High hydrostatic pressure is similar to Holder pasteurization in preserving donor milk antimicrobial activity.

BACKGROUND: The microbiological safety of donor milk (DM) is commonly ensured by Holder pasteurization (HoP, 62.5 °C for 30 min) in human milk banks despite its detrimental effects on bioactive factors. We compared the antimicrobial properties of DM after Holder pasteurization treatment or High Hydrostatic Pressure processing (HHP, 350 MPa at 38 °C), a non-thermal substitute for DM sterilization. METHODS: We assessed lactoferrin and lysozyme concentrations in raw, HHP- and HoP-treated pools of DM (n = 8). The impact of both treatments was evaluated on the growth of Escherichia coli and Group B Streptococcus in comparison with control media (n = 4). We also addressed the effect of storage of HHP treated DM over a 6-month period (n = 15). RESULTS: HHP milk demonstrated similar concentrations of lactoferrin compared with raw milk, while it was significantly decreased by HoP. Lysozyme concentrations remained stable regardless of the condition. Although a bacteriostatic effect was observed against Escherichia coli at early timepoints, a sharp bactericidal effect was observed against Group B Streptococcus. Unlike HoP, these results were significant for HHP compared to controls. Stored DM was well and safely preserved by HHP. CONCLUSION: Our study demonstrates that this alternative sterilization method shows promise for use with DM in human milk banks. IMPACT: Antimicrobial activity of donor milk after High Hydrostatic Pressure treatment has not been clearly evaluated. Donor milk lactoferrin is better preserved by High Hydrostatic Pressure than conventional Holder pasteurization, while lysozyme concentration is not affected by either treatment. As with Holder pasteurization, High Hydrostatic Pressure preserves donor milk bacteriostatic activity against E. coli in addition to bactericidal activity against Group B Streptococcus. Donor milk treated by High Hydrostatic Pressure can be stored safely for 6 months.

Efficacy of vedolizumab and ustekinumab in pediatric-onset inflammatory bowel disease: A real-world multicenter study.

OBJECTIVES: Vedolizumab and ustekinumab are effective in inducing and maintaining corticosteroid-free clinical remission (CFR) in adult patients with inflammatory bowel disease (IBD). This study describes the efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. METHODS: All patients ≤18 years of age with Crohn's disease (CD) or ulcerative colitis (UC) treated with vedolizumab or ustekinumab in three centers in Northern France were followed retrospectively. The primary outcome was CFR at Week 14 (W14). RESULTS: Twenty-five patients (9 CD, 16 UC) and 33 patients (28 CD, 5 UC) were started on vedolizumab and ustekinumab respectively between 2016 and 2021. All were previously treated with antitumor necrosis factor (TNF). The median time from diagnosis to treatment initiation was 21.0 (12.0-44.0) and 42.0 (22.0-73.5) months for vedolizumab and ustekinumab respectively. Among vedolizumab-treated patients, 36% were in CFR at W14, including 22% in CD and 44% in UC. At W52, 56% were in CFR, including 33% in CD and 69% in UC. Among ustekinumab-treated patients, 49% were in CFR at W14, including 54% in CD and 20% in UC. At W52, 55% were in CFR, including 57% in CD and 40% in UC. There was a significant increase in median growth velocity between W0 and W52 of +2 SD in vedolizumab-treated patients (p = 0.0002). Four adverse events were reported during vedolizumab treatment, none for ustekinumab-treated patients. CONCLUSIONS: Vedolizumab and ustekinumab appear to be effective in inducing and maintaining CFR in pediatric-onset IBD. Randomized controlled trials are needed to confirm these results.

Donor human milk treated by high-pressure processing improves the body growth of growth-restricted mice pups.

INTRODUCTION: Pasteurized human donor milk (DM) is frequently used for feeding preterm newborns and extrauterine growth-restricted (EUGR) infants. Most human milk banks performed a pasteurization of DM using the standard method of Holder pasteurization (HoP) which consists of heating milk at 62.5°C for 30 min. High hydrostatic pressure (HHP) processing was proposed to be an innovative nonthermal method to pasteurize DM. However, the effect of different modes of DM pasteurization on body growth, intestinal maturation, and microbiota has never been investigated in vivo during the lactation. OBJECTIVES: We aimed to study these effects in postnatally growth-restricted (PNGR) mice pups daily supplemented with HoP-DM or HHP-DM. METHODS: PNGR was induced by increasing the number of pups per litter (15 pups/mother) at postnatal Day 4 (PND4). From PND8 to PND20, mice pups were supplemented with HoP-DM or HHP-DM. At PND21, the intestinal permeability was measured in vivo, the intestinal mucosal histology, gut microbiota, and short-chain fatty acids (SCFAs) level were analyzed. RESULTS: HHP-DM pups displayed a significantly higher body weight gain than HoP-DM pups during lactation. At PND21, these two types of human milk supplementations did not differentially alter intestinal morphology and permeability, the gene-expression level of several mucosal intestinal markers, gut microbiota, and the caecal SCFAs level. CONCLUSION: Our data suggest that HHP could be an attractive alternative to HoP and that HHP-DM may ensure a better body growth of preterm and/or EUGR infants.

