Acute pancreatitis in children with inflammatory bowel disease: Risk factors, clinical course, and prognosis.

OBJECTIVES: To characterize the clinical course of acute pancreatitis (AP) in pediatric inflammatory bowel disease (IBD) patients compared to children with AP without IBD and to identify risk factors associated with AP among IBD patients. METHODS: This retrospective, single-center study compared clinical characteristics of children (<19 years) with AP with and without concomitant IBD who were hospitalized 2005-2019. We also conducted a risk factor analysis of AP development in pediatric IBD. RESULTS: Sixty-eight (54% males) patients with 120 episodes of AP were admitted at a median age of 15.3 years. Thirteen patients (14 episodes) had a co-diagnosis of IBD, representing 4% of our IBD patient population. The AP-IBD patients presented with lower amylase levels compared to the non-IBD patients (160 [interquartile range, IQR: 83-231] vs. 418 [IQR: 176-874] U/L, p > 0.01), all had a mild pancreatitis, and none required invasive intervention. The presumed etiology for AP in all IBD patients was IBD-related: IBD flare-up in five, side effects of medications in two, and undetermined in seven. The only risk factor for AP development among IBD patients was IBD-associated arthritis (23% vs. 3% for IBD-non-AP, p = 0.04), while extracolonic Crohn's disease and induction therapy with nutrition were negative risk factors (15% vs. 51%, p = 0.05, and 8% vs. 44%, p = 0.04, respectively). Other parameters, including disease type and medications, were nonsignificant. CONCLUSION: The clinical course of AP in pediatric IBD patients is mild. Only IBD-associated arthritis emerged as a risk factor for the development of AP, while, unexpectedly, IBD medication did not.

Pediatric feeding disorders among children with parental history of feeding disorders: a distinct group of patients with unique characteristics.

To investigate factors associated with pediatric feeding disorders (PFD) among children of parents that reported to have had feeding disorders during their own childhood compared to children with PFD with no history of parental PFD. We retrospectively reviewed the medical records of children diagnosed with PFD according to the recent WHO-based definition. The demographic and clinical characteristics of children with PFD with a parental history of PFD were compared to those of children with a PFD with no history of parental PFD. Included were 231 children with PFD (median [interquartile range] age 10 months [5.5-29] at diagnosis, 58% boys) of whom 133 children had parents without PFD and 98 children had parents with PFD. Unexpectedly, children of parents without PFD had a higher rate of low birth weight (28% vs. 19%, respectively, p = 0.007), more delivery complications (10% vs. 2%, p = 0.006), more hospitalizations (33% vs. 17%, p = 0.004), more prescription medications (27% vs. 18%, p = 0.05), and a higher percent of gastrostomy tube use (6% vs. 0, p = 0.02). Moreover, more parents with PFD had academic background compared with parents without PFD (72% vs. 59%, p = 0.05). There were no significant group differences in sex, history of breastfeeding, parental marital status, or type of the child's feeding disorder.  Conclusion: PFD among children with a parental history of PFD comprise a distinct group of patients with unique characteristics and outcomes. Since parental feeding history may explain their child's PFD in highly differing ways, such information may help in devising a specific family-based and multidisciplinary treatment plan for those children. What is Known: • Pediatric feeding disorder (PFD) is relatively common and its prevalence is increasing. • Information on an association between parental PFD and their child's feeding disorder is limited. What is New: • PFD among children with a parental history of PFD comprise a distinct group of patients with various characteristics and outcomes. • The parents' feeding history during childhood may provide important clues to their child's PFD.

BMI in the lower and upper quartiles at diagnosis and at 1-year follow-up is significantly associated with higher risk of disease exacerbation in pediatric inflammatory bowel disease.

