The spectrum of clinical, hormonal findings in children with congenital adrenal hyperplasia in Isfahan province; a 20-year review.

OBJECTIVES: Congenital adrenal hyperplasia is an autosomal recessive disorder caused by complete or partial defects in one of the several steroidogenic enzymes involved in synthesizing of cortisol from cholesterol in the adrenal gland. Prompt and proper treatment of the disease would reduce symptoms and the level of androgens in patients. The present study aimed to evaluate the demographic characteristics and clinical findings of these patients. METHODS: This retrospective investigation was conducted in 146 patients with congenital adrenal hyperplasia participated. Their clinical and paraclinical findings were accurately recorded in the file and extracted from the records. RESULTS: Among all 146 patients, 119(81.5 %) was 21-OH Deficiency type;11-OH Deficiency type was 13(8.9 %), 10(6.8 %) was 3ß-HSD type, StAR was 2(1.4 %) and 17 alpha(α)-hydroxylase Deficiency was 2(1.4 %). The mean age of disease onset in these patients was 2.45 ± 1.16 years. Macropenis was the most frequent clinical finding in 39 cases of 64 boys (60.9 %), and Clitoromgaly was the most clinical presentation in 40 cases of 82 girls (48.7 %). The levels of testosterone, dehydroepiandrosterone sulfate, and 17-OHP significantly decreased in the last visit compared to the initial diagnosis. CONCLUSIONS: Based on the clinical findings in every infant or child with ambiguous genitalia, macropenis, clitoromegaly, hirsutism, and premature pubarche, we should consider congenital adrenal hyperplasia. Prompt and proper treatment and disease control would reduce symptoms and the level of androgens in patients.

The longitudinal growth trajectory of children with congenital hypothyroidism during the first 3 years of life.

Congenital hypothyroidism (CH) is detected through a newborn screening program in Iran, enabling early detection and prompt treatment. This study addresses the longitudinal growth trajectory of Iranian children with CH and explores associated factors during the first 3 years of life. Data from 1474 children with CH in Isfahan, Iran (2002-2022), were analyzed. Weight, height, and head circumference were measured, and z-scores for age were calculated. Group-based trajectory modeling was applied to distinct growth trajectories. Factors influencing growth patterns, including gender, treatment initiation age, delivery method, parental consanguinity, history of familial hypothyroidism, and thyroid-stimulating hormone (TSH) levels at 3-7 days, were investigated. Thirty-seven percent of children diagnosed with CH faced a delay in weight, while 36.6% experienced stunted height, and 25.7% showed a retardation in head circumference growth. The initiation of treatment, parental consanguinity, and family history of hypothyroidism varied among these groups. Children exhibiting an optimal growth pattern in the initial 3 years of life demonstrated lower average TSH levels. CONCLUSION: This research emphasizes the complexity of managing CH and stresses the importance of tailoring interventions based on individualized characteristics and the ongoing growth patterns of the children. Future research is required to understand the intricate relationships between growth patterns and various determinants and optimize the growth and developmental outcomes of children with CH. WHAT IS KNOWN: • Iran has a higher prevalence of congenital hypothyroidism (CH) with a nationwide screening program. • There are concerns about delayed growth in CH children, but limited research on long-term patterns and contributing factors. WHAT IS NEW: • Distinct patterns in weight, height, and head circumference among children with CH were identified. • Factors such as consanguinity, parental hypothyroidism, and TSH levels impact growth outcomes. • CH management is complicated, and there is a need for individualized interventions.

Association Between Dietary Phytochemical Index and Neonatal Thyroid Function.

Background: Thyroid hormones regulate fetal growth and differentiation of several tissues. Maternal dietary patterns may be correlated with changes in the level of neonatal thyroid-stimulating hormone (TSH). We hypothesized that since maternal nutrition affects birth weight and offspring growth, it may also impact endocrine patterns in offspring. This study is aimed at assessing the relationship between maternal dietary phytochemical index (DPI) in the first trimester of pregnancy and neonatal cord blood thyroid hormone levels. Methods: This cross-sectional study is a substudy of a birth cohort. Overall, 216 mothers, aged 16-45 years, were recruited in their first trimester of pregnancy. To calculate DPI, the daily energy percentage of phytochemical-rich foods was divided by the total daily energy intake. At delivery time, TSH and free thyroxine (FT4) levels were measured in cord blood samples using chemiluminescence immunoassay. Results: The mean (standard deviation (SD)) age of mothers was 29.56 (5.50) years, and 47% of newborns were girls. The mean (SD) of DPI in the first, second, third, and fourth quartiles was 25.03 ± 4.67, 33.87 ± 2.18, 40.64 ± 2.10, and 51.17 ± 4.98, respectively. There was not any significant correlation between DPI score with cord serum TSH and FT4 levels in crude and adjusted analysis. Conclusion: No significant relationship between maternal DPI with cord serum TSH and FT4 levels was shown. Limited experience exists about the effect of maternal diet quality indices on neonatal thyroid function, and further studies are needed in this regard.

First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults.

This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.