Risk factors for surgery in stricturing small bowel Crohn's disease: A retrospective cohort study from the GETAID pédiatrique.

OBJECTIVES: Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. METHODS: Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. RESULTS: Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was 11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received  before stricture diagnosis included MODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection were antibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). CONCLUSION: In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.

Natural History of Anal Ulcerations in Pediatric-Onset Crohn's Disease: Long-Term Follow-Up of a Population-Based Study.

INTRODUCTION: Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. METHODS: All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. RESULTS: Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. DISCUSSION: Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration.

New Therapeutic Strategies Are Associated With a Significant Decrease in Colectomy Rate in Pediatric Ulcerative Colitis.

INTRODUCTION: We evaluated the impact of immunosuppressants (IS) and antitumor necrosis factor (TNF) introduction on long-term outcomes of ulcerative colitis (UC) in a large population-based pediatric-onset cohort. METHODS: All patients included in the EPIMAD registry with a diagnosis of UC made before the age of 17 years between 1988 and 2011 were followed up retrospectively until 2013. Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). RESULTS: A total of 337 patients (female, 57%) diagnosed with UC were followed up during a median duration of 7.2 years (interquartile range 3.8-13.0). The IS and anti-TNF exposure rates at 5 years increased over time from 7.8% (P1) to 63.8% (P3) and from 0% (P1) to 37.2% (P3), respectively. In parallel, the risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P -trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) ( P = 0.013). The risk of disease extension at 5 years remained stable over time (P1, 36%, P2, 32%, and P3, 34%; P = 0.31, P -trend = 0.52) and between the pre-anti-TNF era (P1 + P2, 34%) and the anti-TNF era (P3, 34%) ( P = 0.92). The risk of flare-related hospitalization at 5 years significantly increased over time (P1, 16%; P2, 27%; P3, 42%; P = 0.0012, P -trend = 0.0006) and between the pre-anti-TNF era (P1 + P2, 23%) and the anti-TNF era (P3, 42%) ( P = 0.0004). DISCUSSION: In parallel with the increased use of IS and anti-TNF, an important decline in the risk of colectomy in pediatric-onset UC was observed at the population level.

Validation of the IMPACT-III Questionnaire in French Children With Inflammatory Bowel Disease.

OBJECTIVES: This study assessed the reliability and validity of the IMPACT-III questionnaire, a health-related quality of life (HRQoL) instrument, in French children with inflammatory bowel disease (IBD). METHODS: Eighty-four children and adolescents (45 boys, aged 14.3 ± 2.7 years) were included in a validation study of the IMPACT-III questionnaire. Patients completed 2 questionnaires for measuring HRQoL: the IMPACT-III and the Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL). Internal consistency was assessed using Cronbach α. Factor analysis was performed on data from the IMPACT-III to help construct domains. Concurrent validity was assessed by calculating Spearman correlation coefficients. RESULTS: Cronbach α for the PedsQL total score was good (0.89). The most robust factor solution was a 3-domain structure: (a) Concerns, (b) Body Image and Physical Condition, and (c) Symptoms and Socializing. All domains had good reliability (0.674-0.863). Only 2 items had to be removed. Discriminant validity was demonstrated by significant differences ( P < 0.001) in median IMPACT-III scores between inactive and active disease for the total score (83.3 vs 72.0), and for Concerns ( P < 0.002) and Symptoms and Socializing ( P < 0.001). CONCLUSIONS: These results suggest that IMPACT-III appears to be a useful instrument for measuring HRQoL in French children with IBD.

Complications of one-step button percutaneous endoscopic gastrostomy in children.

