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.

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.

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.

Trends in infant nutrition in Saudi Arabia: compliance with WHO recommendations.

BACKGROUND AND OBJECTIVE: The WHO recommends exclusive breastfeeding in the first 6 months of life. Our objective was to evaluate trends in infant nutrition in Saudi Arabia and the degree of compliance with WHO recommendations. SUBJECTS AND METHODS: A nationwide nutritional survey of a sample of Saudi households was selected by the multistage probability sampling procedure. A validated questionnaire was administered to mothers of children less than 3 years of age. RESULTS: Of 5339 children in the sample, 4889 received breast milk at birth indicating a prevalence of initiation of 91.6%. Initiation of breastfeeding was delayed beyond 6 hours after birth in 28.1% of the infants. Bottle feeding was introduced by 1 month of age to 2174/4260 (51.4%) and to 3831/4260 (90%) by 6 months of age. The majority of infants 3870/4787 (80.8%) were introduced to "solid foods" between 4 to 6 months of age and whole milk feedings were given to 40% of children younger than 12 months of age. CONCLUSIONS: The current practice of feeding of Saudi infants is very far from compliance with even the most conservative WHO recommendations of exclusive breastfeeding for 4 to 6 months. The high prevalence of breastfeeding initiation at birth indicates the willingness of Saudi mothers to breastfeed. However, early introduction of complementary feedings reduced the period of exclusive breastfeeding. Research in infant nutrition should be a public health priority to improve the rate of breastfeeding and to minimize other inappropriate practices.

Blood pressure standards for Saudi children and adolescents.

BACKGROUND AND OBJECTIVES: Blood pressure levels may vary in children because of genetic, ethnic and socioeconomic factors. To date, there have been no large national studies in Saudi Arabia on blood pressure in children.Therefore, we sought to establish representative blood pressure reference centiles for Saudi Arabian children and adolescents. SUBJECTS AND METHODS: We selected a sample of children and adolescents aged from birth to 18 years by multi-stage probability sampling of the Saudi population. The selected sample represented Saudi children from the whole country. Data were collected through a house-to-house survey of all selected households in all 13 regions in the country. Data were analyzed to study the distribution pattern of systolic (SBP) and diastolic blood pressure (DBP) and to develop reference values. The 90th percentile of SBP and DBP values for each age were compared with values from a Turkish and an American study. RESULTS: A total of 16 226 Saudi children and adolescents from birth to 18 years were studied. Blood pressure rose steadily with age in both boys and girls. The average annual increase in SBP was 1.66 mm Hg for boys and 1.44 mm Hg for girls. The average annual increase in DBP was 0.83 mm Hg for boys and 0.77 mm Hg for girls. DBP rose sharply in boys at the age of 18 years. Values for the 90th percentile of both SBP and DBP varied in Saudi children from their Turkish and American counterparts for all age groups. CONCLUSION: Blood pressure values in this study differed from those from other studies in developing countries and in the United States, indicating that comparison across studies is difficult and from that every population should use their own normal standards to define measured blood pressure levels in children.

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.

Trends in the nutritional status of Saudi children.

OBJECTIVE: To evaluate the trend in the nutritional status of Saudi children over a 10-year period. METHODS: The growth data collected between 1993--1994 were compared with those collected between 2004--2005 from all regions of the Kingdom. Both nutritional surveys had a similar design leading to representative samples of Saudi children determined by multistage probability sampling. Similar methodology of measurements of the weight and height were used. The data from the 1994 study, including the third, fifth, fiftieth, ninety-fifth, and the ninety-seventh percentiles, were plotted on the 2005 charts for the weight for age, height for age, weight for height. RESULTS: Compared to the 1994 results, the data of the 2005 study indicate an upward shift of the lower percentiles of the weight for age, and the weight for height, more than height for age, indicating improved nutritional status. However, the upward shift of the higher percentiles for the weight for age, and weight for height in the 2005 survey, indicate increased trend for overweight and obesity. CONCLUSION: There is a demonstrable improvement in the nutritional status of Saudi children, and also tendency toward overweight and obesity over the last decade.

