Recognizing and addressing atypical growth.

While child growth evaluation is fundamental to paediatric practice, an increasingly complex clinical picture can complicate interpretation of growth patterns. This practice point uses representative case studies to illustrate key features of interpretation and response to commonly encountered growth patterns. Awareness of these common patterns and their etiologies will enhance the clinician's ability to respond appropriately and minimize the risk for under- or over-diagnosis of growth impairment.

Mechanical Complications in Central Lines Using Taurolidine Versus Ethanol Lock Therapy in Children With Intestinal Failure.

OBJECTIVES: Ethanol lock therapy (ELT) is effective in reducing rates of catheter-related-bloodstream infections (CRBSI) in the pediatric intestinal failure (IF) population; however, ELT may increase the risk of line occlusion and breakage, significantly impacting preservation of vascular access. During a period of ethanol shortage, Health Canada temporarily approved the use of taurolidine lock therapy (TLT) in pediatric iF patients previously utilizing ELT. This provided a unique opportunity to directly compare rates of central venous catheter (CVC) complications, including CRBSi, breaks, occlusions, repairs and replacements in patients who utilized both ELT and TLT. METHODS: A retrospective study of pediatric IF patients managed by three Western Canadian intestinal rehabilitation programs was performed. Event rates in patients who used both ELT and TLT during the study period were compared using Poisson regression analysis. RESULTS: In 13 patients with 10,187 catheter days (CDs), TLT (vs ELT) had lower rates of CVC breaks (1.11 vs 5.19/1000 CDs, P < 0.001), occlusions (0.83 vs 4.06/1000 CDs, P  = 0.01) and repairs (1.94 vs 5.64/1000 CDs, P  = 0.01). There was no difference in CRBSI rates (0.83 vs 2.03/1000 CDs, P  = 0.25) or rates of CVC replacements due to mechanical events (0.28 vs 1.81/1000 CDs, P  = 0.08). CONCLUSIONS: Although there was no difference in CRBSI rates, TLT was associated with lower rates of mechanical complications compared to ELT in this study. Taurolidine may be a suitable alternative to ethanol in preventing CRBSI and may be associated with improved preservation of central lines in children with IF.

Urine sodium to urine creatinine ratio as a marker of total body sodium in infants with intestinal failure.

PURPOSE: Urine sodium (UNa) is a measure of total body sodium in infants with intestinal failure (IF) but can be misleading as it does not reflect volume status. Urine sodium to urine creatinine ratio (UNa:UCr) may offer a more accurate measure, but is not routinely used. This study compares UNa:UCr to UNa as a maker of sodium status in infants with IF. METHODS: A retrospective review of infants with IF, from a single center, from 2018 to 2020 was conducted (REB H20-00,816). IF etiology, intestinal anatomy, nutritional intake, urine electrolytes and anthropometrics were collected. Linear mixed effects models adjusting for repeated measures were used to associate UNa and UNa:UCr with weight gain and sodium intake. RESULTS: Twenty-two infants with a median gestational age of 31 weeks were included. IF etiology included gastroschisis (41%), necrotizing enterocolitis (23%), and intestinal perforation (14%). Infants had an average of 3 paired UNa and UNa:UCr measures for a total of 74 paired measurements. UNa:UCr more strongly correlated with sodium intake compared to UNa (R = 0.25, p = 0.032 vs. R = 0.10, p = 0.38). Overall, neither UNa (p = 0.21) nor UNa:UCr (p = 0.16) were significantly correlated with weight gain. However, for infants receiving ≤50% nutrition enterally, weight gain correlated with UNa (p = 0.01) and UNa:UCr (p = 0.01). UNa:UCr >35 predicted adequate growth regardless of enteral intake (92% sensitivity, 59% specificity). CONCLUSION: UNa:UCr is a measure of total body sodium that correlates with sodium intake in infants with IF. Our study indicates UNa:UCr >35 is associated with adequate growth and can be used to guide further validation studies.

The Importance of the ileocecal valve and colon in achieving intestinal independence in infants with short bowel syndrome.

