Reflections on treatment of IBD in children and adolescents.

Major pharmaceutical advancements in the field of inflammatory bowel diseases benefit to children and adolescents affected with this progressive chronic condition. Scientific organisations such as ESPGHAN and ECCO actively publish guidelines related to the many aspects of care from these patients. Clinical studies and long-term prospective registries in the appropriate age groups are crucial to support an evidence based strategy.

Gastric Emptying of Liquids in Children.

OBJECTIVES: The present study was performed to determine normal values for gastric half-emptying time (t1/2GE) of liquids in healthy children. METHODS: Gastric emptying (GE) of a standardized test milk-drink measured with technetium scintigraphy and the C-acetate breath test (C-ABT) was compared in 19 children ages between 4 and 15 years with upper gastrointestinal symptoms. The C-ABT was subsequently used to determine normal values for GE of the same liquid test meal in 133 healthy children ages between 1 and 17 years. RESULTS: In the group of children with upper gastrointestinal symptoms, the results showed a significant correlation (r = 0.604, P = 0.0006) between t1/2GE measured with both techniques. In the group of healthy children, the results of t1/2GE showed that there was no influence of age, sex, weight, height, and body mass index on GE. CONCLUSIONS: Normal values for GE of a standardized test milk-drink in healthy children were determined with the C-ABT. This technique is considered reliable and is well accepted by the patients.

Paediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up.

OBJECTIVE: The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. METHODS: Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. RESULTS: At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. CONCLUSIONS: Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.

Fecal Microbiota Transplantation: Just a Fancy Trend?

The risks and advantages of the administration of fecal material of healthy people to patients are heavily debated. In adults, recurrent Clostridium difficile has become an accepted indication. In addition to all of the possible indications, many other questions need to be answered before pediatric indications and recommendations can be established. Optimal donor selection, fresh versus frozen stools versus capsules containing only microbiota, volume, and route of administration are just a few examples of the areas with missing data to allow in formulating recommendations for fecal microbiota or fecal material administration in children. A careful but not-too-complex regulation is the first priority in order to minimize the risk of administration of fecal slurry from unselected donors at home without medical supervision.

Safety and tolerance of a new extensively hydrolyzed rice protein-based formula in the management of infants with cow's milk protein allergy.

UNLABELLED: Guidelines recommend the use of extensively hydrolyzed cow's milk protein-based formulas (eHF) in the treatment of infants with cow's milk protein allergy (CMPA). Extensively hydrolyzed rice protein infant formula (eRHF) has recently become available and could offer a valid alternative. A prospective trial was performed to evaluate the hypo-allergenicity and safety of a new eRHF in infants with a confirmed CMPA. Patients were fed the study formula for 6 months. Clinical tolerance of the eRHF was evaluated with a symptom-based score (SBS) and growth (weight and length) was monitored. Forty infants (mean age, 3.4 months; range, 1-6 months) with CMPA confirmed by a food challenge were enrolled. All infants tolerated the eRHF and the SBS significantly decreased as of the first month of intervention. Moreover, the eRHF allowed a catch-up to normal weight gain as of the first month as well as a normalization of the weight-for-age, weight-for length, and BMI z-scores within the 6-month study period. CONCLUSION: In accordance with current guidelines, this eRHF was tolerated by more than 90 % of children with proven CMPA with a 95 % confidence interval. This eRHF is an adequate and safe alternative to cow milk-based eHF.

Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIMS: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.

Gastrointestinal manifestations of cow's milk protein allergy and gastrointestinal motility.

UNLABELLED: Cow's milk protein allergy (CMPA) may cause gastrointestinal motility disorders. Symptoms of both conditions overlap and diagnostic tests do not reliably differentiate between both. A decrease of symptoms with an extensive hydrolysate and relapse during challenge is not a proof of allergy, because hydrolysates enhance gastric emptying, a pathophysiologic mechanism of gastro-oesophageal reflux (GER). Thickened formula reduces regurgitation, and failure to do so suggests CMPA. A thickened extensive hydrolysate may induce more rapid improvement, but does not always differentiate between CMPA and GER. Different hypotheses are discussed: is the overlap between CMPA and functional disorders coincidence, or do both entities present with identical symptoms, or does the fact that symptoms are identical indicates that there is only one entity involved? Studies on the prevention of CMPA focused on 'at-risk families', and resulted in a decrease of CMPA and atopic dermatitis, but did not provide data on the incidence of GER. CONCLUSION: As long as there are no objective diagnostic tools to separate GER from CMPA, the physician has two options: first treat the most likely diagnosis, and switch if after 2-4 weeks there is no improvement, or treat both conditions with one intervention, what will not result in a diagnosis.

