Long-term health consequences of central precocious/early puberty (CPP) and treatment with Gn-RH analogue: a short update.

BACKGROUND: The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors. METHODS: We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk. RESULTS: Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders. CONCLUSION: Monitoring and early diagnosis of these conditions are of paramount importance for successful management.

Qatar population-specific centile charts of placental weight in 80 722 newborns: relation to maternal age, gestational age, newborn birth weight, and gender, between the 37 th and 42 nd weeks of gestation.

BACKGROUND: Data about placental weight (PW) in relation to birth weight (BW) and gestational age (GA) are lacking in Arabic countries. AIMS OF THE STUDY: (a) to find out the national PW standards for babies born between 37th and 42nd weeks of gestation in male and female babies born in Qatar; (b) to study the relation, if any, between PW and maternal age, gestational age (GA), birth weight (BW), and gender of the newborn. MATERIALS AND METHODS: A National population-based retrospective chart review study was conducted between 1-2016 to 12-2019 (n = 80 722). Data of gestational age (GA) at delivery (in weeks), newborn birth weight (BW), PW, and gender at birth, were collected from singleton babies born between 37 th and 42nd weeks of gestation. RESULTS: The PW ranged from 440 to 860 grams (g) with a mean of 682 ± 96 g. at term for boys and 673 ± 94 g. for girls. The mean BW was 3 036 ± 448 g and BW/PW ratio was 0.203 ± 0.026. The PW continued to increase through 41 weeks' gestation, in boys and girls with a significant decrease at the 42nd week of gestation. PW was significantly correlated with BW (r = 0.596, P: < 0.001) and GA (r = 0.15, P: <0.001) and accounted for 43.4% of the explained variability in birth weight. CONCLUSIONS: PW was a significant predictor of BW with a consistent increase in PW until the 41st week of gestation in boys and girls and a positive correlation with BW and GA.

Nutritional studies in patients with ß-thalassemia major: A short review.

BACKGROUND: Patients with ß-thalassemia major (BTM) had variable prevalence of undernutrition and abnormal body composition.  Methods: We performed an electronic search in PubMed, Scopus, Research gate, and Web of Sciences to evaluate the prevalence of nutritional disorders in patients with BTM worldwide in relation to their body composition and possible etiological factors. In addition, we reviewed the published nutritional intervention studies.  Results: 22 studies on the prevalence of undernutrition (12 countries) and 23 nutritional intervention studies were analyzed.  Undernutrition occurred in a considerable number of patients but varied greatly among different countries (from 5.2% to 70%). The lower middle income (LMI) countries (India, Pakistan, Iran, Egypt) had higher prevalence, while (high -middle and high income (Turkey, Greece, North America, USA, Canada) had lower prevalence.  Even in patients with normal BMI, abnormalities of body composition are common with decreased muscle mass, lean-body mass, and bone mineral density. 65% to 75% of them had lower energy intake with low levels of circulating nutrients, minerals (zinc, selenium, and copper), and vitamins (D, E) versus controls. Increased macro and micronutrient requirements decreased absorption and /or increased loss or excretion are etiologic factors. Undernutrition was associated with short stature and lower quality of life (QOL). High prevalence of endocrinopathies, poor transfusion regimen (tissue hypoxia), improper chelation, and lack of maternal education, represented important risk factors in the production of poor growth in weight and stature. CONCLUSIONS: Timely detection of undernutrition in patients with BTM and proper nutritional intervention could prevent growth delay and comorbidities.

Postnatal Growth and Prevalence of Obesity in Infants Born Large-for-Gestational Age during the First 3 years of Life: Personal Experience and Exploration of Current Literature.

