Bacterial dysbiosis in newly diagnosed treatment naïve pediatric ulcerative colitis in Saudi Arabia.

BACKGROUND: The role of microbiota in the pathogenesis of ulcerative colitis (UC) has been increasingly recognized. However, most of the reports are from Western populations. In Middle Eastern countries, including Saudi Arabia, little is known about the role of microbiota. Therefore, our aim was to describe the bacterial microbiota profile and signature in pediatric UC in Saudi Arabia. METHODS: Twenty children with UC and 20 healthy controls enrolled in the study gave stool samples. Twenty rectal mucosal samples were taken from UC and 20 from non-UC controls. Inclusion criteria included newly diagnosed and untreated children and lack of antibiotic exposure for at least 6 months before stool collection was required for children with UC and controls. Bacterial deoxyribonucleic acid was extracted and sequenced using shotgun metagenomic analysis. Statistical analysis included Shannon alpha diversity metrics, Bray-Curtis dissimilarity, DESeq2, and biomarker discovery. RESULTS: The demographic characteristics were similar in children with UC and controls. There was a significant reduction in alpha diversity (P = 0.037) and beta diversity in samples from children with UC (P = 0.001). Many taxa were identified with log2 abundance analysis, revealing 110 and 102 species significantly depleted and enriched in UC, respectively. Eleven bacterial species' signatures were identified. CONCLUSIONS: In Saudi Arabian children with UC, we demonstrate a dysbiosis similar to reports from Western populations, possibly related to changes of lifestyle. Microbial signature discovery in this report is an important contribution to research, leading to the development of adjunctive non-invasive diagnostic options in unusual cases of UC.

Prevalence of functional gastrointestinal disorders in Saudi infants and toddlers: A cross-sectional multicenter study.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are common pediatric problems, but their prevalence in Saudi Arabia is unknown. We aimed to assess the prevalence of FGIDs and risk factors among children in six regions of Saudi Arabia. METHODS: This was a cross-sectional multicenter study enrolling children aged 0-48 months, attending pediatric clinics. Questionnaires evaluated the clinical history, symptoms, and sociodemographic information. FGIDs were defined according to Rome IV criteria. RESULTS: The study involved 1011 infants and toddlers (mean [standard deviation (SD)] aged, 21.7 [19.4] months; FGIDs and mean [SD] age 17.4 [16.4] months; controls). FGIDs were diagnosed in 483 (47.7%) of all infants and toddlers. The prevalence of FGIDs was significantly higher in children aged 0-12 months than in those aged 13-48 months ( P < 0.001). The most common disorders were functional regurgitation (13.8%) in infants and functional constipation (9.6%) in toddlers. Univariate regression analysis confirmed that the rate of FGIDs was higher in term gestational age infants (odds ratio (OR) 2.7; 95% confidence interval (CI), 1.76-4.17, P < 0.001), in partial breastfeeding (OR 0.58; 95% CI, 0.40-0.84, P = 0.003), in formula feeding (OR 2.25; 95% CI, 1.51-3.35, P < 0.001), and in subjects with no history of food allergy (OR 2.40; 95% CI, 1.58-3.64, P < 0.001). CONCLUSION: FGIDs are common in Saudi infants and toddlers (47.7%). Regurgitation is most prevalent in infants, and functional constipation is most common in toddlers. Term gestational age infant, partial breastfeeding, formula feeding, and subjects with no history of food allergy are associated with the prevalence of FGIDs.

Environmental Risk Factors for Childhood Inflammatory Bowel Diseases: A Multicenter Case-Control Study.

Objective: Multiple environmental factors can be linked to the development of inflammatory bowel disease (IBD).With an increase in the cases of IBD, the objective of this research is to investigate environmental risk factors for IBD in the Saudi population. Methods: A retrospective multicenter case−control study was performed among IBD children from 2009 to 2021.The variables analyzed to be the possible risk factors included their socioeconomic status, living and demographic characteristics, and lifestyle related to IBD. The questionnaire included a list of IBD risk factors that was given to the control and the patient group. For every variable, the 95% confidence interval (CI) and odds rations were also estimated. Results: There were 335 individuals considered in this study: 168 controls (50.1%) and 167 IBD patients (49.9%). Of these, 93 IBD patients (56%) had CD and 74 patients (44%) had UC. Most of participants were female (72.1%) and were aged above 10 years (51.5%). Vaginal delivery (OR 0.551, 95% CI: 1.59−4.14), age above 10 years (OR 1.040, 95% CI: 1.012−1.069), deficient fruit intake (OR 2.572, 95% CI: 1.59−4.14), no exposure to antibiotics (OR 2.396, 95% CI: 1.51−3.81), appendectomy (OR 2.098, 95% CI: 1.87−2.35), less physical activity (OR 2.033, 95% CI: 1.05−3.93) and gastroenteritis admissions > 2 times/year (OR 0.107, 95% CI: 0.037−0.311) were the risk factors for IBD. These factors depicted a more significant link with CD than UC (p < 0.05). Interestingly, sleep disturbance was estimated to be a CD risk factor (adjusted OR: 3.291, 95% CI = 0.97−11.22). Pets in house was risk factor for UC (p < 0.001). Conclusions: This study highlights association between vaginal delivery, age above 10 years, deficient fruit intake, low physical activity, exposure to antibiotics, appendectomy, and frequent gastroenteritis admissions as risk factors for IBD. Knowledge of these risk factors can help pediatricians to prospectively identify patients at risk of environmental exposure.

