Partially Hydrolysed Whey-Based Infant Formula Improves Skin Barrier Function.

Specific partially hydrolysed whey-based infant formulas (pHF-W) have been shown to decrease the risk of atopic dermatitis (AD) in infants. Historically, AD has been associated primarily with milk allergy; however, defective skin barrier function can be a primary cause of AD. We aimed to ascertain whether oral supplementation with pHF-W can improve skin barrier function. The effect of pHF-W was assessed on transepidermal water loss (TEWL) and antibody productions in mice epicutaneously exposed to Aspergillus fumigatus. Human primary keratinocytes were stimulated in vitro, and the expression of genes related to skin barrier function was measured. Supplementation with pHF-W in neonatal mice led to a significant decrease in TEWL and total IgE, but not in allergen-specific antibody levels. The whey hydrolysate was sufficient to decrease both TEWL and total IgE. Aquaporin-3 gene expression, linked with skin hydration, was modulated in the skin of mice and human primary keratinocytes following protein hydrolysate exposure. Skin barrier improvement may be an additional mechanism by which pHF-W may potentially reduce the risk of AD development in infants. Further human studies are warranted to confirm the clinical efficacy of these observations.

Human Milk Bioactives: Future Perspective.

Human milk is a dynamic, complex fluid that offers much more than nutrition to infants. The macronutrient content of human milk has been well characterized and described. However, human milk is not a simple matrix of protein, carbohydrate, fat, and micronutrients. The National Institutes of Health have defined bioactives in food as elements that "affect biological processes or substrates and hence have an impact on body function or condition and ultimately health." Bioactives are cells, anti-infectious and anti-inflammatory agents, growth factors, and prebiotics that are naturally present in human milk. They may explain the differences in health outcomes observed between breastfed and non-breastfed infants. They influence the development of the immune and gastrointestinal systems, gut microbiota, neurodevelopment, metabolic health, and protection against infection. Human milk oligosaccharides are one bioactive that have been an increasingly popular area of research. This review provides a broad overview of some bioactive components that positively affect the immune system and touches on certain well-known growth factors present in human milk. Future research will look at the interplay of the multitude of bioactive components in human milk as a biological system and beyond singular compounds.

Hidden Realities of Infant Feeding: Systematic Review of Qualitative Findings from Parents.

A growing, global conversation, regarding realities and challenges that parents experience today is ever-present. To understand recent parent's attitudes, beliefs, and perceptions regarding infant feeding, we sought to systematically identify and synthesize original qualitative research findings. Following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) framework, electronic databases were searched with a priori terms applied to title/abstract fields and limited to studies published in English from 2015 to 2019, inclusive. Study quality assessment was conducted using the Critical Appraisal Skills Programme (CASP) checklist, and thematic analyses performed. Of 73 studies meeting inclusion criteria, four major themes emerged. (1) Breastfeeding is best for an infant; (2) Distinct attitudes, beliefs, and perceptions of mothers that breastfeed, and those that could not or chose not to breastfeed, are evident; (3) Infant feeding behaviors are influenced by the socio-cultural environment of the family, and (4) Parent's expectations of education and support addressing personal infant feeding choices from health care providers are not always met. This systematic review, guided by constructs within behavioral models and theories, provides updated findings to help inform the development of nutrition education curricula and public policy programs. Results can be applied within scale-up nutrition and behavioral education interventions that support parents during infant feeding.

Nutrient intakes and sources of fiber among children with low and high dietary fiber intake: the 2016 feeding infants and toddlers study (FITS), a cross-sectional survey.