AIMS OF THE STUDY: We evaluated the growth patterns in a cohort of infants (n = 120) born large-for-gestational-age (LGA) [birth weight (Bwt) > 4 kg] from birth to age 3 years of age in comparison with normal age and sex-matched children (WHO). RESULTS: LGA infants had high weight for age Z score (WAZ) at birth that decreased significantly during the first 6 months of life (by a mean of - 0.67 SD) that was followed by significant gain during the following 6 months of life (around + 0.4 SD). These children grew on a higher centile of WAZ with no significant change during the second and third years of life.  The prevalence of obesity (WAZ > 2) increased markedly from 24% at the end of their first year to 34% and 36% at the end of their second and third years of life, respectively.  The mean length for age Z score (LAZ) decreased significantly during the first 6 months (by a mean of -0.9 SD) but was maintained at high centile (> 1 SD) during the second and 3rd years.  The weight for length SDS (WLZ) increased significantly during the first 18 months of life and decreases gradually during the second half of the 2nd year and the 3rd year.   Their head circumference SDS decreased significantly in the first 6 months and then sustained around the 70th centiles (+1 SD) in the following 18 months. CONCLUSION: Our study showed that in LGA babies obesity increased progressively after the first year of life to reach 36% at the end of the third year. Therefore, it is important to apply the early nutritional intervention to decrease the occurrence of obesity and reduce later cardiometabolic risks.

The long-term (five years) effects of prednisone therapy in children with frequently relapsing nephrotic syndrome: A controlled study of anthropometric parameters and metabolic abnormalities.

BACKGROUND: Steroids are the main drugs used for the treatment of nephrotic syndrome (NS) in children. AIM OF THE STUDY: We investigated the steroid effect on linear growth and weight gain as well as the prevalence of different metabolic components and dysglycemia in children with NS with multiple relapses for 5 years in relation to the cumulative dose of steroids. Study population and sample size: Data of 30 children with NS were analyzed retrospectively. They received prednisolone treatment as advised by international guidelines. The cumulative dose of prednisolone (CDP) over the 5 years was calculated for each child. Their growth and different metabolic criteria, including impaired fasting glucose (IFG), high LDL and cholesterol, lower HDL, and high blood pressure studied over this period and compared with the data for 66 age-matched obese non-nephrotic children. RESULTS: The mean CDP was 100 ± 63 mg /kg/yr given over an average duration of 5 years.  The height-SDS was not affected after 3 years but decreased by -0.4 SD after 5 years. The body mass index-SDS increased from 0.65 to 0.97 and 1.1 after 3 and 5 years, respectively. Obesity and overweight increased from 25% pre-treatment to 59.2% after 5 years of treatment. After 5 years of treatment, IFG was detected in 35 %, hypertension in 40%, high LDL in 77%, and high cholesterol in 80%. CONCLUSION: In children with frequently relapsing NS, long-term steroid therapy was associated with a higher rate of obesity, short stature as well as the occurrence of different metabolic syndrome (MetS.

Linear growth and prevalence of the different components of the metabolic syndrome (MetS) in young obese nondiabetic children (below 5 years) in comparison to older obese children (6-12 years).

BACKGROUND: In Qatar, the prevalence of metabolic syndrome (MetS) in children and adults is increasing in parallel with the markedly increasing trends in obesity rates. OBJECTIVE: The aim of our study was to assess the prevalence of different components of MetS, measure plasma atherogenic indexes (AIP), and to evaluate linear growth in young obese nondiabetic children (< 5 years) in comparison to older obese children (6-12 years).  Methods:  We analysed the anthropometric and biochemical profile of 135 random sample obese children who attended to the Paediatric Clinic of Hamad Medical Centre (HGH) in Doha (Qatar) from January 2018 to December 2019. RESULTS: A large proportion of children presented with obesity, around the age of 5 years, were obese at the end of their first year of life (63.8%) and more were obese at the 2 years of age (82.6%). Significantly rapid gain in weight and linear growth occurred during the first 6 months of postnatal life. Moreover, some metabolic risk factors and high AIP occurred more frequently in older obese children compared to young obese children. CONCLUSIONS: This study documented the early occurrence of different components of the MetS in young obese children and the progressive increase of their prevalence in older prepubertal children. Most of obese children who presented at or below 5 years of age had significant obesity and rapid linear growth during the first two years (infancy). These two findings pointed out to the necessity to impose early detection and preventive measures on a national scale.

A Short Review on Growth and Endocrine Long-term Complications in Children and Adolescents with ß-Thalassemia Major: Conventional Treatment versus Hematopoietic Stem Cell Transplantation.