Inflammatory bowel disease (IBD) has been associated with underweight and malnutrition, but obesity may also serve as a negative prognostic factor. This study aimed to present the longitudinal course of height, weight, and body mass index (BMI) of children from IBD diagnosis to 18 months of follow-up, and to describe the impact of BMI on the clinical course of the disease. One hundred and fifty-two children were identified, of whom 85 had Crohn's disease (CD) and 67 had ulcerative colitis (UC). During a median (interquartile range) follow-up of 2.95 (1.73-4.5) years, weight and BMI Z-scores increased in the first 18 months since diagnosis in both the CD (P < 0.001) and UC (P < 0.028) groups. BMI in lower and upper quartiles at diagnosis was associated with higher risk of hospitalization (hazard ratio [HR] = 2.72, P = 0.021). In a multivariate analysis, BMI in the lower quartile at diagnosis and at 6, 12, and 18 months was associated with higher risk of disease exacerbation (HR = 2.36, 1.90, 1.98, and 2.43, respectively, P < 0.021), as was BMI in the upper quartile (HR = 2.59, 2.91, and 2.29, respectively, P < 0.013).Conclusion: BMI in the lower and upper quartiles at diagnosis and during follow-up was associated with a more severe disease course in children with IBD. What is Known: • Inflammatory bowel disease (IBD) has been associated with underweight and malnutrition. • The impacts of weight and body mass index (BMI) on the presentation and course of IBD have been mainly investigated in the adult population. What is New: • In the era of the obesity epidemic, this study identifies both low and high BMIs at diagnosis and at follow-up as a marker for poor outcome in pediatric IBD. • The results support using BMI as a predictor of IBD course and prognosis.

Age and pain score before gastrointestinal endoscopies in children are predictors for post procedure pain.

BACKGROUND: Gastrointestinal endoscopy may be associated with pain and anxiety. Predictors for high pain scores after endoscopies in children are not known. The aim of our study was to identify risk factors for prolonged recovery and higher pain scores after gastrointestinal endoscopy in children. METHODS: All the children that were electively admitted for gastrointestinal endoscopies were included. We retrospectively collected demographic, clinical and endoscopic data as well as information on the recovery process. A numerical rating scale and the Faces, Legs, Activity, Cry, and Consolability Scale were used for pain scoring. RESULTS: During the study period (01/2016-10/2016), 284 children (median age 10.7 years, interquartile range 6.7-14.8) were recruited. In a univariate analysis, older age, higher pre-procedure pain scores, longer procedure durations, higher number of biopsies and longer recovery duration were associated with higher post-procedure pain scores. In a multivariate analysis higher pain scores before the procedure (OR 12.42, 95% CI 3.67-42, P < 0.001) and older age (OR 1.016, 95% CI 1.007-1.025, P < 0.001) were associated with higher pain scores after the procedure. Children with a higher pain score before the procedure also had a longer recovery period (OR 5.28, 95% CI (1.93-14.49), P = 0.001). CONCLUSION: Older age and higher pain score before the procedure were identified as predictors for higher pain score after pediatric gastrointestinal endoscopies. Children with these risk factors should be identified before the procedure in order to personalize their post-procedure management.

Predictors for Complicated Disease Course after Stepping Down from Combination to Antitumor Necrosis Factor Alpha Monotherapy in Children with Inflammatory Bowel Disease.

OBJECTIVE: Combinations of antitumor necrosis factor alpha (TNFα) and immunomodulators may be indicated in high-risk inflammatory bowel disease patients. Our aims were to compare disease course between children that did and did not step down to anti-TNFα monotherapy and to define risk factors for complicated disease course after stepping down. METHODS: A retrospective review of the medical records of consecutive children who were treated with combination therapy. RESULTS: Of 64 children, 32 continued combination therapy while the others stepped down to monotherapy (median duration of 6 months [range 6-10]). Children that stepped down had a trend of lower anti-TNFα levels (median [interquartile range] of 2.4 [1-4.2] µg/mL) compared to those that did not step down (4.5 [2.2-6.23] µg/mL, p = 0.065). Children with Crohn's disease that stepped down had a significantly higher risk for disease exacerbation, hospital admission, and operation (p < 0.025). Univariate analysis revealed that penetrating phenotype, upper gastrointestinal involvement, higher disease activity at diagnosis, and lower anti-TNFα levels under combination therapy were predictors for complicated course after stepping down. CONCLUSION: Stepping down to anti-TNFα monotherapy may be related to lower anti-TNFα levels and to a more complicated disease course thereafter. Predictors for a complicated course were identified.