BACKGROUND: Increasing dietary fiber intake in children may improve overall diet quality. The purpose of this study was to compare nutrient intakes and sources of fiber between young children with low and high fiber intakes utilizing data from the Feeding Infants and Toddlers Study (FITS) 2016. METHODS: The FITS 2016 was a nationwide, cross sectional survey of caregivers designed to assess food and nutrient intakes, feeding behaviors, and dietary patterns among infants and young children living in the U.S. Energy adjusted macro and micronutrient intakes (nutrients/1000 kcals) of children with energy adjusted fiber intakes (g/1000 kcals) in the highest quartile were compared to those in the lowest quartile with paired t-tests. Sources of fiber for each quartile were ranked according to percent of total fiber intake. RESULTS: Children with fiber intakes in the highest quartile had significantly lower intakes of total fat (mean difference ranged from 7.4-9.6 g, p < 0.0005) and saturated fat (mean difference ranged from 4 to 5.8 g, p < 0.0005), and significantly higher intakes of vitamin B-6 (mean difference ranged from 0.3-0.4 mg, p < 0.0005), magnesium (mean difference ranged from 57.2-61.8 mg, p < 0.0005), iron (mean difference ranged from 2.2-3.7 mg, p < 0.0005), and potassium (mean difference ranged from 318.2 mg to 446.1 mg, p < 0.0005) compared to children in the lowest quartile across all age groups. Children in the highest quartile had higher intakes of nut butters, legumes, fruits, and vegetables and consumed a greater percentage of grains as whole grains than those in the lowest quartile. CONCLUSION: Encouraging intake of fruits, vegetables, legumes, nut butters, and at least 75% of grains as whole grains may help young children improve dietary fiber intake and overall diet quality.

2'-Fucosyllactose Is Well Tolerated in a 100% Whey, Partially Hydrolyzed Infant Formula With Bifidobacterium lactis: A Randomized Controlled Trial.

Human milk oligosaccharides are important components of breast milk. We evaluated feeding tolerance of the human milk oligosaccharide 2'-fucosyllactose (2'FL) in a 100% whey, partially hydrolyzed infant formula with the probiotic Bifidobacterium animalis ssp lactis strain Bb12 (B lactis; Test) as compared with the same formula without 2'FL (Control) in a randomized controlled trial of healthy infants enrolled at 2 weeks of age (±5 days). After 6 weeks of feeding the assigned formula, the primary outcome of tolerance was assessed using the Infant Gastrointestinal Symptom Questionnaire. Stooling, vomiting, spit-up, crying, and fussing were compared between groups. Seventy-nine infants were enrolled and 63 completed the study per protocol (30 Test, 33 Control). Infant Gastrointestinal Symptom Questionnaire scores were similar between groups (Test 20.9 ± 4.8, Control 20.7 ± 4.3, P = .82). Partially hydrolyzed infant formula with 2'FL and B lactis is tolerated well, as confirmed by a validated multi-symptom index.

A Pooled Analysis of Growth and Tolerance of Infants Exclusively Fed Partially Hydrolyzed Whey or Intact Protein-Based Infant Formulas.

BACKGROUND: For infants who are partially or exclusively fed infant formula, many options exist with compositional differences between formulas making choices difficult for caregivers and healthcare professionals. The protein in routine infant formulas differs by the source, fraction of cow's milk protein used, and degree of hydrolysis. All commercially available regulated infant formulas support growth and development, but different stool patterns have been observed based on formula composition. A pooled analysis of seven clinical trials was conducted to examine growth, stool consistency, and stool frequency of infants fed an intact cow's milk-based formula (CMF) or a partially hydrolyzed whey formula (PHF-W) from a single manufacturer. Methods. Individual subject data from seven infant formula growth studies (3 CMF, 4 PHF-W) were pooled and analyzed. All studies included healthy, full-term, formula-fed infants enrolled at 14 days of age with outcomes assessed over 4 months. Gains in weight and length to 4 months were analyzed using linear regression accounting for clustering within study. Outcomes of caregiver-reported stool consistency and frequency were analyzed using a longitudinal multinomial model. RESULTS: Data from 511 infants were included (197 CMF, 314 PHF-W). There were no differences in weight gain between groups. There was no difference in length gain in girls fed PHF-W while boys fed PHF-W had a significant difference of +0.016 cm/month compared to boys fed CMF. Infants fed PHF-W had a significantly higher probability of soft and lower probability of hard stools as compared to infants fed CMF at each time point (p<0.001). Stool frequency was similar between groups. CONCLUSIONS: Infants fed CMF and PHF-W exhibit appropriate growth with comparable gains in weight and length through 4 months. More soft and fewer hard stools are observed in infants fed PHF-W compared to CMF. This difference could help to inform decision-making when choosing an infant formula.