Prevalence of type 1 diabetes mellitus in Saudi Arabian children and adolescents.

OBJECTIVE: To determine the prevalence of type 1 diabetes mellitus among 0-19 years old Saudi children and adolescents. METHODS: A nationwide Saudi Arabian project was conducted in the years 2001-2007 with the objective of establishing national growth charts, and defining the prevalence of some chronic childhood diseases such as diabetes mellitus. The 14,000 households were randomly selected based on a recent population statistic. The questionnaire used included demographic data and evidence of diabetes mellitus. The prevalence was estimated and expressed per 100,000. Breakdown of this figure per age and region was carried out. RESULTS: In the 11,874 out of the 14,000 84.9% selected households, 45,682 children and adolescents were surveyed. Fifty children and adolescents were identified to have type 1 diabetes mellitus with a prevalence rate of 109.5 per 100,000. The male to female ratio was almost equal (26 males and 24 females). The distribution of prevalence of type 1 diabetes mellitus by region shows that the highest was 162 in the central region, and the lowest was 48 in the eastern region. Children and adolescents were also grouped by age into 5-6 (prevalence 100), 7-12 (prevalence 109), 13-16 (prevalence 243), and 17-18 (prevalence 150). CONCLUSION: We conclude that the prevalence of type 1 diabetes mellitus in Saudi Arabian children and adolescents is 109.5 per 100,000.

The prevalence of sickle cell disease in Saudi children and adolescents. A community-based survey.

OBJECTIVE: To determine the prevalence and regional distribution of sickle cell disease in Saudi children. METHODS: A sample size of 45,682 children and adolescents from newborn to 19 years of age was selected by multistage random probability sampling of the Saudi households from each of the 13 regions of the country. The study is cross-sectional, community based, and conducted over 2 years from 2004 to 2005. Data, including history and clinical examination were collected with house-to-house survey of all selected households. Data management and analysis was carried out at King Saud University, Riyadh, Saudi Arabia. RESULTS: Sickle cell disease was detected in 108 of 45,682 children and adolescents with a prevalence of 24 per 10,000. The regional distribution of sickle cell disease showed eastern region dominance with a prevalence of 145 per 10,000, followed by the southern region with a prevalence of 24 per 10,000, western region 12 per 10,000, and central region with 6 per 10,000. No cases were found in the northern regions. The male to female ratio was approximately 1:1. CONCLUSION: The results of this national wide community-based survey show a high prevalence of sickle cell disease in the community and the disease is more common in eastern and southern regions of the country. National or regional newborn screening programs for sickle cell disease using hematological tests should be planed. This study shows that the population at risk has an uneven geographical distribution. For this reason, selective rather than universal neonatal screening is likely to be more appropriate in the country.

Consanguinity and major genetic disorders in Saudi children: a community-based cross-sectional study.

BACKGROUND AND OBJECTIVES: There is a high rate of consanguinity in Saudi Arabia; however, information on its relationship with genetic disorders is limited. The objective of this cross-sectional study was to explore the role of consanguinity in genetic disorders. SUBJECTS AND METHODS: The study sample was determined by a multistage probability random sampling procedure. Consanguinity status was obtained during household visits. Primary care physicians performed a history and physical examination of all children and adolescents younger than 19 years, and all cases of genetic diseases were recorded. The chi-square test was used to compare proportions. RESULTS: During the two-year study period (2004-2005), 11 554 of 11 874 (97%) mothers answered the question on consanguinity, and 6470 of 11 554 (56%) were consanguineous. There was no significant association between first-cousin consanguinity and Down syndrome (P=.55). Similarly, there was no significant association with either sickle cell disease (P=.97) or glucose-6-phosphate dehydrogenase deficiency (P=.67) for first-cousin consanguinity. A borderline statistical significance was found for major congenital malformations (P=.05). However, the most significant association with first-cousin consanguinity was congenital heart disease (CHD) (P=.01). Finally, no significant association was found for type 1 diabetes mellitus (P=.92). For all types of consanguinity, similar trends of association were found, with a definite statistically significant association only with CHD (P=.003). CONCLUSION: The data suggest a significant role of parental consanguinity in CHD. However, a relationship between consanguinity and other genetic diseases could not be established. The effect of consanguinity on genetic diseases is not uniform and this should be taken into consideration in genetic counseling.