To assess the complications of one-step button percutaneous endoscopic gastrostomy (B-PEG) and determine risk factors for developing stomal infections or gastropexy complications. A retrospective study of 679 children who underwent a B-PEG procedure in a single tertiary care center over a 10-year period to December 2020 was conducted. Patient characteristics, early complications (occurring ≤ 7 days after the procedure), late complications (> 7 days after the procedure), and outcomes were collected from medical records. A list of potential risk factors, including age at procedure, prematurity, underlying neurological disease, and undernutrition, was determined a priori. At least 1 year of follow-up was available for 513 patients. Median follow-up duration was 2.8 years (interquartile range 1.0-4.9 years). Major complications were rare (< 2%), and no death was related to B-PEG. Early complications affected 15.9% of the study population, and 78.0% of children presented late complications. Development of granulation tissue was the most common complication followed in frequency by tube dislodgment and T-fastener complications. Only 24 patients (3.5%) presented stomal infections. Young age at the time of PEG placement (odds ratio (OR) 2.34 [1.03-5.30], p = .042) was a risk factor for developing peristomal infection. T-fastener migration occurred in 17.3% of children, and we found underlying neurological disease was a protective factor (OR 0.59 [0.37-0.92], p = .019).  Conclusion: B-PEG is a safe method and associated with a low rate of local infection. However, T-fasteners are associated with significant morbidity and require particular attention in young and premature infants. What is Known: • Percutaneous endoscopic gastrostomy (PEG) is the preferred method to provide long-term enteral nutrition in children to prevent malnutrition. The Pull-PEG method is still the most commonly used with complications , such as stomal infection. Since its description, only a few studies have reported postoperative complications of one-step button PEG (B-PEG). What is New: • T-fastener complications were not rare, and underlying neurologic disease was a protective factor. A very low rate of stomal infection was described, and young age at the time of PEG placement was a risk factor. The B-PEG is a safe method with fewer major complications than P-PEG in children.

New Therapeutic Strategies Have Changed the Natural History of Pediatric Crohn's Disease: A Two-Decade Population-Based Study.

BACKGROUND & AIMS: We evaluated the impact of immunosuppressants (IS) and anti-tumor necrosis factor (TNF) introduction on Crohn's disease (CD) long-term outcomes in a large population-based, pediatric-onset cohort. METHODS: All patients included in the EPIMAD registry with a diagnosis of CD occurring when they were younger than age 17 years and between 1988 and 2011 were followed up retrospectively until 2013. Three diagnostic periods were defined: 1988 to 1993 (period [P]1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). Medication exposure and disease outcomes were compared between the 3 diagnostic periods. RESULTS: A total of 1007 patients diagnosed with CD were followed up for a median duration of 8.8 years (interquartile range, 4.6-14.2 y). The IS and anti-TNF exposure rate at 5 years increased over time from 33.9% (in P1) to 76.5% (in P3) and from 0% (in P1) to 50.5% (in P3), respectively. In parallel, the risk for intestinal resection at 5 years decreased significantly over time (P1, 35%; P2, 31%; and P3, 22%; P = .0003, Ptrend < .0001), and between the pre-anti-TNF era (P1 + P2, 32%) and the anti-TNF era (P3, 22%) (P = .0007). The risk for progression from inflammatory to stricturing behavior decreased significantly over time (P1, 27%; P2, 28%; and P3, 20%; P = .11, Ptrend = .041) and between the pre-anti-TNF era (P1 + P2, 28%) and the anti-TNF era (P3, 20%) (P = .040). The risk for a CD flare-related hospitalization at 5 years remained stable over time (P1, 31%; P2, 31%; and P3, 29%; P = .76, Ptrend = .53). CONCLUSIONS: In parallel with the increased use of IS and anti-TNF, positive changes in the natural history of pediatric-onset CD were observed at the population level. A decreased risk of both intestinal resections and stricturing complications were observed during the anti-TNF era.

Endoscopic Gastrojejunostomy in Infants and Children.

