Gut virome profile in healthy Saudi children.

Background: The role of viruses is well known in health and disease. The aim of this report was to describe the profile of viruses in the gut of healthy Saudi children. Methods: In 20 randomly selected school age children from Riyadh, stool samples were collected in cryovials and stored at -80° C. At the time of analysis, the samples were sent by express mail in a temperature-controlled container to the laboratory in the USA, Viral DNA was isolated and shotgun metagenomic sequencing was performed. The abundance of each organism was expressed as an average relative percentage across the viral phylogenetic tree from phyla to species. Results: The median age of the children was 11.3 (range 6.8-15.4) years, and 35% were males. Caudovirales were the most abundant bacteriophage order (77%) and Siphoviridae, Myoviridae, and Podoviridae families predominated, accounting for 41%, 25%, and 11%, respectively. Among the viral bacteriophage species, the most abundant were the Enterobacteria phages. Conclusion: The profile and abundance of the gut virome in healthy Saudi children reveal important differences from the literature. Further studies from different populations with larger sample sizes are needed to understand the role of gut viruses in the pathogenesis of disease in general and in the response to fecal microbiota therapy in particular.

Bacterial dysbiosis predicts the diagnosis of Crohn's disease in Saudi children.

BACKGROUND: Studies have reached different conclusions regarding the accuracy of dysbiosis in predicting the diagnosis of Crohn's disease (CD). The aim of this report is to assess the utility of mucosal and fecal microbial dysbiosis as predictors in the diagnosis of this condition in Saudi children. METHODS: Tissue and fecal samples were collected prospectively from children with final diagnosis of CD and from controls. Bacterial DNA was extracted and sequenced using Illumina MiSeq chemistry. The abundance and diversity of bacteria in tissue and fecal samples were determined in relation to controls. Sparse logistic regression was calculated to predict the diagnosis of CD based on subject's microbiota profile. RESULTS: There were 17 children with CD and 18 controls. All children were Saudis. The median age was 13.9 and 16.3 years for children with CD and controls respectively. Sex distribution showed that 11/17 (65%) of the CD and 12/18 (67%) of the control subjects were boys. The mean area under the curve (AUC) was significantly higher in stool (AUC = 0.97 ± 0.029) than in tissue samples (AUC = 0.83 ±0.055) (P < 0.001). CONCLUSIONS: We found high AUC in mucosal and fecal samples. The higher AUC for fecal samples suggests higher accuracy in predicting the diagnosis of CD.

Regional variation of pediatric inflammatory bowel disease in Saudi Arabia: Results from a multicenter study.

BACKGROUND: Incidence and severity variations of inflammatory bowel disease (IBD) have been reported from Western populations between continents and regions of the same countries. However, no data were available from other countries. AIM: To investigate the regional differences in the IBD profiles of pediatric patients from the Kingdom of Saudi Arabia. METHODS: Data from a national multicenter IBD study were used. The incidence, time trend, and clinical presentation of Crohn's disease (CD) and ulcerative colitis (UC) in the Central region (CR), Western region (WR), and Eastern region (ER) were analyzed and compared. Statistical analysis included Poisson regression analysis for incidence variation and Chi-square test for demographic and clinical parameters. A P < 0.05 was considered significant. RESULTS: The prevalence of positive family history was lower in children with CD from the ER than the CR or the WR. Consanguinity rate was higher in children with CD and UC from the CR and the ER, respectively. The incidences and time trends of CD and UC were not significantly different between regions. In the ER, a significantly higher percentage of children with CD presented with abdominal pain (P < 0.001), blood in stools (P = 0.048), stricturing or penetrating disease (P = 0.029), higher erythrocyte sedimentation rate (P < 0.001), higher C-reactive protein (P < 0.001), higher anemia (P = 0.017), and lower albumin level (P = 0.014). For children with UC from the ER, a significantly higher percentage presented with anemia (P = 0.006) and a lower percentage with pancolitis (P < 0.001). CONCLUSION: The most important finding is the identification of significantly more severe presentation of CD in the ER of the Kingdom of Saudi Arabia. Prospective studies are needed to explain such variations.

Diagnostic delay of pediatric inflammatory bowel disease in Saudi Arabia.