Food Consumption Patterns of Infants and Toddlers: Findings from the Feeding Infants and Toddlers Study (FITS) 2016.

Background: The prevalence of obesity and type 2 diabetes continues to increase. These conditions disproportionately affect minorities and are associated with poor nutrition early in life. Current food-consumption patterns can inform pending dietary guidelines for infants and toddlers. Objective: The aim of this study was to describe infant feeding, complementary feeding, and food and beverage consumption patterns of 0- to 23.9-mo-olds in the general population. Methods: The Feeding Infants and Toddlers Study 2016 is a cross-sectional survey of caregivers of children aged <4 y. Dietary data were collected from a national random sample by using a 24-h dietary recall (n = 3235). The percentage of children consuming foods from >400 food groups was calculated. Differences in the percentage consuming between Hispanic, non-Hispanic white, and non-Hispanic black children aged 0-23.9 mo were evaluated with the use of ORs and 95% CIs. Results: Eighty-three percent of 0- to 23.9-mo-olds (n = 2635) were ever breastfed, 34% of 0- to 3.9-mo-olds (n = 305) and 15% of 4- to 5.9-mo-olds (n = 295) were exclusively breastfed, and 24% of 12- to 14.9-mo-olds (n = 412) consumed breast milk on the day of the recall. Complementary foods were more likely to be introduced before 4 mo in formula-fed infants (27%) than in infants who did not consume formula (5%). Half of 4- to 5.9-mo-olds consumed iron-fortified infant cereal, but few consumed iron-rich meats. Among toddlers (12-23.9 mo; n = 1133), >20% consumed no servings of fruit or vegetables on the day of the recall, approximately half consumed 100% fruit juice, and one-quarter to one-third consumed a sugar-sweetened beverage (SSB). Conclusions: Breastfeeding initiation and duration have improved, but exclusivity remains low. Low consumption of iron-rich foods, fruit, and vegetables and lack of variety in vegetable consumption are problems. Efforts to reduce the consumption of SSBs and 100% fruit juice are warranted in early childhood.

Starch Consumption Patterns in Infants and Young Children.

BACKGROUND: The introduction of starch into an infant's diet is an important milestone in the feeding journey. Intestinal maturity and the presence of digestive enzymes are necessary for the physiologic breakdown of starch and other complementary foods. However, little is known about the consumption patterns of starch containing foods during complementary feeding. METHOD: The 2008 Feeding Infants and Toddlers Study (FITS) is a cross-sectional 24-hour dietary intake survey of a nationally representative sample of infants, toddlers, and preschoolers from birth to 48 months of age. We looked at the age-based prevalence of consumption of starch-containing foods during complementary feeding. RESULTS: We found that about 90% of infants were consuming starch by 6 and 8.9 months, with less than half of infants being exposed to complementary foods from multiple food groups under 6 months. The most common food source of starch was iron-fortified infant cereals, followed by vegetables and fruits. Rice and oats were the most prevalent cereal types, while sweet potatoes, peas and squash were the most commonly consumed starch-containing vegetables. Bananas were the leading starch-containing fruit that was consumed. Around 9 and 11 months, the prevalence of iron-fortified cereals declined and were replaced with lower iron-containing ready-to-eat cereals. There was also a drop in the prevalence of fruit and vegetable consumption once the infant became a toddler. Most bread products consumed by toddlers were not whole grain, but their cereal choices were often whole grain. Other sources of starch were mixed dishes, which contained grains like bread or pasta combined with other types of foods. CONCLUSIONS: Starch enters the infant's diet around the time of complementary feeding, though earlier exposure may occur from certain carbohydrate components of infant formula. Most infants are exposed to starch from grains, followed by vegetables and fruits.