Comparison of the 2005 growth charts for Saudi children and adolescents to the 2000 CDC growth charts.

BACKGROUND AND OBJECTIVES: The 2000 CDC growth charts for the United States, a revision of the National Center for Health Statistics/World Health Organization (NCHS/WHO) growth charts, were released in 2002 to replace the NCHS/WHO charts. We evaluated the differences between the CDC growth charts and the Saudi 2005 reference to determine the implications of using the 2000 CDC growth charts in Saudi children and adolescents. SUBJECTS AND METHODS: The Saudi reference was based on a cross-sectional representative sample of the Saudi population of healthy children and adolescents from birth to 19 years of age. Measurements of the length/stature, weight and head circumference were performed according to expert recommendations. The CDC charts from birth to 20 years were based on a cross-sectional representative national sample from five sources collected between 1963 and 1994. The data from the CDC study including the 3rd, 5th, 50th, 95th, and 97th percentiles were plotted against the corresponding percentiles on the Saudi charts for the weight for age, height for age, weight for height for children from 0 to 36 months and weight for age, stature for age and body mass index for children 2 to 19 years of age. RESULTS: There were major differences between the two growth charts. The main findings were the upward shift of the lower percentiles of the CDC curves and the overlap or downward shift of the upper percentiles, especially for weight, weight for height, and BMI. CONCLUSION: The use of the 2000 CDC growth charts for Saudi children and adolescents increases the prevalence of undernutrition, stunting, and wasting, potentially leading to unnecessary referrals, investigations and parental anxiety. The increased prevalence of overweight and obesity is alarming and needs further investigation.

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.

Growth charts for Saudi children and adolescents.

OBJECTIVE: To establish reference growth charts for Saudi children and adolescents. METHODS: Multi-stage probability sampling of a cross-section of Saudi children and adolescents residing in all 13 regions of the Kingdom. Family interviews, and physical examinations of children and adolescents from birth to 19 years of age were conducted over a 2-year period (2004-2005). Only healthy children and adolescents were included for the measurement of length/stature, weight, and head circumference. All measurements were performed by trained physicians and nurses according to World Health Organization guidelines. Percentile construction and smoothing were performed using the LMS (lambda, mu, sigma) methodology. RESULTS: Determination of the standard measures for normal physical growth in a sample representing healthy Saudi children and adolescents from birth to 19 years of age. CONCLUSION: The results of this study present the most comprehensive and up-to-date reference growth charts for Saudi children and adolescents. Therefore, the authors recommend the use of these charts to replace older charts or those belonging to other countries.

Regional variations in the prevalence of consanguinity in Saudi Arabia.

OBJECTIVE: To report on the prevalence of consanguinity in each region of the Kingdom of Saudi Arabia including the variation in prevalence between urban and rural settlements. METHODS: The study was conducted over 2 years (2004-2005). A cross-sectional sample determined by multistage random probability sampling of Saudi households from each of the 13 regions of the Kingdom. As part of survey questionnaire, the mother of each household was asked on the relationship to her husband to choose one of 3 answers: first-degree cousin, more distant relationship, or no relation. RESULTS: The overall prevalence of consanguinity was 56% with the first-degree cousin (33.6%) being more common than all other relations (22.4%). The overall prevalence was significantly more common in rural (59.5%) than in urban settlements (54.7%) (p=0.000). There are regions with high prevalence of 67.2% such as Madina, and regions with significantly lower prevalence of 42.1% such as Al-Baha (p=0.000). CONCLUSION: The national prevalence of consanguinity in the Kingdom of Saudi Arabia remains high. In addition, there are significant variations in the prevalence of consanguinity between certain regions as well as between rural and urban settlements that should be taken into consideration in further studies.

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.

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.