OBJECTIVE: To evaluate the feasibility of endoscopic gastrojejunal tube (GJT) placement in infants and children. STUDY DESIGN: All children undergoing endoscopic GJT placement between January 2010 and December 2019 were included in this single-center retrospective study. Difficulties with and failure of GJT placement, complication rates, and device longevity, efficacy, and duration were assessed. RESULTS: A total of 107 children, median age 10 months (IQR, 5.0-23.0 months) and median weight 6.6 kg (IQR, 5.3-9.5 kg), underwent endoscopic GJT placement using the gastric stoma to introduce the endoscope (one step: n = 36 of 107; 33.6%). Endoscopic placement was successful in 99%. Eight periprocedure complications occurred, including 1 pneumoperitoneum requiring exsufflation, 2 acute pulmonary hypertension episodes leading to death in 1 case, and 5 episodes of bronchospasm. Minor complications were frequent and mostly mechanical (79%), whereas major complications were rare (5.6%): intussusception (n = 4), intestinal perforation (n = 1), and pneumoperitoneum (n = 1). Ten patients died. Of the 97 patients who lived, 85 (87%) were weaned from jejunal feeding at a median of 179 days (IQR, 69-295 days) after initiation. Among them, 30 (35.2%) required fundoplication. Weight for age z-score was significantly higher at weaning. CONCLUSIONS: GJT placement is feasible in children, even low-weight infants. Complications are frequent but are mostly minor.

Prevalence of acid gastroesophageal reflux disease in infants with esophageal atresia/tracheoesophageal fistula.

BACKGROUND: Given the high prevalence and complication risks of acid gastroesophageal reflux (GERD) in the first months of life in infants with esophageal atresia, the ESPGHAN/NASPGHAN consensus statement recommends systematic treatment with proton pump inhibitors (PPIs) until the age of 1 year and checking for acid GERD thereafter. However, these recommendations have not been evaluated. METHODS: This prospective study was conducted from 2007 to 2016. We evaluated the prevalence of acid GERD in 100 consecutive infants presenting with esophageal atresia/tracheoesophageal fistula after the age of 18 months when PPI treatment was stopped. The diagnosis of acid GERD was based on positive pH-metry and/or evidence of complications (e.g., peptic esophagitis, need for jejunal nutrition, or antireflux surgery). Those with acid GERD at a median age of 18 months received a control examination every year or adapted to their clinical situation. RESULTS: The prevalence rates of acid GERD were 64.3% at 18 months and 22.8% at the last follow-up (median age 65 months).There is no risk factor for acid GERD identified. CONCLUSIONS: This study shows a high prevalence of acid GERD in late infancy and supports the recommendation of systematic checking for acid GERD when treatment with PPI is stopped. IMPACT: Acid gastroesophageal reflux disease (GERD) is a frequent complication of esophageal atresia in infants. The ESPGHAN/NASPGHAN consensus, which is based on expert opinion, recommends systematic treatment of children with PPI until the age of 1 year. The prevalence rates of acid GERD were 64.3% at 18 months and 22.8% at the last follow-up. This study shows a high prevalence of acid GERD in late infancy and supports the recommendation of systematic checking for acid GERD when treatment with PPI is stopped.

Iodine supplementation: is there a need?

PURPOSE OF REVIEW: To review the recent data on iodine deficiency, the impact of iodine deficiency on health outcomes and the need for iodine supplementation in at-risk populations, that is, pregnant and lactating women, infants and young children. RECENT FINDINGS: The 2019 Iodine Global Network Annual Report highlighted that only 23 countries worldwide (including Finland, Germany, and Norway in Europe) were classified as having insufficient iodine intake in 2019, down from 54 in 2003 and 113 in 1993. Even if severe iodine deficiency during pregnancy has a negative impact on cognitive outcomes later in life, the consequences of mild-to-moderate iodine deficiency on child neurodevelopment are controversial. Two 2017 and 2019 Cochrane Systematic Reviews found no evidence that iodine supplementation in women before, during or after pregnancy improved infant and child cognitive development in areas with mild-to-moderate iodine deficiency. Likewise, a 2019 Cochrane systematic review concluded that there was no evidence of a positive impact of iodine supplementation on morbidity, including cognitive impairment, and mortality in preterm infants. SUMMARY: There is no scientific evidence to support generalized iodine supplementation in mildly to moderately deficient settings not only in pregnant and lactating women but also in infants, either preterm or term, and in young children.

Daily physical activity patterns in children and adolescents with inflammatory bowel disease.