Importance of Dietary Sources of Iron in Infants and Toddlers: Lessons from the FITS Study.

Iron deficiency (ID) affects 13.5% of 1-2 years old children in the US and may have a negative impact on neurodevelopment and behavior. Iron-fortified infant cereal is the primary non-heme iron source among infants aged 6-11.9 months. The objective of this study was to compare iron intakes of infant cereal users with non-users. Data from the Feeding Infants and Toddlers Study 2008 were used for this analysis. Based on a 24-h recall, children between the ages of 4-17.9 months were classified as 'cereal users' if they consumed any amount or type of infant cereal and 'non-users' if they did not. Infant cereal was the top source of dietary iron among infants aged 6-11.9 months. The majority of infants (74.6%) aged 6-8.9 months consumed infant cereal, but this declined to 51.5% between 9-11.9 months and 14.8% among 12-17.9 months old toddlers. Infant cereal users consumed significantly more iron than non-users across all age groups. Infants and toddlers who consume infant cereal have higher iron intakes compared to non-users. Given the high prevalence of ID, the appropriate use of infant cereals in a balanced diet should be encouraged to reduce the incidence of ID and ID anemia.

The Prevalence of Food Allergies in Children Referred to a Multidisciplinary Feeding Program.

OBJECTIVE: To assess the prevalence of food allergy in children presenting to a multidisciplinary feeding program. METHODS: A retrospective chart review was conducted from 302 patients. We recorded history of food reaction, family history of any atopic disease, radioallergosorbent testing, prematurity, birth weight, breastfeeding history, Z-scores, age, and gastrointestinal mucosal biopsy reports with eosinophilic infiltrate. Three categories of possible food allergy were stratified based on increasing evidence of allergy. RESULTS: Possible food allergy was found for 18% (n = 54), likely food allergy for 6% (n = 18), and very likely food allergy for 16% (n = 47) for a total of 40% classified in a food allergy group. Having been breastfed correlated with likelihood of food allergy but tube-feeding dependence did not. CONCLUSION: This study revealed a higher proportion of children in a feeding program with food allergy compared to the general population, but larger prospective studies are needed to confirm the association.

Clinical Presentation and Five-Year Therapeutic Management of Very Early-Onset Inflammatory Bowel Disease in a Large North American Cohort.

OBJECTIVE: To evaluate the presentation, therapeutic management, and long-term outcome of children with very early-onset (VEO) (≤ 5 years of age) inflammatory bowel disease (IBD). STUDY DESIGN: Data were obtained from an inception cohort of 1928 children with IBD enrolled in a prospective observational registry at multiple centers in North America. RESULTS: One hundred twelve children were ≤ 5 years of age with no child enrolled at <1 year of age. Of those, 42.9% had Crohn's disease (CD), 46.4% ulcerative colitis (UC), and 10.7% had IBD-unclassified. Among the children with CD, children 1-5 years of age had more isolated colonic disease (39.6%) compared with 6- to 10-year-olds (25.3%, P = .04), and 11- to 16-year-olds (22.3%, P < .01). The change from a presenting colon-only phenotype to ileocolonic began at 6-10 years. Children 1-5 years of age with CD had milder disease activity (45.8%) at diagnosis compared with the oldest group (28%, P = .01). Five years postdiagnosis, there was no difference in disease activity among the 3 groups. However, compared with the oldest group, a greater proportion of 1- to 5-year-olds with CD were receiving corticosteroids (P < .01) and methotrexate (P < .01), and a greater proportion of 1- to 5-year-olds with UC were receiving mesalamine (P < .0001) and thiopurine immunomodulators (P < .0002). CONCLUSIONS: Children with VEO-CD are more likely to have mild disease at diagnosis and present with a colonic phenotype with change to an ileocolonic phenotype noted at 6-10 years of age. Five years after diagnosis, children with VEO-CD and VEO-UC are more likely to have been administered corticosteroids and immunomodulators despite similar disease activity in all age groups. This may suggest development of a more aggressive disease phenotype over time.