Soy infant formula: is it that bad?

UNLABELLED: The objective of this study is to review the indications of soy infant formula (SIF). Structured review of publications is made available through standard search engines (Pubmed,…). The medical indications for SIF are limited to galactosaemia and hereditary lactase deficiency. In the treatment of cow's milk allergy, SIF is used for economic reasons, as extensive hydrolysates are expensive. SIF is dissuaded mainly because of its phytooestrogen content. Isoflavone serum levels are much higher in SIF-fed infants than in breastfed or cow milk formula-fed infants. Administration of pure isoflavones to animals causes decreased fertility, but clinically relevant adverse effects of SIF in infants are not reported. CONCLUSION: Soy infant formula remains an option for feeding of term born infants if breastfeeding is not possible and if standard infant formula is not tolerated.

Plant-Based Formulas and Liquid Feedings for Infants and Toddlers.

Exclusive breastfeeding is the recommended feeding for all infants. Recent research has focused on the importance of balanced feeding during the first 1000 days, starting at conception with a balanced diet of the pregnant woman, up to the age of two years. The following step, a balanced diet after the age of two years is a challenge, as the dietary intake becomes more diversified. The role of young-child formula in this process is debated. This paper discusses the use of planted-based drinks, since they are a valuable and progressively more popular alternative for cow's milk, if nutritionally adapted to the requirements of toddlers. Plant-based drinks are per definition lactose free.

Long-term Outcomes with Anti-TNF Therapy and Accelerated Step-up in the Prospective Pediatric Belgian Crohn's Disease Registry (BELCRO).

BACKGROUND: Accelerated step-up or anti-tumor necrosis factor (TNF) before first remission is currently not recommended in pediatric Crohn's disease. METHODS: Five-year follow-up data from a prospective observational cohort of children diagnosed with Crohn's disease in Belgium were analyzed. Disease severity was scored as inactive, mild, or moderate to severe. Remission or inactive disease was defined as sustained if lasting ≥2 years. Univariate analyses were performed between anti-TNF-exposed versus naive patients and anti-TNF before versus after first remission and correlations assessed with primary outcomes average disease severity and sustained remission. RESULTS: A total of 91 patients (median [IQR] age 12.7 [10.9-14.8] yrs, 53% male) were included. Disease location was 12% L1, 23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement. Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF-exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated with age (13.1 [11.5-15.2] versus 11.8 [8.7-13.8] yrs; P < 0.05), L2 (29% versus 8%; P = 0.04), and average disease severity (1.7 [1.4-1.9] versus 1.4 [1.3-1.6]; P < 0.001). Duration of anti-TNF correlated with average disease severity (r = 0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 [12.1-15.9] versus 12.5 [10.2-14.1]; P = 0.02) and average disease severity (1.8 [1.6-1.9] versus 1.6 [1.3-1.8]; P = 0.002). Duration of sustained remission was similar in all patients, and no serious infections, cancer, or deaths were reported. CONCLUSIONS: Anti-TNF therapy and accelerated step-up in older patients with more severe disease leads to beneficial long-term outcomes.

Safety of a thickened extensive casein hydrolysate formula.

OBJECTIVES: Cow's milk allergy (CMA) is treated in formula-fed infants with an extensive protein hydrolysate. This study aimed to evaluate the nutritional safety of a non-thickened and thickened extensively casein hydrolyzed protein formula (NT- and T-eCHF) in infants with CMA. METHODS: Infants younger than 6 mo old with a positive cow milk challenge test, positive IgE, or skin prick test for cow milk were selected. Weight and length were followed during the 6 mo intervention with the NT-eCHF and T-eCHF. RESULTS: A challenge was performed in 50/71 infants with suspected CMA and was positive in 34/50. All children with confirmed CMA tolerated the eCHF. The T-eCHF leads to a significant improvement of the stool consistency in the whole population and in the subpopulation of infants with proven CMA. Height and weight evolution was satisfactory throughout the 6 mo study. CONCLUSIONS: The eCHF fulfills the criteria of a hypoallergenic formula and the NT- and T-eCHF reduced CMA symptoms. Growth was within normal range.

An extensively hydrolysed rice protein-based formula in the management of infants with cow's milk protein allergy: preliminary results after 1 month.