BACKGROUND: The aim of this study was to assess PA patterns among children and adolescents with inflammatory bowel disease (IBD). METHODS: Sixty participants with IBD (42 Crohn's disease [CD], 10 ulcerative colitis [UC], and 8 IBD-unclassified [IBD-U], 30 male patients) in remission (n = 45) or with mild disease (n = 15) were compared with 60 healthy age- and sex-matched controls. Each participant wore a triaxial accelerometer during 4 consecutive days for objective daily PA quantification. RESULTS: Overall, there was no significant difference in daily PA patterns between patients with IBD and healthy controls, with 31.7% of patients with IBD and 38.3% of healthy controls fulfilling the recommendation of 60 min of moderate-to-vigorous physical activity (MVPA) daily (NS). Male patients with IBD spent significantly less time in MVPA compared with matched healthy controls (mean difference, 16.2 min day-1; p < 0.05). No difference was observed for female patients with IBD. No difference in sedentary pattern between male patients with IBD and controls was found. CONCLUSIONS: Children and adolescents with inactive or mildly active IBD have similar PA patterns compared with healthy controls, except for male patients who have reduced moderate-to-vigorous PA. By far, most patients with IBD do not fulfill the MVPA recommendations for health benefits. IMPACT: There is few data on PA patterns in pediatric patients with IBD. Methodological issues to assess PA limit the strengths of these studies. Pediatric IBD patients with inactive or mildly active IBD have similar physical activity patterns compared with healthy controls, except for male patients who have reduced moderate-to-vigorous PA. Most patients with IBD do not fulfill the MVPA recommendations for health benefits.

Comparison of Symptom Control in Pediatric Gastroparesis Using Endoscopic Pyloric Botulinum Toxin Injection and Dilatation.

OBJECTIVES: The objective of this study was to assess the tolerance and efficacy of endoscopic intrapyloric botulinum toxin injection compared with pyloric dilatation in children with gastroparesis. METHODS: This was a retrospective descriptive multicentre study that included pediatric patients treated between 2010 and 2018 at 4 tertiary hospitals. RESULTS: Data were collected for 24 patients. The median age at diagnosis was 2.5 years (range 0.5-4.7). A total of 46 endoscopic procedures were performed. The endoscopic procedure was multiple in 63% of patients. Among the interventions, 76% were successful and 15% were unsuccessful. The recurrence rate was 57% and the median time to recurrence was 3.7 months (0.1-73). The efficacy did not differ significantly between the 2 methods at the first intervention and as a second-line treatment. The recurrence rate also did not differ significantly between the 2 methods. No complications were reported. The median follow-up was 19.8 months (1.7-61.7). CONCLUSIONS: In this retrospective multicentre study, endoscopic management of gastroparesis by balloon dilatation or botulinum toxin was safe in children and seemed to be partially efficient within the first months. Symptoms recurred frequently and required repetition of the interventions.

Factors Associated With Success and Failure of Weaning Children From Prolonged Enteral Nutrition: A Retrospective Cohort Study.

OBJECTIVES: The aims of the present study were to assess the efficacy of a tube weaning program, and to identify factors associated with success and failure. METHODS: This was a retrospective cohort study including all pediatric patients on enteral nutrition (EN) for ≥6 months for whom at least 1 attempt of weaning was performed in a single tertiary referral center from 2012 to 2017, with a minimum follow-up of 6 months after EN discontinuation. Weaning program was individualized to each child. Weaning success was defined a priori. Factors associated with success were investigated using multivariate analysis. RESULTS: Ninety-four patients were enrolled, in whom a total of 114 attempts of weaning were performed at a median age of 51 ±â€Š40 months. Success was achieved in 80 attempts (success rate of 70%). One hundred three (92%) weaning attempts were performed at home with a follow-up in the outpatient clinic, mostly (74%) by a progressive (>1 month) reduction of tube feeding. Patients who required psychological support during weaning had more failures than patients who did not (odds ratio = 5.7, 95% confidence interval [1.2-27.0], P = 0.03). The presence of impaired oral feeding skills at the time of EN discontinuation was also predictive of failure (odds ratio = 6.2, 95% confidence interval [0.05-0.5], P = 0.005). CONCLUSIONS: Our progressive, mostly outpatient-based, patient-tailored program of weaning from EN is effective for tube-dependent children. Children who need psychological support during weaning and those who present impaired oral feeding skills represent a subgroup of at-risk patients for whom alternative weaning strategies may need to be considered.

Efficacy and Safety of the Local Application of Mitomycin C to Recurrent Esophageal Strictures in Children.