Higher prevalence of obesity among children with functional abdominal pain disorders.

BACKGROUND: Functional abdominal pain (FAP) disorders are one of the most common gastrointestinal disorders in children. We aimed to define the association between obesity and functional abdominal pain (FAP) disorders and to assess differences between overweight/obese children and normal weight children with FAP disorders. METHODS: We conducted a retrospective study of children (2-18 years old) with a clinical diagnosis of FAP who were followed-up in our pediatric gastroenterology unit between 1/2016-10/2018. FAP disorders were defined according to the ROME IV criteria. Body mass index (BMI) percentiles were defined by CDC standards. Patients with BMIs ≥85th percentile were designated as being overweight/obese. A population control group was obtained from the 2015-2016 Israel national health survey. RESULTS: Data from 173 children with FAP disorders (median age 11.5 years, 114 females) were included. Seventy-one children (41%) were classified as having functional abdominal pain-NOS, 67 (38.7%) as having irritable bowel syndrome (IBS), and 35 (20.2%) has having functional dyspepsia. Fifty-three children (30.6%) were classified as being overweight/obese. Adolescents with FAP disorders had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30%, respectively, p = 0.04). Children with FAP and overweight were older [12.4 (range 9.8-15.3) vs. 10.8 (7.4-14.1) years, p = 0.04] and had more hospitalizations due to FAP (20.8% vs. 7.6%, p = 0.01) compared to Children with FAP and normal weight. CONCLUSIONS: Adolescents with FAP had higher prevalence of overweight/obesity compared to controls. Future studies are warranted to raise awareness of weight issues in FAP and determine the effect of weight loss on FAP.

Young Age Predicts Acute Pancreatitis Severity in Children.

OBJECTIVES: The course and evolution of pediatric acute pancreatitis (AP) is poorly understood. Prognostication models in children perform poorly and lack consensus. We aimed to identify predictors of AP severity, and the risk for AP recurrence. METHODS: We retrospectively studied all patients hospitalized with AP at a single tertiary center, between January 1995 and June 2016. Patient demographics and admission laboratory data were assessed for severity and recurrence prediction. RESULTS: A total of 68 patients accounting for a total of 117 (15 moderate-severe) AP episodes were reviewed. Patients with moderate-severe disease were significantly younger (median [interquartile range (IQR)] of 8.3 [4.0-14.4] vs 13.8 [8.1-16.0] years, P = 0.02). Young age at presentation was associated with odds ratio of 3.8 (confidence interval [CI] 1.2-12.1) for children younger than 12 years and 5.8 (CI 1.6-21.4) for children younger than 6 years for developing moderate-severe disease.Further subanalysis of the 59 patients with first-time AP episodes, demonstrated younger age (median [IQR] of 5.3 [2.9-10.4] vs 12.0 [6.3-15.8] years, P = 0.03) and elevated white blood cell count (median [IQR] of 22.8 [11.8-31.3] vs 11.0 [8.1-14.6] 10/L, P < 0.01) of patients with moderate-severe disease, conferring a risk for moderate-severe disease with odds ratio of 7.5 (CI 1.5-38.2) for children younger than 6 years and 5.3 (CI 1.1-25.4) for patients with white blood cell count >15 × 10/L, respectively. Fourteen (23.7%) of 59 patients with first-time episodes had recurrent AP. Analysis of the data at the primary episode failed to identify predictors to indicate future recurrence. CONCLUSIONS: In our cohort, only young age (<12 years) predicted AP severity. No parameters were identified to predict future development of AP recurrence.

Ultra-short Celiac Disease Is a Distinct and Milder Phenotype of the Disease in Children.

