Digital Health for Supporting Precision Medicine in Pediatric Endocrine Disorders: Opportunities for Improved Patient Care.

Digitalization of healthcare delivery is rapidly fostering development of precision medicine. Multiple digital technologies, known as telehealth or eHealth tools, are guiding individualized diagnosis and treatment for patients, and can contribute significantly to the objectives of precision medicine. From a basis of "one-size-fits-all" healthcare, precision medicine provides a paradigm shift to deliver a more nuanced and personalized approach. Genomic medicine utilizing new technologies can provide precision analysis of causative mutations, with personalized understanding of mechanisms and effective therapy. Education is fundamental to the telehealth process, with artificial intelligence (AI) enhancing learning for healthcare professionals and empowering patients to contribute to their care. The Gulf Cooperation Council (GCC) region is rapidly implementing telehealth strategies at all levels and a workshop was convened to discuss aspirations of precision medicine in the context of pediatric endocrinology, including diabetes and growth disorders, with this paper based on those discussions. GCC regional investment in AI, bioinformatics and genomic medicine, is rapidly providing healthcare benefits. However, embracing precision medicine is presenting some major new design, installation and skills challenges. Genomic medicine is enabling precision and personalization of diagnosis and therapy of endocrine conditions. Digital education and communication tools in the field of endocrinology include chatbots, interactive robots and augmented reality. Obesity and diabetes are a major challenge in the GCC region and eHealth tools are increasingly being used for management of care. With regard to growth failure, digital technologies for growth hormone (GH) administration are being shown to enhance adherence and response outcomes. While technical innovations become more affordable with increasing adoption, we should be aware of sustainability, design and implementation costs, training of HCPs and prediction of overall healthcare benefits, which are essential for precision medicine to develop and for its objectives to be achieved.

Blood pressure standards for pre-school children in Saudi Arabia.

The prevalence of hypertension (HTN) in children is increasing. Early detection of HTN in childhood may prevent the occurrence of complications in adult age. Blood pressure (BP) varies between populations according to ethnic and environmental factors. Based on these variations, reference norms developed for one particular population may not be applicable to others. Thus, this study aimed to provide age-, gender-, and height-related BP reference standards using oscillometric techniques for pre-school children in Saudi Arabia. A sub-sample of preschool children aged from 2 to 6 years was selected by multi-stage probability sampling of Saudi population. The samples 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. Oscillometric devices were used to measure the BP. Data were analyzed to study the distribution pattern of systolic (SBP) and diastolic BP (DBP) and to develop reference values based on age, gender, and height. The values for each age and height percentile were compared with the recent (2017) values of the North American children. A total of 2553 Saudi Arabian children (1299 boys and 1254 girls) aged 2-6 years with complete data on age, gender, height, SBP, and DBP were considered for analysis. Values for SBP and DBP were significantly higher in Saudi children than in the North American children. This study adds evidence to the BP variations between populations with influences such as genetic and environmental factors. The need of every population to define its normal BP standards is essential to avoid unnecessary investigations and anxiety in patients and their parents.

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.

Diagnosis and management of growth disorders in Gulf Cooperation Council (GCC) countries: Current procedures and key recommendations for best practice.

Diagnosis and management of growth disorders comprises an important area of pediatric practice. Current procedures in the different stages of the identification, referral, investigation, and treatment of growth disorders in the Gulf Cooperation Council (GCC) countries have been summarized. Evidence-based procedures, relating specifically to height screening for identification of short stature, auxological criteria for patient referral from primary to secondary pediatric care, and general and endocrine investigations and diagnosis have been discussed and outlined. The management issues related to key disorders that are licensed for growth hormone (hGH) therapy, namely GH deficiency, Turner syndrome, short stature related to birth size small for gestational age (SGA), and idiopathic short stature are discussed with recommendations described for best practice. Finally, two key components of short stature management, namely transitional care for the transfer of patients from pediatric to adult endocrinology services and adherence to recommended therapy with hGH, have been addressed with current practice outlines and recommendations presented.

Growth hormone therapy and treatment outcomes: current clinical practice of the Gulf Cooperation Council.