The conventional treatment of ß-thalassemia (ß-TM) patients is based on the correction of anemia through regular blood transfusions and iron chelation therapy. However, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only currently available technique that has curative potential. Variable frequency and severity of long-term growth and endocrine changes after conventional treatment as well as after HSCT have been reported by different centers. The goal of this mini-review is to summarize and update knowledge about long-term growth and endocrine changes after HSCT in patients with ß-TM in comparison to those occurring in ß-TM patients on conventional treatment. Regular surveillance, early diagnosis, treatment, and follow-up in a multi-disciplinary specialized setting are suggested to optimize the patient's quality of life (www.actabiomedica.it).

Trend in the incidence of type 1 diabetes (T1DM) among Qatari and Arab gulf children and adolescents over the past 20 years.

Letter to Editor.

Review Nutritional interventions during adolescence and their possible effects.

Nutrition is one of the most important factors affecting pubertal development. Increasing demands for energy proteins and micronutrients are necessary to cope with the rapid linear pubertal growth and development, change in body composition, and increased physical activity. Adequate nutrition is a key permissive factor for the normal timing and tempo of pubertal development. Severe primary or secondary malnutrition also can adversely delay the onset and progression of puberty. The higher incidence of anorexia nervosa and bulimia in adolescents imposes a nutritional risk on pubertal development. Here we provide an overview of nutritional requirements (macronutrients and micronutrients) necessary to cope with these changes. In addition, we discuss possible nutritional interventions trials and their effects on several aspects of growth and development in undernourished and stunted adolescents, in low- and middle-income countries (LMIC), who require nutritional rehabilitation. This mini-review sums up some important findings in this important complex that links between nutrition, nutritional interventions, and pubertal development.

Clinical and metabolic characteristics of children with hybrid diabetes mellitus (HD) compared to children with type 2 diabetes mellitus (T2DM): A preliminary comparative study.

BACKGROUND: The term double diabetes or "Hybrid Diabetes (HD)" describes diabetes with combined features of type 1 and type 2 diabetes (T2DM). PATIENTS AND METHODS: We report the clinical and biochemical characteristics of 7 children with HD and the course of their disease including the response to treatment. The data were compared to 59 children with a diagnosis of T2DM. Variables examined included age, height, weight, body mass index (BMI), triglycerides (Tg), high-density lipoprotein (HDL), and blood pressure. The Weiss criteria were used to diagnose metabolic syndrome (MetS). The atherogenic index of plasma (AIP) was calculated from the standard lipid profile. Four autoantibodies against pancreatic ß-cell were measured in all patients. RESULTS: Significant clinical and biochemical differences were detected among children with HD versus T2DM. The mean BMI of children with T2DM was significantly higher than for the HD group. At presentation, the mean C peptide level was significantly lower in HD versus T2DM group and 28% presented with diabetic ketoacidosis (DKA). The percentage of those with full criteria of MetS was significantly higher in T2DM versus HD group as well as the percentage of children with high atherogenic index. After a mean duration of 2.3 months from diagnosis, 4/7 of HD patients stopped insulin therapy and 3 patients had a marked reduction in the insulin requirement. During the follow-up (after 15 ±5 months), 5/7 HD patients required an increase in their insulin dose, one was controlled on a markedly low dose of basal insulin and the last patient did not require any insulin therapy for 40 months. CONCLUSION: Appropriate assessment of HD is necessary for early and correct diagnosis. Increasing awareness of HD among the general population and primary care practitioners is necessary for successfully and properly treating this complex disease.

A rare case of Ovarian Juvenile Granulosa Cell Tumor in an Infant with Isosexual Pseudo Puberty and a Revision of Literature.

Juvenile ovarian granulosa cell tumors (JGCTs) are described infrequently in pediatrics, and their finding in infants is exceptional. We highlight the presenting symptoms, radiologic images, operative management, and histopathologic findings of a 9-month-old female with isosexual pseudopuberty. An updated revision of literature in infants below the age of 12 months is also reported.

Incidence of type 1 and type 2 diabetes, between 2012-2016, among children and adolescents in Qatar.