Retrospective cohort study of methotrexate use in the treatment of pediatric Crohn's disease.

BACKGROUND: Methotrexate (MTX) use as an alternative to thiopurines in the treatment of Crohn's disease (CD) in children is increasing. This study was undertaken to assess safety and efficacy of MTX in children with CD. METHODS: Patients treated with MTX with a minimum of 1-year follow-up were identified in the Pediatric IBD Collaborative Research Group Registry, a prospective inception cohort study started in 2002. The clinical efficacy and safety of MTX were analyzed retrospectively. RESULTS: Two hundred ninety patients treated with MTX were identified. One hundred seventy-two patients received at least 3 months of MTX without thiopurine or biologicals and had ≥1 year of follow-up. Eighty-one of 172 patients (47%) received MTX as first immunomodulator (IMM), of which 22 (27%) achieved ≥12 months of sustained clinical remission without surgery, thiopurine, biologicals, or corticosteroids. Those receiving MTX as second IMM achieved similar remission rate (35%, P = not significant). Fourteen percent received MTX as first IMM in 2002 and 60% in 2010 (P = 0.005). Disease location did not affect outcomes. MTX doses were equivalent in both groups. Fifteen percent of patients developed an alanine aminotransferase >60 international units/liter and 12% developed a white blood cell <4000 cells per microliter while on MTX. Only 4% of these discontinued MTX completely. A small group of 6 centers, which contributed only about one-third of patients with CD in the registry, contributed nearly two-thirds of the patients receiving MTX (P < 0.001). CONCLUSIONS: MTX use as first choice IMM is increasing in pediatric CD. MTX provided sustained clinical remission in nearly one-third of patients with minimal toxicity. There is large center-to-center variability in its use.

Liver enzyme elevations within 3 months of diagnosis of inflammatory bowel disease and likelihood of liver disease.

BACKGROUND: Inflammatory bowel disease-associated liver diseases (IBD-LDs) include autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and an overlap syndrome. Prospective unbiased multicenter data regarding the frequency of IBD-LD in patients with pediatric inflammatory bowel disease (IBD) are lacking. We examined early alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) elevations in children diagnosed as having IBD and assessed the likelihood of IBD-LD. METHODS: Data collected from the prospective observational Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry enrolling children of age <16 years within 30 days of diagnosis. AIH, PSC, and overlap syndrome were diagnosed using local institutional criteria. RESULTS: A total of 1569 subjects had liver enzymes available. Of the total, 757 had both ALT and GGT, 800 had ALT only (no GGT), and 12 had GGT only (no ALT). Overall, 29 of 1569 patients (1.8%) had IBD-LD. IBD-LD was diagnosed in 1 of 661 (0.15%) of patients with both ALT and GGT ≤ 50 IU/L compared with 21 of 42 (50%) of patients with both ALT and GGT > 50 (odds ratio 660, P < 0.0001). Of the 29 patients with IBD-LD, 21 had PSC, 2 had AIH, and 6 had overlap syndrome. IBD-LD was more common in patients with ulcerative colitis and IBD-unclassified (indeterminate colitis) than in those with Crohn disease (4% vs 0.8%, respectively, P < 0.001). CONCLUSIONS: Elevation of both ALT and GGT within 90 days after the diagnosis of IBD is associated with a markedly increased likelihood of IBD-LD. Both ALT and GGT levels should be measured in all of the pediatric patients newly diagnosed as having IBD.

Diffuse intestinal ganglioneuromatosis in a child.

A 7 year old male with a history of congenital neutropenia and growth hormone deficiency presented with abdominal pain, fevers, and diarrhea. Imaging and endoscopy revealed significant inflammation of the ascending colon with stenosis at the level of the hepatic flexure. A right hemicolectomy was performed, and pathologic findings were consistent with diffuse intestinal ganglioneuromatosis. Due to recurrent mass effect at the intestinal anastomotic site detected radiologically, a second intestinal resection was performed 7 months later. Genetic testing was negative for mutations in the RET protooncogene, NF1 and PTEN tumor suppressor genes. We report a case of diffuse intestinal ganglioneuromatosis in a child with congenital neutropenia.