Over the last 20 years, recombinant human growth hormone (somatropin) has been the cornerstone of managing children with growth hormone deficiency (GHD). Although both international and national guidelines for growth hormone (GH) therapy exist, there is currently no consensus on the optimal use of GH therapy in Gulf Cooperation Council (GCC) countries. The goals of GH therapy are to normalize height during childhood, attain normal adult height and correct metabolic abnormalities related to GHD. However, extended use of GH >50 µg/kg/day may increase frequency of adverse events. Here, we report the proceedings from a meeting of nine GCC pediatric endocrinology experts, which took place in Beirut in November 2011. The meeting was also attended by three European counterparts and aimed to provide consensus on best practice in the management of children with GHD in the GCC based on current local medical and regulatory environments.

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.

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.

The prevalence of neurological disorders in Saudi children: a community-based study.

There are limited data on the pattern and prevalence of pediatric chronic neurologic conditions in the region. Therefore, the objective of this study was to establish the prevalence of these disorders in the Kingdom of Saudi Arabia. A multistage probability sampling design was used to select a random sample of Saudi households representative of the Saudi population. A total of 45 682 Saudi children were screened. Of these children, 313 had a chronic major neurologic disorder indicating a prevalence of 68.5 per 10 000 children, which was the highest among all chronic diseases in children. Mental retardation and cerebral palsy were the most common neurologic disorders among Saudi children with a prevalence rate of 26.3/10 000 and 23.4/10 000, respectively. The finding that major neurologic disorders are the most common pediatric chronic disorders in the Kingdom of Saudi Arabia indicates that priority should be given to research and education as well as health care planning.

Prevalence of malnutrition in Saudi children: a community-based study.

BACKGROUND AND OBJECTIVE: There is no published information on the prevalence of malnutrition in Saudi Arabia. The objective of this study was to establish the prevalence data. METHODS: The prevalence of nutritional indicators in the form of underweight, stunting, and wasting in a national sample of children younger than 5 years of age was calculated using the new WHO standards as reference. Calculations were performed using the corresponding WHO software. The prevalence of moderate and severe underweight, wasting and stunting, was defined as the proportion of children whose weight for age, weight for height, and height for age were below -2 and -3 standard deviation scores, respectively. RESULTS: The number of children younger than 5 years of age was 15 516 and 50.5% were boys. The prevalence of moderate and severe underweight was 6.9% and 1.3%, respectively. The prevalence of moderate and severe wasting was 9.8% and 2.9%, respectively. Finally, the prevalence of moderate and severe stunting was 10.9% and 2.8%, respectively. The prevalence was lower in girls for all indicators. Comparison of the prevalence of nutritional indicators in selected countries demonstrates large disparity with an intermediate position for Saudi Arabia. CONCLUSION: This report establishes the national prevalence of malnutrition among Saudi children. Compared to data from other countries, these prevalence rates are still higher than other countries with less economic resources, indicating that more efforts are needed to improve the nutritional status of children.

Regional disparity in prevalence of malnutrition in Saudi children.

OBJECTIVE: To evaluate the regional difference in the prevalence of malnutrition in Saudi children. METHODS: Data for this study were collected over 2 years (2004 and 2005). A cross-sectional representative sample of the Saudi population of healthy children below 5 years of age was used to calculate the prevalence of malnutrition. The study was carried out in the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia. Body measurements of the weight, length, and height were performed according to standard recommendations. Standard deviation scores were determined using the Lambda, Mu, and Sigma (LMS) statistical methodology. The 1978 NCHS/WHO growth reference was used for the calculation of prevalence of underweight, wasting, and stunting defined as the proportion of children whose weight for age, weight for height, and height for age was below minus standard deviation (-2 SD) for Northern, Southwestern, and Central regions of the Kingdom of Saudi Arabia. Chi-square test was used to assess the difference in prevalence between regions, and a p<0.05 was considered significant. RESULTS: The sample size of children <5 years of age in Central region was 5067, Southwestern 2285, and Northern 2933. The prevalence of underweight was 4%, 19.7% and 5.5%, that of wasting was 6.5%, 16.7% and 6.5% and of stunting was 6.4%, 13.2% and 6.4% in the Central, Southwestern, and Northern regions indicating a significantly-higher prevalence in Southwestern compared to other regions (p<0.001). CONCLUSION: This report revealed a high prevalence of significant nutritional indicators in the Southwestern regions than in other regions. This finding indicates that this region should be given priority for further studies to identify causes, and to design health promotion programs.