PURPOSE: Infants with short bowel syndrome (SBS) wean from parenteral nutrition (PN) support at variable rates. Small bowel length is a predictor, but the importance of the ileocecal valve (ICV) and colon are unclear. We aim to determine if the ICV and/or colon predict enteral autonomy. METHODS: Infants from a single intestinal rehabilitation program were retrospectively reviewed. Etiology of SBS, intestinal anatomy, and duration of nutritional support were collected for three years. The primary outcome was time to full enteral nutrition. ANCOVA and Cox proportional hazards model were used, with p < 0.05 significant. RESULTS: 55 infants with SBS were included. After accounting for the effect of small bowel, PN duration was shorter for infants with the ICV compared to those without (mean 218 vs. 538 days, p = 0.003), and had a more significant effect on infants with ≤50% of small bowel. Increased small bowel length was a positive predictor of weaning. Patients with ≤50% of colon spent less time on PN with the ICV, compared to without (mean 220 vs 715 days, p = 0.009). CONCLUSIONS: Preservation of the ICV was associated with shorter duration of PN support, while colon was not. Small bowel length is a positive predictor of enteral autonomy. LEVEL OF EVIDENCE: Level III retrospective comparative study TYPE OF STUDY: Retrospective review.

NeoCHIRP: A model for intestinal rehabilitation in the neonatal intensive care unit.

Multidisciplinary intestinal rehabilitation (IR) teams have transformed care in pediatric intestinal failure (IF).1 Although most children with IF are identified in the neonatal intensive care unit (NICU), IR teams may not be involved at this stage. We describe our collaborative model, blending NICU and IR expertise to optimize care. Over 6 years, the NeoCHIRP (Neonatal Children's IR Program) team followed 164 babies for weekly visits (median, 8; range, 1-27). Bedside rounds included CHIRP team physician and surgeons, neonatologist champion, attending neonatologist and fellow, NICU dietitian, bedside nurse, and family. Medical and nutrition status, nutrition history, and laboratory data were discussed, and a nutrition plan to support IR, considering the child's other medical needs, was created to guide the next week's management. Typical issues addressed included parenteral nutrition (PN) composition, enteral nutrition plan, oral feeding, management of small-intestinal bacterial overgrowth and sodium status, and cholestasis. A total of 164 babies were followed by the NeoCHIRP team. Of 153 survivors, IF resolved by discharge in 89% (136 of 153). Seventeen of 153 babies (11%) went on to require home PN and were transferred from NICU directly to the CHIRP team. By discharge, 99% of babies were orally fed (69/136, 50% fully, 67/136, 49% partially), and cholestasis improved or resolved in 80/105 (76%). Eleven babies (7%) died; four deaths were unrelated to IF, but in seven babies, IF was at least a contributing factor. In this high-risk cohort, most babies achieved good outcomes, and those who required longer-term IR transitioned smoothly to the CHIRP team.

Use of instructional videos to reduce central venous catheter complications in children with intestinal failure receiving home parenteral nutrition.

BACKGROUND: Children with intestinal failure (IF) require parenteral nutrition (PN) at home, delivered through a central venous catheter (CVC) to support growth. CVC-related complications including infection, breakage, and blockage are the most common cause of readmission to the hospital. The objective of this study was to evaluate the use of instructional videos as part of the caregiver home PN-teaching program to reduce CVC-related complications. METHODS: Caregivers of children with IF requiring home PN were surveyed to assess skill confidence and interest in instructional videos for skill acquisition. Videos were then created using a smartphone and free video-editing software. Input from stakeholders (families, care providers) was incorporated in video production. Families were given access to the videos, and CVC-related complications were compared for 2 years prior to and 1 year following video introduction with Welch t-test analysis. RESULTS: After obtaining ethics approval, 11 caregivers were surveyed. Thirty percent reported feeling underconfident in their skills at the time of discharge. After viewing the videos, 100% of caregivers reported that these videos were useful. Catheter-related complication rates significantly decreased in the year following the video introduction from 7.88 to 2.65 complications per 1000 catheter days (P = .046). This included reductions in catheter-related infections, catheter occlusions, and breakages. CONCLUSIONS: Children with IF receiving home PN are at high risk for CVC-related complications, and caregivers are the first line of defense for catheter care. Instructional videos were low-cost to create, were well received by all families, and may contribute to reduced catheter-related complications.

Long-Term Follow-up of Hypophosphatemic Bone Disease Associated With Elemental Formula Use: Sustained Correction of Bone Disease After Formula Change or Phosphate Supplementation.

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus (R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution (R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation.