BACKGROUND AND AIMS: Approximately 10% of children with celiac disease (CD) have ultra-short celiac disease (USCD), where histological abnormalities are limited to the duodenal bulb. The aim of our retrospective study was to identify clinical and serological characteristics at baseline and at follow-up of children with USCD. METHODS: All children that were diagnosed with CD in our unit during 7/2010-12/2017, in whom biopsies were taken from duodenal bulb and second part, were included. We compared disease characteristics and course between children with USCD and children with involvement in the second part of the duodenum. RESULTS: Out of 3740 children who underwent upper gastrointestinal endoscopies, 648 were diagnosed with CD. Seventy-one (11%) of those children had limited involvement in the duodenal bulb. The USCD group included more females (P = 0.021), were older (P = 0.005), had a lower prevalence of diarrhea (P = 0.003), anemia (P = 0.007), anti-tissue transglutaminase (TTG) antibodies count (P < 0.001) at presentation, lower frequency of endoscopic abnormality, lower Marsh score, and a trend toward shorter time to the normalization of anti-TTG antibodies under a gluten-free diet compared to the extensive CD. There were no differences in body mass index or duration of symptoms before diagnosis. CONCLUSION: Children with USCD presented with a distinct phenotype of milder symptoms, lower celiac serology, and milder endoscopic and histological findings, with a trend toward faster normalization under a gluten-free diet compared to those with extensive CD. Further studies are needed to determine the long-term course and prognosis of USCD.

High and low body mass index may predict severe disease course in children with inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD) has been historically associated with underweight and malnutrition. The impact of both underweight and obesity on the clinical course of IBD in adults is controversial. This study described the association between body mass index (BMI) at diagnosis to disease course in children with IBD. METHODS: We reviewed the medical records of children with IBD from the database of the 'Dana-Dwek' Children's Hospital between 2010 and 2016. Demographic and anthropometric data were collected as were disease characteristics, course and therapy. Patients were categorized in quartiles according to BMI percentiles at diagnosis (Q1-Q4). RESULTS: Of 100 children who were identified, 62 had Crohn's disease (CD) and 38 had ulcerative colitis (UC). The median age (interquartile range, IQR) at diagnosis was 13.7 (range 11.9-15.2) years. The median (IQR) follow-up was 2.1 (1.2-3.8) years. At diagnosis, 46 children (46%) were in Q1, 20 (20%) in Q2, 19 (19%) in Q3 and 15 (15%) in Q4. Prolonged time to diagnosis was associated with BMI in Q1 and Q4, as well as high disease activity at diagnosis (p < .001). In a multivariate analysis, BMI in the lower and upper quartiles was associated with disease exacerbation (HR 3.212 and 4.651, respectively, p = .016) and anti-tumor necrosis factor (TNF) therapy (HR 4.489 and 3.972, respectively, p = .021). CONCLUSIONS: BMI in the lower and upper quartiles was associated with more severe disease course in children with IBD. BMI may serve as a simple and highly accessible predictor of pediatric IBD course and prognosis.

One-third of children with lactose intolerance managed to achieve a regular diet at the three-year follow-up point.

AIM: This study described outcomes following treatment for lactose intolerance, which is common in children. METHODS: The medical records of children aged 6-18 years who underwent lactose hydrogen breath testing at Dana-Dwek Children's Hospital, Tel Aviv, Israel, from August 2012 to August 2014 were analysed. We compared 154 children with gastrointestinal symptoms and positive lactose hydrogen breath tests to 49 children with negative test results. RESULTS: Of the 154 children in the study group, 89 (57.8%) were advised to follow a lactose-restricted diet, 32 (20.8%) were advised to avoid lactose completely, 18 (11.7%) were instructed to use substitute enzymes, and 15 (9.7%) did not receive specific recommendations. Only 11 patients (7.1%) received recommendations to add calcium-rich foods or calcium supplements to their diet. Lactose reintroduction was attempted in 119 of 154 patients (77.3%), and 65 of 154 (42.2%) experienced clinical relapses. At the final follow-up of 3.3 years, 62.3% of the study children were still observing a restricted diet. Older children and those who were symptomatic during lactose hydrogen breath testing were more likely to be on a prolonged restricted diet. CONCLUSION: Our long-term follow-up of lactose-intolerant children showed that only a third were able to achieve a regular diet.