INTRODUCTION: Diagnoses of type 1 DM (T1DM) and type 2 diabetes mellitus (T2DM) in youths present a substantial clinical and public health burden. The aim of this study was to determine the incidence and trend of T1DM and T2DM, among children aged 0-14 years, in Qatar. METHODS: This prospective cohort study was performed to ascertain all new cases of T1DM and T2DM 2 in Qatar as per the registry of the National Paediatric Diabetes Centre (the only tertiary care center treating children with DM in Qatar. Age-standardized and age-specific annual incidence rates for age groups 0.5-14 years were calculated. RESULTS: A total of 440 youths with T1DM (0.5 to 14 years of age) and 45 with T2DM (5 to 14 years of age) were identified in Qatar. The inclusive unadjusted estimated incidence rates of T1DM in this population over the period between 2012-2016 was 28.39/100,000 with a 95% CI of 31.82-40.03. This was significantly higher compared to the unadjusted estimated incidence registered between 2006-2011 (23.15/100,000). No case of T2DM were registered before 2008. In the following years the incidence of T2DM increased from 1.82 per 100,000 in 2012 to 2.7 per 100,000 in 2016, with an incidence of T2DM equal to 2.9/100,000 per year. CONCLUSIONS: A relatively higher incidence of T1DM compared to incidence reported worldwide have been documented in Qatar. The incidence rate increased in the period 2012-2016 compared to 2006-2011. Further studies are required to determine the causes of these increases.

Translating the HbA1c assay into estimated average glucose values in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: The A1c assay, expressed as the percent of hemoglobin that is glycated, measures chronic glycemia and is widely used to judge the adequacy of diabetes treatment and adjust therapy. Day-to-day management is guided by self-monitoring of capillary glucose concentrations (milligrams per decilitre or millimoles per litter) as well as by using continuous glucose monitoring systems (CGMS). We found a mathematical relationship between A1c and average glucose (AG) levels measured by CGMS over 5 days and determined the correlation between the variable CGMS parameters and HbA1c in 50 children with type 1 diabetes mellitus (DM-1) on MDI therapy. RESEARCH DESIGN AND METHODS: A total of 50 diabetic children randomly selected from a cohort of children with DM-1 were included in the analyses. A1c levels obtained at the end of 3 months and measured in a central laboratory were compared with the AG levels during the previous 5 days recorded by CGMS. AG was calculated by combining weighted results from 5 days of continuous glucose monitoring performed before measuring HbA1c, with 3-5 point daily self-monitoring of capillary (fingerstick) glucose. RESULTS: Linear regression analysis between the A1c and AG values provided the tightest correlations HbA1c=0.0494 MG- 2E-14, R2=0.90, P<0.0001), allowing calculation of an estimated average glucose (eAG) for A1c values. CONCLUSIONS: Our study showed a linear relationship between HbA1C and AG values measured by CGMS for 5 days before HbA1c measurement. The AG can be easily calculated using a formula derived from linear regression analysis of HbA1c data obtained in our diabetic children.

Clinical and biochemical characteristics of familial type 1 diabetes mellitus (FT1DM) compared to non-familial type 1 DM (NFT1DM).

INTRODUCTION: Familial type 1 diabetes mellitus (FT1DM) comprises parent-offspring and sib-pair subgroups. The clinical and genetic characteristics of FT1DM cases with and without affected family members have been previously studied with varying results. Some investigators found similarity of presenting features whereas others reported significant differences between the two groups. OBJECTIVE: To describe the clinical and biochemical characteristics of children with FT1DM in comparison with those with non-familial type 1 diabetes mellitus (NFT1DM). PATIENTS AND METHODS: We performed a cross-sectional retrospective study in a cohort of children and adolescents with T1DM (n=424) aged between 6 months - 16 years attending to Hamad General Hospital Pediatric Diabetes Center, Doha (Qatar) from 2012-2016. They were divided into 2 groups. Group 1 consisted of 62 children and adolescent with FT1DM (parent-offspring or sib-pair). The other group (Group 2) consisted of 431 children and adolescents with NFT1DM. The clinical presentation and prevalence of ß-cell autoimmunity (anti-glutamic acid decarboxylase (GAD) antibodies , anti-islet cell and anti-insulin antibodies), thyroid function (Free thyroxine: FT4 and thyroid-stimulating hormone: TSH), anti-thyroid peroxidase antibody (TPO) and anti-tissue transglutaminase (ATT) at their first presentation were recorded, described and analyzed. RESULTS: FT1 DM was more prevalent in boys versus girls (1.4:1, respectively) whereas the prevalence of NFT1DM did not differ between genders (1:1.1, respectively). F1DM occurred relatively early in childhood (40.7% before the age of 4 years and 72% before 9 years of age) versus NFT1DM which occurred relatively later in life (80% after the age of 4 years and 40% after the age of 9 years). 35.2% of FT1DM presented with diabetic ketoacidosis (DKA) versus 32.5% of T1DM patients. Anti-islet antibodies (Ab) were detected more frequently in FT1DM versus NFT1DM. The prevalence of positive anti-insulin and anti- GAD antibodies did not differ between the two groups. Anti TPO were detected in 27.2% of NFT1DM and 35.5% of FT1DM. A primary hypothyroidism, with positive ATPO, was more prevalent in FT1DM versus NFT1DM. ATT IgA was high in 5% of NFT1DM and 19.8% of FT1DM whereas ATT IgG was high in 4.4 % of NFT1DM and 15.4% of FT1DM. CONCLUSIONS: FT1DM is more prevalent in boys versus girls and occurs earlier in childhood compared to NFT1DM. Primary hypothyroidism was more prevalent in NFT1DM versus FT1DM. Anti-islet Ab and ATT antibodies were more prevalent in the FT1DM versus NFT1DM. The genetic background may explain some differences between FT1DM and NFT1DM including the age of onset, gender affection, as well as associated autoimmune disorders.