Nutritional evaluation of the neurologically impaired child.

Nutrition is of key importance in optimizing function and health in children with neurological impairment. Challenges in quantifying individual needs and assessing nutritional status are barriers to determining the nutritional prescription. This practice point addresses common questions faced by clinicians caring for this population and uses available evidence to provide strategies to address these challenges.

Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children.

OBJECTIVE: Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. METHODS: A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. RESULTS: Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. CONCLUSION: The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop.

Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure.

BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure. METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year. RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in z scores and citrulline levels; the z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued. CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial.

BACKGROUND: Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. OBJECTIVE: The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. METHODS: Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. RESULTS: Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. CONCLUSIONS: ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.

A simplified trauma triage system safely reduces overtriage and improves provider satisfaction: a prospective study.

BACKGROUND: Standard triage systems result in high rates of overtriage to achieve acceptably low undertriage. We previously validated optimal triage variables and used these to implement a new simplified triage system (NEW) at our hospital. METHODS: All trauma entries from May 2010 to Feb 2013 were prospectively reviewed. Calculation of the undertriage and overtriage rates was based on the need for any urgent or life-saving intervention. RESULTS: We identified 704 trauma patients. Level 1 activations were reduced from 32% (OLD) to 19% in the NEW system (P < .05). Overtriage was reduced from 79% (OLD) to 44% in the NEW system (P < .01). The undertriage rate was 1.6% in the NEW system, compared with 1.2% in the OLD system (P = nonsignificant). Of all patients, 14% (63) required a life-saving intervention. There were no deaths among undertriaged patients. CONCLUSION: The NEW simplified triage system significantly reduced the rate of overtriage, while safely maintaining a low undertriage rate.

Mucous fistula refeeding in neonates with enterostomies.

BACKGROUND/PURPOSE: Neonates with intestinal pathology may require staged surgery with creation of an enterostomy and mucous fistula (MF). Refeeding (MFR) of ostomy output may minimize fluid and electrolyte losses and reduce dependence on parenteral nutrition (PN), though a paucity of evidence exists to support this practice. The purpose of this study was to assess the outcomes of infants undergoing MFR and document associated complications. METHODS: With REB approval, infants with intestinal failure undergoing MFR between January 2000 and December 2012 were identified. A chart review was conducted and relevant data were collected. Descriptive statistics were used. RESULTS: Twenty-three neonates underwent MFR. Mean gestational age and birth weight were 35weeks and 2416grams. Pathologies included intestinal atresia (n=12), necrotizing enterocolitis (n=5), meconium ileus (n=4), and other (n=6). Seven patients were able to wean from PN. Four patients had complications: 3 had perforation of the MF, 1 had bleeding. Four patients died, with one death directly attributable to MFR. CONCLUSIONS: In this cohort MF refeeding was associated with significant complications and ongoing PN dependence. With advances in intestinal rehabilitation and PN, the benefit of MF refeeding must be weighed against the potential complications.

Concentrations of lead, cadmium and barium in urban garden-grown vegetables: the impact of soil variables.

Paired vegetable/soil samples from New York City and Buffalo, NY, gardens were analyzed for lead (Pb), cadmium (Cd) and barium (Ba). Vegetable aluminum (Al) was measured to assess soil adherence. Soil and vegetable metal concentrations did not correlate; vegetable concentrations varied by crop type. Pb was below health-based guidance values (EU standards) in virtually all fruits. 47% of root crops and 9% of leafy greens exceeded guidance values; over half the vegetables exceeded the 95th percentile of market-basket concentrations for Pb. Vegetable Pb correlated with Al; soil particle adherence/incorporation was more important than Pb uptake via roots. Cd was similar to market-basket concentrations and below guidance values in nearly all samples. Vegetable Ba was much higher than Pb or Cd, although soil Ba was lower than soil Pb. The poor relationship between vegetable and soil metal concentrations is attributable to particulate contamination of vegetables and soil characteristics that influence phytoavailability.

The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study: rationale and methods.