Prevalence of overweight and obesity in Saudi children and adolescents.

BACKGROUND AND OBJECTIVE: There is limited information on overweight and obesity in Saudi children and adolescents. The objective of this study was to establish the national prevalence of overweight and obesity in Saudi children and adolescents. METHODS: The 2005 Saudi reference data set was used to calculate the body mass index (BMI) for children aged 5 to 18 years. Using the 2007 WHO reference, the prevalence of overweight, obesity and severe obesity were defined as the proportion of children with a BMI standard deviation score more than +1, +2 and +3, respectively. The 2000 CDC reference was also used for comparison. RESULTS: There were 19 317 healthy children and adolescents from 5 to 18 years of age, 50.8% of whom were boys. The overall prevalence of overweight, obesity and severe obesity in all age groups was 23.1%, 9.3% and 2%, respectively. A significantly lower prevalence of overweight (23.8 vs 20.4; P<.001) and obesity (9.5 vs 5.7; P<.001) was found when the CDC reference was used. CONCLUSIONS: This report establishes baseline national prevalence rates for overweight, obesity and severe obesity in Saudi children and adolescents, indicating intermediate levels between developing and industrialized countries. Measures should be implemented to prevent further increases in the numbers of overweight school-age children and adolescents and the associated health hazards.

Effects of education of the head of the household on the prevalence of malnutrition in children.

OBJECTIVE: To explore the effect of the educational level of the head of household on the prevalence of malnutrition in Saudi children. METHODS: The study was conducted over 2 years in 2004 and 2005 in all regions of the Kingdom of Saudi Arabia (KSA). The design consisted of a stratified multistage probability random sampling of the population of the KSA. The educational level of the heads of the household, and measurements of weight and height of the children were obtained during house visits. Nutritional indicators in the form of weight for age, height for age, and weight for height for children below 5 years of age were determined, and the prevalence of each indicator below -2 standard deviations (SD) was calculated for each level of education. RESULTS: The sample size was 7390 in the weight for age, 7275 height for age, and 7335 for weight for height. The prevalence of underweight (weight for age below -2 SD) increased from 7.4% for the university level to 15.2% in the children of illiterate heads of household. Similar patterns were found for the prevalence of stunting (height for age below -2 SD) and wasting (weight for height below -2 SD). CONCLUSION: This study demonstrates that the higher the education level of the heads of the household, the lower the prevalence of malnutrition in their children, suggesting that completing at least 9-12 years of education (intermediate and secondary school) is needed for better improvement in the nutritional status of the children.

Pattern of sex differences in growth of Saudi children and adolescents.

BACKGROUND: Although variations in growth between boys and girls have been reported, detailed descriptions according to age and growth parameters are not available. OBJECTIVE: The goal of this study was to determine the pattern and magnitude of differences in growth between boys and girls according to age that justify separate growth charts. METHODS: The data set was based on a cross-sectional representative sample of the Saudi population of healthy children and adolescents from birth to 19 years of age. Body measurements (length, height, weight, and head circumference) were performed according to standard recommendations; body mass index was also determined for each subject. The difference in growth between boys and girls was assessed based on z scores and percentiles (5th, 50th, and 95th) of growth parameters using 2 age groups (0-3 years and 2-19 years). The significance of the difference between boys and girls for any growth parameter was tested by ANCOVA. RESULTS: A total of 35,279 children and adolescents from birth to 19 years of age satisfied the criteria for growth measurements. There were 17,880 boys and 17,399 girls; all were Saudi nationals. The Saudi boys were generally taller and heavier than girls up to approximately 7 to 10 years of age. Thereafter, girls generally were taller and heavier than boys from 10 to 14-15 years of age. After that, boys again were taller and heavier. Similar variations were observed for body mass index and head circumference. The difference between boys and girls for each growth parameter was highly significant (P < 0.001). CONCLUSIONS: Based on analysis of these Saudi children and adolescents, the difference in growth between boys and girls was not uniform but depended on age. However, the pattern was remarkably consistent across all growth parameters and appears to reflect the timing of maturation between boys and girls.