OBJECTIVES: Research on long-term use of mitomycin C (MC) for recurrent esophageal stenoses is limited. We assessed the long-term efficacy and safety of local application of MC for recurrent esophageal stenoses in children. METHODS: This was a retrospective study of 39 patients (17 girls) with a median age of 19.5 months (range: 2.4-196.0) at the time of MC application. The etiologies of stenosis were esophageal atresia (n = 25), caustic ingestion (n = 9), congenital esophageal stenosis (n = 3), and other causes (n = 2). Stenosis was single in 35 (90%) patients and multiple in 4 (10%). Before MC, patients underwent multiple repeated dilations (median: 3 dilations per child [range: 2-26]) over a median period of 7 months (range: 2.6-49.3). Treatment success was defined a priori as a reduction in the number of dilations over the same period from before to after the application of MC. RESULTS: For 26 (67%) patients, the application of MC was considered a success: 102 versus 17 dilatations (P < 0.0001). Sixteen (41%) patients never required additional dilation during the follow-up after MC application (median: 3.1 years [range: 0.6-8.5]). No complication related to MC was observed. Biopsies at the site of MC application were performed at maximal follow-up in 16 patients and revealed no dysplasia. Three factors were associated with success of MC: single stenosis, short stenosis, and esophageal atresia type III. CONCLUSIONS: This study is the largest series reported showing that topical application of MC is an efficient and safe treatment for recurrent esophageal stenosis in children.

Experience of Using a Semielemental Formula for Home Enteral Nutrition in Children: A Multicenter Cross-sectional Study.

OBJECTIVES: The use of semielemental diets concerns a small proportion of children on enteral nutrition whose characteristics have never been reported. Our aim was to describe a cohort of patients on home enteral nutrition with Peptamen Junior, including the tolerance and nutritional efficacy of this product. METHODS: We performed a retrospective multicenter survey on a cohort of patients receiving this semielemental diet at home between 2010 and 2015 in 14 tertiary pediatric French centers. We recorded at baseline, 3, 6, and 12 months, and then every year the anthropometric characteristics of the patients, indications and modalities of administration of the diet, and the tolerance and adverse events. RESULTS: We recruited 136 patients ages 9.8 ±â€Š4.4 years at baseline. Mean body mass index z score was -1.0 ±â€Š1.8; mean height z score was -1.1 ±â€Š1.9. The main underlying diseases were digestive (35.3%), neurological (33.1%), and hematological (19.9%). The indications for a semielemental diet were failure of another diet in 70 patients (51.9%), severe malnutrition in 19 (14.1%), cystic fibrosis in 11 (8.1%), and switch from parenteral nutrition in 11 (8.1%). Side effects were observed in 39.2% of the patients, and required medical attention in 8.2%. Body mass index improved or remained normal in 88.3% of children. CONCLUSIONS: This semielemental diet seems to be well tolerated and efficient in the setting of home enteral nutrition in children with complex diseases featuring malabsorption and/or after failure of polymeric diet.

Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents.

OBJECTIVES: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. METHODS: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. RESULTS: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/105 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/105 (+126%; P<0.001) and for UC, from 1.6 to 4.1/105 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. CONCLUSIONS: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Growth Pattern in Paediatric Crohn Disease Is Related to Inflammatory Status.

OBJECTIVES: The respective role of disease activity and steroid therapy in growth impairment in paediatric-onset Crohn disease (CD) is still debated. Our aim was to investigate whether the growth pattern of children with CD was correlated with the inflammatory status during the disease course, regardless the cumulative duration of steroid therapy. METHODS: One hundred and seven patients with a diagnosis of CD <17 years, followed during ≥2 years and for whom ≥2 height measures were available during follow-up, were identified between 1998 and 2010. Height, C-reactive protein (CRP), orosomucoid, and steroid therapy duration were collected at each visit. The relationship between the evolution of growth velocity and inflammatory status during follow-up was investigated using a linear mixed model with random coefficients. RESULTS: Median age at diagnosis was 11.7 years (Q1-Q3: 9.8-13.5). Mean height for age (H/A) z score was 0.14 ±â€Š1.29 at diagnosis and 0.05 ±â€Š1.23 among the 75 patients who had reached their final height at maximal follow-up (median: 4.9 years; Q1-Q3: 3.8-6.4). Growth failure (H/A z score <-2) was present in 7 (8%) patients at diagnosis and 5 (5%) at maximal follow-up. Growth velocity was negatively correlated with the evolution of CRP (P < 0.0001) and orosomucoid (P < 0.0001) during follow-up. After adjustment for the cumulative duration of steroid therapy, these 2 correlations remained significant (CRP: P = 0.0008; orosomucoid: P < 0.0001). CONCLUSIONS: Children with CD with uncontrolled inflammatory status have a lower growth velocity. The inflammatory status should be kept as close to normal as possible in paediatric-onset patients with CD to optimize their growth pattern.

Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study.

BACKGROUND: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. METHODS: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. RESULTS: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. CONCLUSION: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.