BACKGROUND/AIM: Delay in the diagnosis of inflammatory bowel disease (IBD) is associated with complications. Our aim was to describe the pattern and risk factors associated with delay in the diagnosis of IBD in Saudi children. PATIENTS AND METHODS: This was a multicenter study with a retrospective/prospective design. Data on diagnostic delay in children with Crohn's disease (CD) and ulcerative colitis (UC) were retrieved from physician's notes. Multivariate regression analysis was used to assess the risk factors associated with long delay in diagnosis. RESULTS: There were 240 and 183 Saudi children with CD and UC, respectively. The median delays in diagnosis were 8 and 5 months in CD and UC, respectively, significantly longer in children with CD than UC (P < 0.001). Long diagnostic delays (>75th percentile) were 24 and 8.8 months for CD and UC, respectively. Ileal location was a significant risk factor in CD and the age of onset above 10 years was protective in UC. CONCLUSIONS: Long diagnostic delay in IBD was mainly due to the longer delay in gastroenterologist consultation. Review of the referral system is needed to focus on measures to reduce long delays in diagnosis. The ileal location as a risk factor in CD and age older than 10 years as protective in UC should help recognition and early referral.

Microbiota profile in new-onset pediatric Crohn's disease: data from a non-Western population.

BACKGROUND: The role of microbiota in Crohn's disease (CD) is increasingly recognized. However, most of the reports are from Western populations. Considering the possible variation from other populations, the aim of this study was to describe the microbiota profile in children with CD in Saudi Arabia, a non-Western developing country population. RESULTS: Significantly more abundant genera in children with CD included Fusobacterium, Peptostreptococcus, Psychrobacter, and Acinetobacter; whereas the most significantly-depleted genera included Roseburia, Clostridium, Ruminococcus, Ruminoclostridium, Intestinibacter, Mitsuokella, Megasphaera, Streptococcus, Lactobacillus, Turicibacter, and Paludibacter. Alpha diversity was significantly reduced in stool (p = 0.03) but not in mucosa (p = 0.31). Beta diversity showed significant difference in community composition between control and CD samples (p = 0.03). CONCLUSION: In this developing country, we found a pattern of microbiota in children with CD similar to Western literature, suggesting a role of recent dietary lifestyle changes in this population on microbiota structure.

Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease.

AIM: To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn's disease (CD). METHODS: Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer's protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated. RESULTS: All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (P < 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION: We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD.

Pre-illness diet as risk factor in pediatric inflammatory bowel disease in Saudi Arabia.

BACKGROUND/AIM: Inflammatory bowel disease (IBD) is increasing in Saudi Arabia but there's little knowledge about its risk factors. Our aim is to investigate the dietary risk factors of this disease in Saudi children. PATIENTS AND METHODS: The children investigated for IBD were prospectively enrolled. Those with confirmed IBD were designated cases and the others were controls. The average food frequency intake at least 3 months before onset of illness was obtained by direct interview and recorded on a modified food frequency questionnaire. Fast food, sweet gaseous soft drinks, fruits, and vegetables were selected. Statistical analysis included descriptive statistics, multivariate logistic regression was used, and the odds ratio was calculated to report the statistical significance of the results. RESULTS: A total of 91 children, 52 IBD (38 CD, 14 UC) and 39 controls were enrolled. Consumption of fast food and sweet gaseous drinks was more frequent in children with IBD than controls, whereas consumption of fruits and vegetables was less frequent in children with IBD. Only less fruits consumption was significantly associated with IBD as the odds of children getting IBD was 2.89 (1.06, 7.87). CONCLUSIONS: We report statistically significant positive association between less fruits consumption and IBD. Awaiting the results of larger sample size and more quantitative studies, the benefits of frequent fruit consumptions should be part of public health education.

Socioeconomic Impacts of Gluten-Free Diet among Saudi Children with Celiac Disease.