The Alberta Pregnancy Outcomes and Nutrition (APrON) study is an ongoing prospective cohort study that recruits pregnant women early in pregnancy and, as of 2012, is following up their infants to 3 years of age. It has currently enrolled approximately 5000 Canadians (2000 pregnant women, their offspring and many of their partners). The primary aims of the APrON study were to determine the relationships between maternal nutrient intake and status, before, during and after gestation, and (1) maternal mood; (2) birth and obstetric outcomes; and (3) infant neurodevelopment. We have collected comprehensive maternal nutrition, anthropometric, biological and mental health data at multiple points in the pregnancy and the post-partum period, as well as obstetrical, birth, health and neurodevelopmental outcomes of these pregnancies. The study continues to follow the infants through to 36 months of age. The current report describes the study design and methods, and findings of some pilot work. The APrON study is a significant resource with opportunities for collaboration.

Prospective cohort study of the outcome of and risk factors for intravascular catheter-related bloodstream infections in children with intestinal failure.

BACKGROUND: Children with intestinal failure (IF) have frequent catheter-related bloodstream infections (CRBSIs). The purpose of this study was to prospectively study the clinical course of CRBSIs and to seek modifiable risk factors for CRBSIs in children with IF. MATERIALS AND METHODS: Children with IF were enrolled prospectively and data on potential risk factors collected monthly. Additional data were collected when they had CRBSIs. RESULTS: Sixteen children were enrolled, yielding 223 months of data. The rate of CRBSIs was 4.6 per 1000 catheter days. The most consistent symptom at onset of CRBSI was fever (28 of 32 cases). Elevated C-reactive protein (CRP) was the only laboratory abnormality that was consistently associated with the onset of CRBSI (elevated in 15 of the 18 cases where it was measured). Combining all episodes in the cases that relapsed, the catheter salvage rate was 17 of 29 (59%), including 4 of 11 polymicrobial CRBSIs. Risk factors for CRBSI included double lumen tunneled central venous catheter (CVC), jugular placement of CVC, higher doses of intralipid, and having <50 cm small bowel postresection. CONCLUSION: The diagnosis of CRBSI should be questioned in the absence of fever and/or elevated CRP. Salvage of catheters should be attempted with all bacterial CRBSIs, assuming that the child is stable since the CVC can be retained in the majority of cases.

A randomized, double-blind, placebo-controlled clinical trial of megestrol acetate as an appetite stimulant in children with weight loss due to cancer and/or cancer therapy.

BACKGROUND: Megestrol acetate (MA) is an appetite stimulant with efficacy in promoting weight gain in adults with cancer-associated anorexia-cachexia. Studies documenting MA efficacy in children, however, are limited. We present the first randomized, double-blind, placebo-controlled clinical trial of MA versus placebo in children with cancer and weight loss. METHODS: Subjects <18 years of age with weight loss (minimum 5% from highest previous weight; or %ideal body weight <90%) due to cancer and/or cancer therapy were randomized to either MA (7.5 mg/kg/day) or placebo for a planned study duration of 90 days. Primary outcome was the difference between groups in mean percent weight change from beginning to end of the study period. Secondary outcomes included effects on anthropometrics, body composition, need for tube feeding or parenteral nutrition, and toxicities. RESULTS: Twenty-six patients were randomly assigned (13 MA, 13 placebo). The MA group experienced a mean weight gain of +19.7% compared to a mean weight loss of -1.2% in the placebo group, for a difference of +20.9% (95%CI: +11.3% to +30.5%, P = 0.003) in favor of MA over placebo. MA subjects experienced significant increases in weight for age z-scores, body mass index z-scores, and mid upper arm circumference compared to placebo. DXA scanning suggested disproportionate increases in fat accrual. Adrenal suppression was the main toxicity of MA. CONCLUSION: In children with high-risk malignancies, MA resulted in significant increases in mean percent weight change compared to placebo. Further studies of MA should be pursued to better delineate the effect on nutritional status.

Caring for children with phenylketonuria.

OBJECTIVE: To provide an overview of the diagnosis and management of phenylketonuria (PKU) in childhood with an emphasis on aspects relevant to family physicians providing ongoing care. SOURCES OF INFORMATION: The author's experience as the clinic physician in a regional pediatric PKU clinic is supplemented with references providing evidence for key points. MAIN MESSAGE: While metabolic clinics typically provide guidance regarding the specific management of PKU, the family doctor has an essential role in providing ongoing medical care. CONCLUSION: Children and families have much to gain from strong relationships with family doctors, and family doctors can confidently provide care with awareness of the very few potential special needs of patients with PKU.