Outcome following aminosalicylate therapy in children newly diagnosed as having ulcerative colitis.

OBJECTIVES: Despite a paucity of published supporting data, 5-aminosalicylate (5-ASA) use in pediatric ulcerative colitis (UC) is common. The present study describes the use and outcome of a large multicenter inception cohort of children with UC treated with 5-ASA. METHODS: Data were obtained from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, a prospective North American observational study of children newly diagnosed as having inflammatory bowel disease ages 16 years or younger. Patient data are recorded at diagnosis, 30 days, and then quarterly. Patients are managed by physician dictate, not protocol. Disease activity is classified by physician global assessment. The primary outcome examined was corticosteroid (CS) free, inactive UC at 1 year following initiation of 5-ASA within 30 days of diagnosis (with or without concomitant CS use) without the need for rescue therapy (immunomodulators, biologics, or colectomy). RESULTS: Study subjects included 213 patients newly diagnosed as having UC who received oral 5-ASA compounds (115 of whom also received CS) during the first 30 days after diagnosis, and no other oral therapies for the treatment of UC. Of these 213 patients, 86 (40%) were CS free and physician global assessment inactive at 1 year without rescue. Outcome was not associated with disease severity at diagnosis, demographic or laboratory factors examined, or initial dose of 5-ASA used. CONCLUSIONS: Forty percent of children taking 5-ASA as primary maintenance therapy at diagnosis are in CS-free remission after 1 year of treatment. Further pediatric studies will be needed to address whether increased adherence and/or higher dosing schedules will improve outcomes.

Budesonide use in pediatric Crohn disease.

BACKGROUND AND AIM: Budesonide (BUD) is being used in pediatric Crohn disease (CD) because it is believed to have the potential to reduce corticosteroid-related toxicity; however, few data are available describing its use. The aim of the present study was to describe BUD use in an inception cohort of pediatric patients with CD. METHODS: Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. Use of BUD in children with CD was examined. RESULTS: BUD was used in 119 of 932 (13%) of children with newly diagnosed CD, with 56 of 119 (47%) starting BUD ≤ 30 days of diagnosis (26/56 with ileum and/or ascending colon [IAC] disease). BUD was used as monotherapy (9%), in combination with 5-aminosalicylates (77%), or in combination with immunomodulators (43%). Forty-three percent (24/56) went on to receive conventional corticosteroid at some point following their first BUD course. For the 63 of 119 (53%) who started BUD beyond the diagnosis period, 51 of 63 (81%) also received prednisone, with BUD used as a means of weaning from prednisone in 17 of 63 (27%). Patients with IAC disease who received BUD ≤ 30 days of diagnosis were just as likely to have received conventional corticosteroids by 1 year as were those who did not receive BUD ≤ 30 days of diagnosis. Two-thirds (77/119) of patients received BUD for ≤ 6 months. CONCLUSIONS: BUD is being used among pediatric patients newly diagnosed as having CD, although the majority does not have disease limited to the IAC. BUD monotherapy was rare, and further data are required to better define the role of BUD in the treatment of pediatric CD.

Presentation and outcome of histoplasmosis in pediatric inflammatory bowel disease patients treated with antitumor necrosis factor alpha therapy: a case series.

BACKGROUND: Antitumor necrosis factor alpha (aTNF) therapies are commonly used in the treatment of pediatric inflammatory bowel disease (IBD). However, inhibition of the TNF-alpha pathway predisposes to serious infections, including histoplasmosis, which is the most common invasive fungal infection in individuals on aTNF therapy and carries a high mortality rate when associated with delayed diagnosis. Few data exist on the frequency, presentation, and appropriate treatment of pediatric patients with histoplasmosis on aTNF therapy. METHODS: Following Institutional Review Board approval, cases were identified then reviewed with their primary gastroenterologist and infectious disease specialists. RESULTS: Herein we describe histoplasmosis in five pediatric patients receiving aTNF therapy for IBD in an endemic area. CONCLUSIONS: Histoplasmosis is an important complication of treatment with TNF-alpha neutralizing agents. Children with IBD treated with aTNF therapy who develop the infection may present with minimal pulmonary symptoms. While discontinuation of aTNF therapy is important initially, few data exist to determine when and how aTNF therapy can be reinstituted. Recognition of Histoplasma capsulatum is often delayed due to the overlap of symptoms with some of the extraintestinal manifestations of IBD and other more prevalent infectious complications.