PURPOSE: To determine the socio-economic impact of gluten free diet (GFD) on Saudi children and their families. METHODS: A cross-sectional study was conducted in which an online questionnaire was sent to all families registered in the Saudi celiac patients support group. We included only children (age 18 years of age and younger) with biopsy-confirmed celiac disease (CD). RESULTS: A total of 113 children were included in the final analysis, the median age was 9.9 years; 62.8% were females. One hundred (88.5%) of the participating families reported that GFD food was not easily available in their areas, 17% of them reported that it was not available at all in their area. One hundred and six (93.8%) reported that the price of GFD food was very expensive and 70 (61.9%) families that the diet was heavily affecting their family budget. Significant social difficulties were reported among the participating families and their children including interference with the child's interaction with other children (49.6%), the families' ability to attend social gatherings (60.2%), the families' ability to eat in restaurants (73.5%), and the families' ability to travel (58.4%). CONCLUSION: There is significant negative socio-economic impact of GFD on children with CD & their families. Health care providers should be aware of these psycho-social difficulties and be well trained to provide a proper education and psychological support for these patients and their families.

The LMS and Z scale growth reference for Saudi school-age children and adolescents.

BACKGROUND/AIM: To establish L, M, and S parameters and z score reference for the assessment of nutrition and growth of Saudi school-age children and adolescents. SUBJECTS AND METHODS: Data from the original cross-sectional study were reanalyzed. The L, M, and S parameters and z scores were calculated for weight, height and body mass index for school-age children and adolescents. RESULTS: A total of 19,299 subjects from 5 to 18 years of age were included. All were Saudi nationals and 9,827 (50.9%) were boys. The L M S parameters and z scores for weight for age, height for age, and BMI for age for boys and girls are presented in detailed tables across the age of commonly used z scores (+3, +2, +1, 0, -1, -2, -3). Graphs corresponding to the same parameters (weight, height, and BMI) showing the main z scores across all ages from 5 to 18 years are illustrated. CONCLUSION: This report provides the first reference for nutritional status and growth of Saudi school-age children and adolescents. This tool is essential for more accurate assessment of growth and nutrition in various clinical conditions and research.

Impact of pediatric inflammatory bowel disease on linear growth: Data from a national cohort study in Saudi Arabia.

BACKGROUND/AIM: Linear growth impairment (LGI) is one of the most important features peculiar to children with inflammatory bowel disease (IBD). The aim of this report is to define the impact of IBD on the linear growth of children in the Kingdom of Saudi Arabia (KSA). SETTING AND DESIGN: Multicenter retrospective study. PATIENTS AND METHODS: Data from a cohort of newly- diagnosed children with IBD from 2003 to 2012 were analyzed retrospectively. The diagnosis of IBD was confirmed in accordance with the published criteria. Length/height for age was measured at diagnosis. The World Health Organization (WHO) reference was used and LGI was defined by length/height for age <-2 standard deviation. Chi-square test was used to test the significance of estimates and a P < 0.05 was considered significant. RESULTS: There were 374 children from 0.33 to 16 years of age, including 119 ulcerative colitis (UC) (32%), and 255 Crohn's disease (CD) (68%) patients. The prevalence of LGI was 26%, 28%, and 21% in IBD, CD, and UC, respectively. In children below 10 years, LGI was significantly more common in CD (P = 0.010), while in UC children, it was more common in older children (P = 0.011). CONCLUSION: This study demonstrates a prevalence of LGI consistent with that reported in the literature, but higher in CD children with early onset (<10 years) and in older children with UC, underscoring the importance of monitoring growth in children with IBD in the Saudi population. Prospective studies are needed to define the impact of IBD on growth velocity, puberty, and final adult stature.

Assessment of knowledge of celiac disease among health care professionals.

OBJECTIVES: To assess knowledge of celiac disease among medical professionals (physicians).   METHODS: We conducted a cross-sectional survey of hospital-based medical staff in primary, secondary, and tertiary care public, and private hospitals in Riyadh, Saudi Arabia (KSA). We carried out the study between January 2013 and January 2104 at King Khalid University Hospital, King Saud University, Riyadh, KSA. A pretested questionnaire was distributed to the potential participants. A scoring system was used to classify the level of knowledge of participants into 3 categories: poor, fair, and good.  RESULTS: A total of 109 physicians completed the survey and of these participants, 86.3% were from public hospitals, and 13.7% from private hospitals; 58.7% were males. Of the physicians, 19.2% had poor knowledge. Interns and residents had fair to good knowledge, but registrars, specialists, and even the consultants were less knowledgeable of celiac disease.   CONCLUSION: Knowledge of celiac disease is poor among a significant number of physicians including consultants, which can potentially lead to delays in diagnosis. Educational programs need to be developed to improve awareness of celiac disease in the health care profession.