Tricho-hepato-enteric syndrome: Retrospective multicenter experience in Saudi Arabia.

Background: Trichohepatoenteric syndrome (THES) is a very rare disorder that is characterized by intractable congenital diarrhea, woolly hair, intrauterine growth restriction, facial dysmorphism, and short stature. Our knowledge of THES is limited due to the small number of reported cases. Methods: Thirty patients diagnosed with THES, all molecularly confirmed by whole exome sequencing (WES) to have biallelic variants in TTC37 or SKIV2L, were included in the study. Clinical, biochemical, and nutritional phenotypes and outcome data were collected from all participants. Results: The median age of THES patients was 3.7 years (0.9-23 years). Diarrhea and malnutrition were the most common clinical features (100%). Other common features included hair abnormalities (96%), skin hyperpigmentation (87%), facial dysmorphic abnormalities (73%), psychomotor retardation (57%), and hepatic abnormalities (30%). Twenty-five patients required parenteral nutrition (83%) with a mean duration of 13.34 months, and nearly half were eventually weaned off. Parenteral nutrition was associated with a poor prognosis. The vast majority of cases (89.6%) had biallelic variants in SKIV2L, with biallelic variants in TTC37 accounting for the remaining cases. A total of seven variants were identified in TTC37 (n = 3) and SKIV2L (n = 4). The underlying genotype influenced some phenotypic aspects, especially liver involvement, which was more common in TTC37-related THES. Conclusion: Our data helps define the natural history of THES and provide clinical management guidelines.

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.

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.

Knowledge and practice styles of pediatricians in Saudi Arabia regarding childhood constipation.

OBJECTIVES: The aim of the present study was to evaluate knowledge and practice styles among medical providers working in 5 regions of Saudi Arabia regarding their approach to childhood constipation. METHODS: A survey of 850 pediatric providers (PPs) conducted in 5 regions of Saudi Arabia. PPs included pediatric specialists (PSs), pediatric consultants (PCs), general practitioners (GPs), family physicians (FPs), and pediatric gastroenterologists (PGs). They were asked anonymously about definition, causes, diagnosis, and management of constipation. Information about family concerns regarding constipation and the source of constipation-related information was also collected. RESULTS: A response rate of 73% yielded 622 questionnaires. Among respondents, 61.2% were aware of the Rome definition of functional constipation. More pediatricians (PSs and PCs) than other physicians (GPs and FPs) reported the definition of constipation correctly (P > 0.05). Stool withholding was reported as the most common cause of constipation by 27% of pediatricians (PSs and PCs), 24% of other physicians (GPs and FPs), and 50% of PGs (P = 0.097). Rectal examination was performed by 39% of all PPs and 78.6% of PGs (P = 0.009). Pediatricians prescribed lactulose significantly more often than physicians (P = 0.001). Pediatricians recommended disimpaction before maintenance treatment significantly more than other physicians (P = 0.001). Twenty-three percent of families believed that constipation was caused by a stricture and 10% feared it was caused by a malignancy. CONCLUSIONS: Significant differences in knowledge and practice patterns exist regarding the approach to pediatric constipation. Identification of knowledge gaps may be useful to develop educational materials to improve proper diagnosis and treatment of childhood constipation.

Efficacy of a single dose intravenous heparin in reducing sheath-thrombus formation during diagnostic angiography: A randomized controlled trial.

BACKGROUND: Femoral arterial sheath thrombosis and distal embolization are well-recognized complications of cardiac catheterization but the occlusion is extremely rare. Heparinized saline flushes are used during diagnostic coronary angiography to prevent thrombus formation within the sheath lumen. However, the use of prophylactic intravenous heparin following the femoral arterial sheath insertion is controversial. The aim of this study is to evaluate the effectiveness of 2000 units of intravenous heparin bolus in comparison to a saline placebo on the thrombus formation within the arterial sheath during the diagnostic coronary angiography. METHODS: Eligible patients were randomized to receive either a study drug or placebo at the time of femoral sheath insertion. The sheath was aspirated and flushed for any presence of thrombus after each catheter exchange and at the end of the procedure. Five milliliters of blood were extracted and visualized on clean gauze followed by a saline flush. The primary end-point was the effectiveness of the study drug on reducing the incidence of sheath-thrombus formation. RESULTS: Three hundred and twenty patients were randomized into two arms. Three hundred and four patients were analyzed: 147 patients in heparin arm and 157 patients in placebo arm after exclusion of 13 patients in heparin arm and three in placebo arm because of incomplete reports. The baseline characteristics were similar and sheath-thrombi formation was observed in 20% of the total cohort. Of the heparin arm, 12% (19 patients) developed sheath-thrombus formation, whereas 26% (42 patients) in the placebo arm, p-value = 0.002. An adjusted logistic regression model showed that the only predictor for the sheath-thrombus formation was the study drug (i.e. heparin). The odds ratio of developing a thrombus in the control arm was 2.5 (95% CI: 1.4-4.5, p = 0.003). There were no bleeding events observed. CONCLUSION: The risk of thrombus formation is significant and intravenous heparin significantly reduced thrombus formation during diagnostic coronary angiography, with no excess bleeding events.