Evaluation of the safety and efficacy of biosimilar recombinant growth hormone in children with growth hormone deficiency: non-inferiority, randomized, parallel, multicentric and Phase III trial.

OBJECTIVES: This study is designed in order to compare the efficacy and safety of recombinant human growth hormone (rhGH) with the reference brand. METHODS: According to the inclusion criteria, 85 people in 13 Iranian centers were randomly selected to receive biosimilar Somatropin (Somatin®) (44 people) and reference Somatropin (Norditropin®) (41 people) at a dose of 35 µg/kg/d, seven days/week for 12 months. The primary outcomes included height velocity (HV) was measured during 12 months of treatment. RESULTS: The two intervention groups' Height changes were similar. The mean HV was 10.96 cm/year in the biosimilar group and 10.05 cm/year in the reference groups after 12 months. Estimates of the lower bounds of 95% CI for mean height differences in the biosimilar intervention group compared to the reference intervention group did not exceed the 2 cm margin. Therefore, the non-inferiority of biosimilar intervention compared to the brand product is verified. Common ADRs in both groups were nausea in two patients (2.4%), diarrhea in two patients (2.4%), increased body temperature in one patient (1.2%), and headache in one patient (1.2%). CONCLUSIONS: The finding of this study indicated that Somatin® and Norditropin® have comparable efficacy and safety profiles. CLINICAL TRIAL REGISTRATION: www.IRCT.irIRCT20171122037571N1.

Association between maternal and cord blood thyroid hormones, and urine iodine concentration with fetal growth.

OBJECTIVES: We planned to evaluate the association of fetal and maternal thyroid hormones and maternal iodine status with neonates' anthropometric parameters. METHODS: In this cross-sectional study, levels of thyrotropin were measured in maternal serum in the first trimester of pregnancy, and thyrotropin (TSH) and free thyroxin (fT4) were measured in cord blood serum samples at birth. Urinary iodine concentration (UIC) levels in random urine samples of mothers were measured in the third trimester of pregnancy. The relationship between UIC and thyroid hormone levels of mothers with neonates' anthropometric birth parameters of neonates was evaluated. RESULTS: One hundred eighty-eight mother-newborn pairs completed the study. Mean (SD) of cord blood TSH (CB-TSH), cord blood-free thyroxin (CB-FT4) values, and maternal TSH (M-TSH) levels were 8.8 (7.3) mIU/L, 1.01 (0.2) ng/dL, and 2.2 (0.9) mIU/L, respectively. After adjusting for confounders, there was a positive significant association between female neonate length and maternal TSH and log log-transformed CB TSH (LN_CB-TSH) (p<0.05). Median UIC (Q1-Q3) was 157 (53-241) µg/L, and there was no association between birth weight, birth length, and head circumferences of neonates and mothers' UIC (p>0.05). CONCLUSIONS: We found a positive correlation between maternal TSH in the first trimester of pregnancy and the birth length of newborns, and a negative correlation was observed between CB-TSH and birth length in girls, but it did not provide conclusive evidence for the relationship between maternal and neonatal thyroid hormone levels and birth weight. There was no association between maternal UIC levels in the third trimester and birth anthropometric parameters.

Quality of Life in Patients with Phenylketonuria: A Systematic Review.

The impact of phenylketonuria (PKU) on Quality of life (QoL) has been a topic of interest in recent research. This article reviews current researches on the impact of PKU on QoL. The review examines factors that may influence QoL, such as age, metabolic control, and treatment adherence. In this systematic review study, relevant articles were identified using a search strategy built with the keywords phenylketonuria, PKU, or hyperphenylalaninemia (or their synonyms) and QoL in Web of Science, Scopus, and PubMed databases. After identifying the articles, duplicates, reviews, scientific abstracts, articles published in languages other than English, and non relevant studies were excluded. The search strategy identified 951 records from databases, and after excluding duplicates, irrelevant studies, and those published in non English languages, 26 records were left that contained data on 1816 patients with PKU/hyperphenylalaninemia. The studies included both children/adolescents and adults. Overall, the studies found that the QoL of PKU patients was comparable to normative data, but some aspects such as emotional health and school functioning were lower. Metabolic control was found to significantly correlate with QoL. Younger patients and men had better QoL in several studies, while late treated patients and those with lower education had worse outcomes. It is concluded that QOL in patients with PKU is similar to the general population. However, given the chronic nature of the condition, it is important to pay special attention to their QoL. Poor QOL is associated with female gender, lower education, older age, and poor metabolic control.

Visual Perception in Children with a History of Hypoglycemia due to Hyperinsulinism.

Objectives: Hyperinsulinism refers to improper insulin secretion in the presence of low plasma glucose, causing severe and persistent hypoglycemia in infants and children. The brain's occipital lobe, which includes the visual and plays an essential role in visual perception is specifically sensitive to hypoglycemia-induced damage. The present study aims to investigate the visual perception in children suffering from hyperinsulinism and to compare it with the control group. Materials & Methods: This cross-sectional control study, conducted in 2020 in Isfahan, Iran, involved 20 children aged 4-13 years with hyperinsulinism and 20 healthy children of the same age and gender for comparison. In both groups, the measuring instrument was the Test of Visual Perceptual Skills (non-motor) Third Edition. Results: The mean visual perceptual quotient in the case and control groups was 80.50±26.74 and 116.50±7.56 (p-value<0.001), respectively. The results overall indicated that children suffering from hyperinsulinism were weaker than healthy children in all areas of visual perception. Conclusion: Based on the obtained results, it is recommended that children suffering from hyperinsulinism be screened regarding visual perceptual disorders since this screening may be helpful in initiating different rehabilitation programs among these patients.