Prevalence of ß-cell antibodies and associated autoimmune diseases in children and adolescents with type 1 diabetes (T1DM) versus type 2 diabetes (T2DM) in Qatar.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is an autoimmune disease with the development of abnormal immune responses to specific ß-cell autoantigens in addition to other organ-specific autoimmunity. The most frequent associated disorders are thyroid dysfunctions and celiac disease. There are limited studies in the current literature on the prevalence of associated autoimmunity, especially multiple, in children and adolescents with T1DM and Type 2 diabetes mellitus (T2DM). OBJECTIVES: The aim of the present study was to determine the prevalence of autoantibodies and thyroid dysfunctions in a cohort of children and adolescents (aged 0.5-16 years) with T1DM living in Qatar. RESEARCH DESIGN AND METHODS: The records of all children and adolescents attending the Pediatric Diabetes Center of Hamad Medical Center, for the past 5 years (from January 2012 to December 2016), were reviewed and all clinical and biochemical data, including ß-cell autoimmunity [anti-glutamic acid decarboxylase (GAD) antibodies, anti-islet cell and anti-insulin antibodies (IAA)], thyroid function (Free thyroxine: FT4 and thyroid-stimulating hormone: TSH), anti-thyroid peroxidase antibodies (TPO) and anti-tissue transglutaminase (ATT) were collected at their first presentation (cross-sectional study). Data for patients with T1DM (n=431) and T2DM (n=59) were recorded analyzed and the prevalence calculated and compared with other studies. RESULTS: The prevalence of anti-GAD antibodies was 75.5 % in T1DM and 29.3% in T2DM. Anti ß-islet antibodies (Ab) were detected in 53.4% of T1DM and 29.4% of T2DM. Anti-insulin Ab were detected in 40.4% of T1DM and 58.3% of T2DM. The three antibodies together were detected in 18.4 % of T1DM and none of T2DM. At presentation, hypothyroidism (FT4 <11.5 pmol/L) was detected in 10.6% of T1DM and 10% of T2DM.  Subclinical hypothyroidism was diagnosed in 3.5% of T1DM and 8% of T2DM. High anti TPO was detected in 27.2% of T1DM and 34.6% of T2DM. High TPO with normal thyroid function were found in 22.7% of T1DM and 23.1% of T2DM. ATT IgA was high in 5% of T1DM and 8.7% of T2DM whereas ATT IgG was high in 4.4 % of T1DM and not detected in any patient with T2DM. Mucosal biopsy proved celiac disease in 9 out of 12 patients (75%) with positive ATT IgA and IgG antibodies. CONCLUSIONS: Qatar has a relatively high incidence of T1DM compared to incidences reported worldwide. The incidence increased over the period 2012-2015.  We report a high prevalence of associated autoimmune abnormalities in our patients with T1DM and T2DM. These data strengthen the argument for routine screening of all children and adolescents with T1DM and T2DM for other autoimmune disorders, particularly the thyroid gland.