalline amino acid formula. RESULTS: Three hundred forty-eight infants with birth weight (median/range) 1618 g (425-5110) received PN. Fifty-one (14%) infants required multiple courses of PN, and 19 of 348 (5%) were diagnosed with CMPI. The requirement for multiple courses on PN versus single course was associated with a high likelihood of CMPI: 14 of 51 versus 5 of 297, P < 0.001. Nine of the 14 infants identified with CMPI were initially diagnosed with necrotizing enterocolitis (NEC) after a median duration of 22 days (19-57) on intact protein feeds. After recovery from NEC, they had persistent feeding intolerance including recurrence of "NEC-like illness" (N = 3) that resolved after change of feeds to a protein hydrolysate or crystalline amino acid formula. CONCLUSIONS: The requirement for multiple courses of PN because of persistent feeding intolerance after recovery from NEC and recurrence of "NEC-like illness" may be a manifestation of CMPI in preterm infants.

Clinical features of Candidiasis in patients with inherited interleukin 12 receptor ß1 deficiency.

BACKGROUND: Interleukin 12Rß1 (IL-12Rß1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rß1 deficiency. RESULTS: Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. CONCLUSIONS: Patients who are deficient in IL-12Rß1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.

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.

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.

Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet.

OBJECTIVES: Eosinophilic esophagitis (EoE) is an immune-mediated chronic inflammatory disorder triggered by food antigen(s). A 6-food elimination diet (SFED) excluding cow's milk, soy, wheat, egg, peanuts/tree nuts, and seafood has been shown to induce remission in a majority of children with EoE. The goal of the present study was to identify specific food antigens responsible for eosinophilic esophageal inflammation in children with EoE who had achieved histological remission with the SFED. PATIENTS AND METHODS: In this analysis, we retrospectively analyzed children with EoE who completed subsequent single-food reintroductions that led to identification of foods causing disease recurrence. Repeat upper endoscopy with biopsies was performed after single-food introductions. Recurrence of esophageal eosinophilia following a food reintroduction identified that food antigen as a cause of EoE. RESULTS: A total of 36/46  (25 M/11F) children who were initially successfully treated with SFED completed this trial; the mean age was 7.6  ±  4.3 years. The most common foods identified were 25 to cow's milk (74%), 8 to wheat (26%), 4 to eggs (17%), 3 to soy (10%), and 1 to peanut (6%). Milk was 8 times more likely to cause EoE compared with wheat, the next most common food (95% confidence interval 2.41-26.62, P = 0.0007). CONCLUSIONS: Serial single-food reintroductions following induction of histological remission with the SFED can lead to the identification of specific causal food antigen(s) in EoE. Cow's milk was the most common food identified in subjects with EoE treated with SFED. A subset of children with EoE may develop tolerance to their food sensitivities while on the SFED.

Whole-blood-free choline and choline metabolites in infants who require chronic parenteral nutrition therapy.

BACKGROUND AND AIM: Choline deficiency is associated with hepatic dysfunction. Parenteral nutrition (PN) and lipid emulsions contain phosphatidylcholine (PtdCho) but insignificant free choline (FCho). PtdCho is sequentially degraded to glycerolphosphocholine (GPCho), phosphocholine (PCho), and finally to FCho. Biosynthesis of FCho may be insufficient during PN therapy. The aim of the study was to examine the status of FCho and related metabolites in infants on prolonged (> or =4 weeks) PN. METHODS: Whole blood concentrations of FCho, PtdCho, GPCho, and PCho were measured and compared in infants on PN and infants on enteral feeds (controls). RESULTS: Infants on PN (n = 14) had higher birth weight but same postnatal age as controls (n = 14) (mean +/- standard deviation) 8.3 +/- 3.9 versus 7.4 +/- 3.6 weeks. Parenteral nutrition was associated with increased PtdCho 1761 +/- 452 versus 1471 +/- 221 nmol/mL, P = 0.04. Mean whole blood FCho, GPCho, and PCho concentrations did not differ significantly in PN versus controls: 40.0 +/- 15.4 versus 50.8 +/- 49.7, 16.4 +/- 14.5 versus 25.2 +/- 29.3, and 15.3 +/- 13.5 versus 22.0 +/- 14.8 nmol/mL, respectively. However, PCho was positively correlated with GPCho in controls (r = 0.91, P < 0.01) but not PN (r = 0.24, P = NS), and infants receiving >90% of daily energy intake from PN (n = 6) had decreased PCho, 5.7 +/- 4.1 nmol/mL, compared with those receiving <90% of daily energy intake (n = 8) 22.5 +/- 13.7 nmol/mL, P < 0.05, and controls, 22.0 +/- 14.8 nmol/mL, P < 0.01. CONCLUSIONS: Decreased whole-blood concentrations of choline suggest possible evidence of choline deficiency as illustrated by decreased whole-blood PCho. Choline supplementation should be investigated in infants who require prolonged PN, and whole-blood PCho can be used to monitor response.

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.

Intestinal permeability and effects of Lactobacillus rhamnosus therapy in children with short bowel syndrome.

BACKGROUND: The present study was conducted to investigate the effects of Lactobacillus rhamnosus (also known as LGG) on intestinal permeability (IP) in children with short bowel syndrome (SBS). PATIENTS AND METHODS: In a double-blind, placebo-controlled crossover clinical trial, baseline IP (ie, lactulose-to-mannitol ratio) was measured in subjects with SBS and healthy control subjects. Subjects with SBS received LGG or placebo for 4 weeks, followed by a 3-week washout before therapy was crossed over for another 4 weeks. IP, quantitative fecal cultures for Lactobacillus species (in colony-forming units [cfu] per gram of stool) and hydrogen breath test (HBT) were performed during LGG and placebo phases of therapy. RESULTS: Twenty-one children (SBS, n = 9; control, n = 12) with a median age of 4.5 years (range 1.6-16.4 years) enrolled. Baseline IP measurements were similar in patients with SBS and control subjects: 0.08 +/- 0.06 (mean +/- SD) versus 0.07 +/- 0.05 (P = 1.0). IP was correlated with age in control subjects (r = -0.83, P = 0.001) but not among patients with SBS (r = -0.55, P = 0.16). Fecal colonization with Lactobacillus species did not differ during LGG versus placebo therapy (median 1.4 x 10(9) cfu/g [range 4.0 x 10(5) to 4.0 x 10(9) cfu/g] vs 6.0 x 10(9) cfu/g [1.0 x 10(3) to 1.0 x 10(10) cfu/g], respectively; P = 0.83). LGG therapy had no consistent effects on IP (P = 0.58) or its relationship with age (r = -0.40, P = 0.29), and was associated with conversion to positive HBT results in 1 subject. CONCLUSIONS: In this sample of children with SBS, the IP was within normal limits but did not correlate with age. LGG therapy had no consistent effects on IP. These findings do not support empiric LGG therapy to enhance IP in children with SBS.