The Association Between Iron Deficiency at Diagnosis, Female Sex, and Tissue Transglutaminase Antibody Normalization in Pediatric Celiac Disease.

BACKGROUND: Iron deficiency (ID) is one of the most common manifestations of Celiac disease (CD). We aimed to determine whether ID at CD diagnosis affects tissue transglutaminase antibody (TTG) normalization rate among pediatric CD patients adhering to a gluten-free diet (GFD). METHODS: We conducted a retrospective, observational cohort study that enrolled CD subjects aged 2-18y, diagnosed between Jan 2016 and Dec 2020. Demographic and laboratory data were collected at diagnosis and one year after adherence to GFD. ID was determined according to hemoglobin and ferritin levels. We compared CD subjects with and without ID at CD diagnosis in relation to TTG normalization at one year. RESULTS: Our cohort included 118 pediatric CD subjects. At diagnosis, 61 (51.7%) of CD subjects had ID, of whom 27 (44.3%) were female, compared to 46 (80.7%) females in the non-ID group (p<0.001). Median age at CD diagnosis was 5.7y (IQR 4-8.4, range 2-14) and 7.2y (IQR 4.7-10.8, range 0.9-16), and among those with and without ID, respectively (p=0.1). After one year of adherence to GFD, TTG normalization was achieved in 38 (65.5%) and 28 (53.8%) of those with and without ID at CD diagnosis, respectively (p=0.21). However, TTG normalization was achieved in 38 (79.2%) of males compared to 42 (49.4%) of females (p=0.001). CONCLUSIONS: ID at CD diagnosis was not associated with lower rates of TTG normalization at one year among pediatric patients adhering to GFD. However, TTG normalization at one year was significantly more frequent among male subjects compared to females.

Factors associated with age of presentation of pediatric feeding disorder.

AIM: Understanding the association between pediatric feeding disorder (PFD) and age of presentation is limited. We aimed to investigate factors associated with PFD among different age groups. METHODS: Retrospective analysis of medical records of infants and toddlers diagnosed with PFD, according to the World Health Organization-based definition. We compared children aged 1-12 months to those aged 13-72 months. RESULTS: Included were 253 children with PFD (median [interquartile range] age 16.4 [9.5-33] months at diagnosis, 56% boys). Significantly more children in the younger age group were girls (52.6% vs. 34.4%, respectively, p = .03) and preterm (25% vs. 14%, p = .03). They had more hospitalizations (34% vs. 23%, p = .03) and needed more prescription medications (36% vs. 17%, p < .01). Additionally, disturbances in oral intake were primarily linked to feeding skills dysfunction in the younger group and nutritional dysfunction in the older group (39.6% vs. 23.7% and 55% vs. 38%, respectively, p = .02). CONCLUSIONS: Infants under 1 year old with PFD represent a distinct patient group with unique characteristics and outcomes. The age of presentation plays a significant role in children with PFD, necessitating tailored treatment strategies.

Demographic and clinical parameters are comparable across different types of pediatric feeding disorder.