Factors that determine risk for surgery in pediatric patients with Crohn's disease.

BACKGROUND & AIMS: We examined the incidence of Crohn's disease (CD)-related surgery in a multi-center, inception cohort of pediatric patients with CD. We also examined the effect of starting immunomodulator therapy within 30 days of diagnosis. METHODS: Data from 854 children with CD from the Pediatric Inflammatory Bowel Disease Collaborative Research Group who were diagnosed with CD between 2002 and 2008 were analyzed. RESULTS: Overall, 76 (9%) underwent a first CD-related surgery, 57 (7%) underwent a first bowel surgery (bowel resection, ostomy, strictureplasty, or appendectomy), and 19 (2%) underwent a first non-bowel surgery (abscess drainage or fistulotomy). The cumulative risks for bowel surgery, non-bowel surgery, and all CD-related surgeries were 3.4%, 1.4%, and 4.8%, respectively, at 1 year after diagnosis and 13.8%, 4.5%, and 17.7%, respectively, at 5 years after diagnosis. Older age at diagnosis, greater disease severity, and stricturing or penetrating disease increased the risk of bowel surgery. Disease between the transverse colon and rectum decreased the risk. Initiation of immunomodulator therapy within 30 days of diagnosis, sex, race, and family history of inflammatory bowel disease did not influence the risk of bowel surgery. CONCLUSIONS: In an analysis of pediatric patients with CD, the 5-year cumulative risk of bowel surgery was lower than that reported in recent studies of adult and pediatric patients but similar to that of a recent retrospective pediatric study. Initiation of immunomodulator therapy at diagnosis did not alter the risk of surgery within 5 years of diagnosis.

Extraintestinal manifestations of pediatric inflammatory bowel disease and their relation to disease type and severity.

OBJECTIVES: Although it is known that extraintestinal manifestations (EIMs) commonly occur in pediatric inflammatory bowel disease (IBD), little research has examined rates of EIMs and their relation to other disease-related factors in this population. The purpose of this study was to determine the rates of EIMs in pediatric IBD and examine correlations with age, sex, diagnosis, disease severity, and distribution. PATIENTS AND METHODS: Data were prospectively collected as part of the Pediatric IBD Collaborative Research Group Registry, an observational database enrolling newly diagnosed IBD patients <16 years old since 2002. Rates of EIM (occurring anytime during the period of enrollment) and the aforementioned variables (at baseline) were examined. Patients with indeterminate colitis were excluded from the analysis given the relatively small number of patients. RESULTS: One thousand nine patients were enrolled (mean age 11.6 +/- 3.1 years, 57.5% boys, mean follow-up 26.2 +/- 18.2 months). Two hundred eighty-five (28.2%) patients experienced 1 or more EIMs. Eighty-seven percent of EIM occurred within the first year. Increased disease severity at baseline (mild vs moderate/severe) was associated with the occurrence of any EIM (P < 0.001), arthralgia (P = 0.024), aphthous stomatitis (P = 0.001), and erythema nodosum (P = 0.009) for both Crohn disease (CD) and ulcerative colitis (UC) during the period of follow-up. Statistically significant differences in the rates of EIMs between CD and UC were seen for aphthous stomatitis, erythema nodosum, and sclerosing cholangitis. CONCLUSIONS: EIMs as defined in this study occur in approximately one quarter of pediatric patients with IBD. Disease type and disease severity were commonly associated with the occurrence of EIMs.