BACKGROUND: Guidelines recommend extensively hydrolysed cow's milk protein formulas (eHF) in the treatment of infants diagnosed with cow's milk protein allergy (CMPA). Extensively hydrolysed rice protein infant formulas (eRHFs) have recently become available, and could offer a valid alternative. METHODS: A prospective trial was performed to evaluate the clinical tolerance of a new eRHF in infants with a confirmed CMPA. Patients were followed for 1 month. Clinical tolerance of the eRHF was evaluated with a symptom-based score (SBS) and growth (weight and length) was monitored. RESULTS: Thirty-nine infants (mean age 3.4 months, range 0.5-6 months) diagnosed with CMPA were enrolled. All infants tolerated the eRHF and experienced a normal growth. CONCLUSIONS: In accordance with current guidelines, this eRHF is tolerated by more than 90% of children with proven CMPA with a 95% CI, and is an adequate alternative to cow's milk-based eHF. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01998074.

Prebiotics in infant formula.

The gastrointestinal microbiota of breast-fed babies differ from classic standard formula fed infants. While mother's milk is rich in prebiotic oligosaccharides and contains small amounts of probiotics, standard infant formula doesn't. Different prebiotic oligosaccharides are added to infant formula: galacto-oligosaccharides, fructo-oligosaccharide, polydextrose, and mixtures of these. There is evidence that addition of prebiotics in infant formula alters the gastrointestinal (GI) microbiota resembling that of breastfed infants. They are added to infant formula because of their presence in breast milk. Infants on these supplemented formula have a lower stool pH, a better stool consistency and frequency and a higher concentration of bifidobacteria in their intestine compared to infants on a non-supplemented standard formula. Since most studies suggest a trend for beneficial clinical effects, and since these ingredients are very safe, prebiotics bring infant formula one step closer to breastmilk, the golden standard. However, despite the fact that adverse events are rare, the evidence on prebiotics of a significant health benefit throughout the alteration of the gut microbiota is limited.

Treatment of Cow's Milk Protein Allergy.

The diagnosis and treatment of cow's milk protein allergy (CMPA) is still a challenge. A systematic literature search was performed using Embase, Medline, The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials for the diagnosis and treatment of cow's milk allergy (CMA). Since none of the symptoms of CMPA is specific and since there is no sensitive diagnostic test (except a challenge test), the diagnosis of CMPA remains difficult. A "symptom-based score" is useful in children with symptoms involving different organ systems. The recommended dietary treatment is an extensive cow milk based hydrolysate. Amino acid based formula is recommended in the most severe cases. However, soy infant formula and hydrolysates from other protein sources (rice) are gaining popularity, as they taste better and are cheaper than the extensive cow's milk based hydrolysates. Recent meta-analyses confirmed the safety of soy and estimate that not more than 10-15% of CMPA-infants become allergic to soy. An accurate diagnosis of CMA is still difficult. The revival of soy and the development of rice hydrolysates challenge the extensive cow's milk based extensive hydrolysates as first option and amino acid formula.

Probiotics and prebiotics in pediatric diarrheal disorders.

INTRODUCTION: In pediatrics, prebiotics and/or probiotics are added to infant formula, mainly to prevent diseases such as diarrheal disorders. Probiotic food supplements and medication are frequently used in the treatment of diarrheal disorders. This paper reviews the recent published evidence on these topics. AREAS COVERED: Relevant literature published using PubMed and CINAHL was collected and reviewed. Recent review papers were give special attention. EXPERT OPINION: The addition of pre- and/or probiotics to infant formula seems not harmful, but the evidence for benefit is limited. Most probiotics are commercialized as food supplements, and therefore do not qualify for medication legislation. Worldwide, Saccharomyces boulardii is the only strain which is registered as "medication" in the majority of countries. Efficacy data can only be considered if performed with the commercialized product. Some products reduce the risk for antibiotic-associated diarrhea and reduced the duration of acute infectious diarrhea with about 24 h. Overall, data in the other indications (inflammatory bowel disease, irritable bowel syndrome) are disappointing, although there are some recent promising results. The use of food supplements as medication opens the discussion to create a category of "medical food."

Probiotics and IBD.

The pathophysiology of inflammatory bowel disease is still incompletely understood. While the development of the immune system and the establishment of the microflora take place during infancy young patients often have a more severe and extensive disease. The differences in composition and concentration of intestinal microbiota and aberrant immune responses towards the luminal bacteria prompted the concept of an 'ecological' approach to control the disease course. Probiotics, living, non pathogenic micro organisms with a beneficial effect on the host, and prebiotics, oligosaccharides promoting the growth of the beneficial microflora, have been studied to this effect. Results have so far been disappointing for Crohn's disease but encouraging for ulcerative colitis. An overview of studies using probiotics in adults or children and a perspective on specific pediatric issues is provided in this review.