Regional variations in the growth of Saudi children and adolescents.

BACKGROUND AND OBJECTIVES: No previous study has provided a detailed description of regional variations of growth within the various regions of Saudi Arabia. Thus, we sought to demonstrate differences in growth of children and adolescents in different regions. SUBJECTS AND METHODS: The 2005 Saudi reference was based on a cross-sectional representative sample of the Saudi population of healthy children and adolescents from birth to 18 years of age. Body measurements of the length, stature, weight, head circumference and calculation of the BMI were performed according to standard recommendations. Percentile construction and smoothing were performed using the LMS (lambda, mu and sigma) methodology, followed by transformation of all individual measurements into standard deviation scores. Factors such as weight for age, height for age, weight for height, and head circumference for children from birth to 3 years, stature for age, head circumference and body mass index for children between 2-18 years of age were assessed. Subsequently, variations in growth between the three main regions in the north, southwest, and center of Saudi Arabia were calculated, with the Bonferroni: method used to assess the significance of differences between regions. RESULTS: There were significant differences in growth between regions that varied according to age, gender, growth parameter and region. The highest variation was found between children and adolescents of the southwestern region and those of the other two regions The regression lines for all growth parameters in children P =.001). However, the difference between the northern and central regions were not significant for the head circumference and for weight for length. For older children and adolescents a significant difference was found in all parameters except between the northern and central regions in BMI in girls and head circumference in boys. Finally, the difference in head circumference of girls between southwestern and northern regions was not significant. Such variation affected all growth parameters for both boys and girls. CONCLUSION: Regional variations in growth need to be taken into consideration when assessing the growth of Saudi children and adolescents.

Body mass index in Saudi Arabian children and adolescents: a national reference and comparison with international standards.

BACKGROUND AND OBJECTIVES: Because there are no reference standards for body mass index (BMI) in Saudi children, we established BMI reference percentiles for normal Saudi Arabian children and adolescents and compared them with international standards. SUBJECTS AND METHODS: Data from a stratified multistage probability sample were collected from the 13 health regions in Saudi Arabia, as part of a nationwide health profile survey of Saudi Arabian children and adolescents conducted to establish normal physical growth references. Selected households were visited by a trained team. Weight and length/height were measured and recorded following the WHO recommended procedures using the same equipment, which were subjected to both calibration and intra/interobserver variations. RESULTS: Survey of 11 874 eligible households yielded 35 275 full-term and healthy children and adolescents who were subjected to anthropometric measurements. Four BMI curves were produced, from birth to 36 months and 2 to 19 years for girls and boys. The 3rd , 5 th , 10th , 25th , 50th , 75th , 85th , 90th , 95th , and 97th percentiles were produced and compared with the WHO and CDC BMI charts. In the higher percentiles, the Saudi children differed from Western counterparts, indicating that Saudi children have equal or higher BMIs. CONCLUSION: The BMI curves reflect statistically representative BMI values for Saudi Arabian children and adolescents.

Age related reference ranges of heart rate for Saudi children and adolescents.

OBJECTIVE: To evaluate the resting heart rate to define reference values for healthy Saudi children and adolescents. METHODS: To establish representative heart rate (HR) reference values for Saudi Arabian children and adolescents, a sample of children, and adolescents was selected by multi-stage probability sampling of the Saudi population from birth to 20 years of age. The selected sample represents Saudi children from the whole country. Data were collected by a house-to-house survey of all selected households in all the 13 regions in the country. A total of 10,458 Saudi children were included in the study. The HR was measured by oscillometric-automated devices. Upper and lower reference values of the HR in boys and girls were calculated as mean +/= 2 SD. The study is cross-sectional, community based, and conducted over 2 years (2004-2005). Data management and analysis were performed in the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia. RESULTS: Determination of the HR values in a sample representing healthy Saudi children and adolescents from birth to 20 years of age. CONCLUSION: The present study provides age-specific reference values for heart rate (HR) of Saudi children and adolescents based on a large study sample. The use of these standards should aid the identification of children with abnormal HR.

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.

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.