Clinical Characteristics of Celiac Disease and Dietary Adherence to Gluten-Free Diet among Saudi Children.

PURPOSE: To describe the clinical characteristics of celiac disease (CD) among Saudi children and to determine the adherence rate to gluten free diet (GFD) and its determinant factors among them. METHODS: A cross-sectional study was conducted, in which all the families registered in the Saudi Celiac Patients Support Group were sent an online survey. Only families with children 18 years of age and younger with biopsy-confirmed CD were included. RESULTS: The median age of the 113 included children was 9.9 years, the median age at symptom onset was 5.5 years and the median age at diagnosis was 7 years, the median time between the presentation and the final diagnosis was 1 year. Sixty two of the involved children were females. Ninety two percent of the patients were symptomatic at the diagnosis while eight percent were asymptomatic. The commonest presenting symptoms included: chronic abdominal pain (59.3%), poor weight gain (54%), abdominal distention, gases, bloating (46.1%) and chronic diarrhea (41.6%). Sixty percent of the involved children were reported to be strictly adherent to GFD. Younger age at diagnosis and shorter duration since the diagnosis were associated with a better adherence rate. CONCLUSION: CD has similar clinical presentations among Saudi children compared to other parts of the ward; however, the adherence to GFD is relatively poor. Younger age at diagnosis and shorter duration since the diagnosis were associated with a better adherence rate.

Incidence of pediatric inflammatory bowel disease in Saudi Arabia: a multicenter national study.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) is increasingly recognized in developing countries; however, the incidence and trend over time have not been reported. METHODS: This retrospective study included children diagnosed with IBD in gastroenterology centers in the Kingdom of Saudi Arabia between 2003 and 2012. The date of birth, date and age at diagnosis, gender, and final diagnosis were collected on special forms. Clinical, laboratory, imaging, endoscopy, and histopathology results were reviewed to confirm the final diagnosis. Descriptive statistics were used to compare ulcerative colitis and Crohn's disease in different age groups, and significance was assessed by the chi-square test. Incidence rates and trend over time were analyzed with the assumption of Poisson distribution. The incidence rate over time was compared in 2 periods (2003-2007 and 2008-2012). A P value of <0.05 and 95% confidence intervals were used to assess the significance and precision of the estimates. RESULTS: A total of 340 Saudi Arabian children aged 0 to 14 years were diagnosed. The mean incidence rate per 100,000 individuals was 0.2, 0.27, and 0.47 for ulcerative colitis, Crohn's disease, and IBD, respectively. Except for the 0- to 4-year age group, there was a significant increase in incidence over time. CONCLUSIONS: Although the incidence of pediatric IBD in Saudi Arabian children is lower than suggested in the Western literature, there is a significantly increasing trend over time. However, decreased trend in the younger age group over time is identified. Prospective studies will be important to identify the risk factors for IBD in different age groups.

Menetrier`s disease in a Saudi child.

Menetrier`s disease is a rare form of acquired gastropathy that presents mostly during adulthood, but is extremely rare in children. It is a clinicopathological diagnosis that typically presents with abdominal pain, vomiting, and edema secondary to hypoalbuminemia. Endoscopy usually shows giant gastric mucosal folds, and gastric biopsy shows foveolar hyperplasia and decreased oxyntic glands. Here, we describe a 5-year-old boy from Saudi Arabia with typical presentation of Menetrier`s disease and serological evidence of acute cytomegalovirus infection.

Regional prevalence of short stature in Saudi school-age children and adolescents.

OBJECTIVE: To assess the magnitude of regional difference in prevalence of short stature in Saudi children and adolescents. SUBJECTS AND METHODS: A representative sample from three different regions of the Kingdom of Saudi Arabia (KSA) (North, Southwest, and Center) was used to calculate the prevalence of short stature (standard deviation score less than -2) in children 5 to 17 years of age. RESULTS: There were 9018 children and adolescents from 5 to 17 years of age (3366, 2825, and 2827 in the Northern, Southwestern and Central regions, resp.) and 51% were boys. In both school-age children and adolescents, there was a significantly higher prevalence of short stature in the Southwestern than in the Northern or the Central region (P < 0.0001). CONCLUSION: The finding of significant regional variation between regions helps in planning priorities for research and preventive measures.