Knowledge and understanding of risk mechanisms associated with pediatric feeding disorder (PFD) remain limited. We aimed to investigate factors associated with PFD and their relation to specific PFD types according to the recent consensus WHO-based definition. We retrospectively reviewed the medical records of children with PFD and retrieved their demographic and clinical characteristics. Healthy age- and sex-matched children served as controls. Included were 254 children with PFD [median (interquartile range) age 16.4 (9.5-33) months at diagnosis] and 108 children in the control group [median age 24.85 (14.5-28.5) months]. According to the WHO-based definition, disturbances in oral intake were predominantly related to nutritional dysfunction in 118 (46.6%), feeding skill dysfunction in 83 (32.3%), medical conditions in 42 (16.7%) and psychosocial dysfunction in 11 (4.4%). In multivariate analysis, children with PFD had a higher risk for lower socioeconomic background (P < 0.01) and low birth weight (26.8% compared to 7.4%, P < 0.001). Moreover, significantly fewer children in the PFD group were breastfed (75% versus 89%, P = 0.003). There were no significant differences in any of those variables between PFD types. In conclusion, low socioeconomic status, lack of breastfeeding, and low birth weight were significantly more frequent in children with PFD. PDF manifest as multiple dysfunctions, thus highlighting the need to offer these children and their families multidisciplinary care.

Vitamin D Decreases Hepcidin and Inflammatory Markers in Newly Diagnosed Inflammatory Bowel Disease Paediatric Patients: A Prospective Study.

BACKGROUND AND AIMS: The role of hepcidin in inflammatory bowel disease [IBD] in children with anaemia is poorly understood. However, it has been shown that vitamin D suppresses hepcidin expression. We aimed to assess serum hepcidin levels and the effect of vitamin D treatment on those levels in newly diagnosed IBD paediatric patients. METHODS: Eighty-five children were prospectively recruited in the Dana-Dwek Children's Hospital [40 newly diagnosed IBD, 45 healthy controls, 47% female, mean age 13.5 ± 3.4 years]. Blood samples for measurement of interleukin 6 [IL-6], C-reactive protein [CRP], hepcidin, iron parameters and 25-hydroxyvitamin D [25-(OH)-D] levels were obtained at baseline. Patients with mild-to-moderate signs and symptoms of IBD were treated with 4000 units of vitamin D daily for 2 weeks, after which the blood tests were repeated. RESULTS: Basal hepcidin, IL-6, CRP and platelet counts were significantly higher, and haemoglobin, serum iron and transferrin levels were significantly lower in the IBD children compared to controls [p < 0.001]. Eighteen patients completed 2 weeks of treatment with vitamin D. Following treatment, serum 25-(OH)-D concentrations increased by 40% [from 22.5 to 32.5 ng/mL], and serum hepcidin, CRP and ferritin levels decreased by 81%, 81% and 40% [from 33.9 to 6.7 ng/mL, from 23.9 to 4.7 mg/L, and from 27 to 16 ng/mL, respectively] [p ≤ 0.001]. CONCLUSION: Serum hepcidin levels were significantly higher in IBD paediatric patients compared to controls. Following vitamin D treatment, serum hepcidin concentration decreased significantly. These findings suggest a potential role for vitamin D in treating anaemia in IBD children. CLINICALTRIALS.GOV NUMBER: NCT03145896.

Misdiagnosis of Acute Appendicitis in Children Attending the Emergency Department: The Experience of a Large, Tertiary Care Pediatric Hospital.

Background Missed appendicitis is a frequent cause of professional liability for emergency department (ED) physicians. Our objective was to assess and compare the presentations of patients in whom the diagnosis of appendicitis was missed with those in whom it was correctly diagnosed on their first ED visit and to identify the clinical features that characterized the two groups. Methods This study is a retrospective review of all ED children with proven appendicitis between January 2010 and December 2013. Historical, clinical, and laboratory features of patients missed and correctly diagnosed during their first ED visit were compared. The literature on this subject was also reviewed. Results A total of 400 patients were included in this study. Fifteen (3.75%) patients were considered to be misdiagnoses, the most common misdiagnosis being acute gastroenteritis (26.6%). Thirty-three percent of misdiagnosed patients had undergone an ultrasound compared with 87% of correctly diagnosed patients (p < 0.05). Conclusion Our incidence of missed appendicitis compares favorably with the 6.9 to 27.6% incidence reported in the literature. Our relatively low incidence may be a result of medical practice, especially during night shifts, and the availability of ultrasound 24 hours a day.