Presenting features of childhood-onset inflammatory bowel disease in the central region of Saudi Arabia.

OBJECTIVE: To investigate the presenting features of childhood-onset inflammatory bowel disease (IBD) in the central region of Riyadh, Saudi Arabia and to compare with those reported in the literature. METHODS: This is a retrospective review of medical records of children below 18 years of age at onset of symptoms with confirmed diagnosis of IBD for age, gender, family history, presenting clinical and laboratory findings in the Divisions of Pediatric and Adult Gastroenterology, King Khalid University Hospital (which provides free health care) and the Department of Gastroenterology Al Mofarreh Poly Clinic, Riyadh, Saudi Arabia, between January 1993 and December 2010. RESULTS: Two hundred and eighteen children diagnosed with IBD with predominance of males in Crohn's disease (CD) (56%) and females in ulcerative colitis (UC) (59%). There was no significant difference between UC and CD regarding age of onset of symptoms (p=0.347); however, the difference in the age at presentation and age at final diagnosis were significant (p=0.027 and p=0.008). There was a significant increase of IBD diagnosis from the period 1993-2001 to 2002-2010 (p<0.0001). The family history was positive in 15.3%. CONCLUSION: The presenting clinical features and laboratory abnormalities are similar to those reported in other populations. Further studies are needed to establish the incidence and prevalence.

Regional variation in prevalence of overweight and obesity in Saudi children and adolescents.

BACKGROUND/AIMS: There are limited data on regional variation of overweight and obesity in the Kingdom of Saudi Arabia. Therefore, the aim of this report is to explore the magnitude of these variation in order to focus preventive programs to regional needs. SETTING AND DESIGN: Community-based multistage random sample of representative cohort from each region. PATIENTS AND METHODS: the study sample was cross-sectional, representative of healthy children and adolescents from 2 to 17 years of age. Body mass index (BMI) was calculated according to the formula (weight/height²). The 2000 center for disease control reference was used for the calculation of prevalence of overweight and obesity defined as the proportion of children and adolescents whose BMI for age was above 85 th and 95 th percentiles respectively, for Northern, Southwestern and Central regions of the Kingdom. Chi-square test was used to assess the difference in prevalence between regions and a P value of <0.05 was considered significant. RESULTS: The sample size was 3525, 3413 and 4174 from 2-17 years of age in the Central, Southwestern and Northern regions respectively. The overall prevalence of overweight was 21%, 13.4% and 20.1%, that of obesity was 9.3%, 6% and 9.1% in the Central, Southwestern and Northern regions respectively indicating a significantly-lower prevalence in the Southwestern compared to other regions (P<0.0001). CONCLUSIONS: This report revealed significant regional variations important to consider in planning preventive and therapeutic programs tailored to the needs of each region.

Prevalence of short stature in Saudi children and adolescents.

BACKGROUND AND OBJECTIVE: Data on stature in Saudi children and adolescents are limited. The objective of this report was to establish the national prevalence of short stature in Saudi children and adolescents. DESIGN AND SETTING: Community-based, cross-sectional study conducted over 2 years (2004, 2005) PATIENTS AND METHODS: The national data set of the Saudi reference was used to calculate the stature for age for children and adolescents 5 to 18 years of age. Using the 2007 World Health Organization (WHO) reference, the prevalence of moderate and severe short stature was defined as the proportion of children whose standard deviation score for stature for age was less than -2 and -3, respectively. In addition, the 2000 Center for Disease Control (CDC) and the older 1978 National Center for Health Statistics (NCHS)/WHO references were used for comparison. RESULTS: Using the 2007 WHO reference, sample size in the Saudi reference was 19 372 healthy children and adolescents 5 to 17 years of age, with 50.8% being boys. The overall prevalence of moderate and severe short stature in boys was 11.3% and 1.8%, respectively; and in girls, 10.5% and 1.2%, respectively. The prevalence of moderate short stature was 12.1%, 11% and 11.3% in boys and 10.9%, 11.3% and 10.5% in girls when the 1978 WHO, the 2000 CDC and the 2007 WHO references were used, respectively. CONCLUSIONS: The national prevalence of short stature in Saudi children and adolescents is intermediate compared with the international level. Improvement in the socioeconomic and health status of children and adolescents should lead to a reduction in the prevalence of short stature.