Validity and reliability of parent assessments of pubertal maturation among adolescent girls in Isfahan, Iran.

OBJECTIVES: The current paper presents the steps considered for validation of a questionnaire for assessment of sexual maturity among Iranian adolescent girls. METHODS: This cross-sectional study was performed in 2022 in Isfahan, Iran. Based on the Growth and Development Questionnaire that included both the Pubertal Development Scale (PDS) and Sexual Maturation Scale (SMS), two Persian questionnaires were prepared. The face validity, content validity, criterion validity, and reliability of the questionnaire were assessed. We compared agreement of two parent-reported measures of puberty, SMS and PDS, with clinical Tanner stages (TSs) as the gold standard. Percent agreement, Cohen's kappa coefficient, and Kendall's τ b were used to assess the agreement between maternal assessments with clinical TS. The intraclass correlation coefficient (ICC) and the Cronbach's α coefficient were also calculated to evaluate the reliability of the questionnaire. RESULTS: A total of 150 students aged 6-17 years with mean (SD) age of 10 (2.04) completed this study. The percentages of agreement for the mother-reported SMS in relation to clinical TS for breast stage and pubic hair stage were 60 % and 53.8 %, respectively. The percentages of agreement of the mother-reported PDS in relation to clinical TS for breast stage and pubic hair stage were 55.8 and 66 %, respectively. The weighted kappa coefficients showed moderate agreement, with weighted kappa ranging from 0.52 to 0.61. The mother-reported SMS and PDS showed high reliability. The Cronbach's alpha of the PDS and the SMS was 0.88 and 0.83, respectively. The ICC of the mother-reported SMS and the mother-reported PDS was 0.95 (0.92-0.98) and 0.97 (0.94-0.98), respectively. CONCLUSIONS: This study indicated that a maternal assessment of sexual maturity using the PDS or SMS can reliably estimate pubertal development in adolescent girls in an Iranian population.

Final height in children and adolescents with type 1 diabetes mellitus: A systematic review and meta-analysis.

PURPOSE: Considering the high prevalence of type 1 diabetes mellitus (T1DM) together with the importance of improved physical growth and the significance of promoting healthcare quality among T1DM children, this meta-analysis aims to determine mean final height in this population group. METHODS: We systematically searched PubMed, EMBASE, Web of Science, Scopus, and Cochrane databases for all studies published until May 2023 and reviewed references of published articles. Meta-analytic procedures were used to estimate the effect size (mean final height Z-score) among T1DM children in a random effects model. Significance values, weighted effect sizes, 95% CIs, and tests of homogeneity of variance were calculated. The included studies consisted of data from 3274 patients. RESULTS: The mean final height Z-score for T1DM children was -0.201 (n = 25 studies, 95% CI: -0.389, -0.013; I2 = 97%), -0.262 in males (n = 20 studies, 95% CI: -0.539, 0.015, I2 = 97.1%), and -0.218 in females (n = 18 studies, 95% CI: -0.436, 0, I2 = 94.2%). The non-significant negative association between age at diagnosis, HbA1c levels, and final height Z-score is suggested by the findings of the univariate meta-regression. CONCLUSION: Our findings indicated that children with T1DM have impaired linear growth and that monitoring of growth in these patient populations is an important issue in the management of T1DM. Due to a scarcity of studies providing data on the relationship between uncontrolled diabetes (increased HbA1c) and early diagnosis and final height, further investigation is warranted to determine whether there is indeed a correlation. Consequently, any conclusion regarding the association between uncontrolled diabetes (elevated HbA1c), early diagnosis of T1DM, and the increased risk of impaired linear growth or final height remains uncertain.

Evaluation of cardiac findings in mucopolysaccharidosis.

PURPOSE: Mucopolysaccharidoses (MPS) are a group of rare genetic diseases and heart involvement is one of the important conflicts in most types, which may cause serious complications. We used M-Mode and two-dimensional speckle tracking echocardiography (2D-STE) to explore cardiovascular involvements in MPS patients. METHOD: The present cross-sectional study investigated the frequency of cardiac involvements in MPS patients. Included participants were MPS types I, II, III, IV, and VI who underwent specialized echocardiography exams to assess valvular function, systolic and diastolic function, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). RESULTS: 35 patients were enrolled in this study. The total mean age of patients was 9.58 ± 5.11 years and 71.4% were male. Type IV (40%) and type III (31.4%) were the most frequent MPS. Although LVEF did not differ notably among MPS types, GLS was significantly different (p = 0.029). Mitral regurgitation was observed remarkably more in MPS type III (p = 0.001) while mitral stenosis was more common in type III (p = 0.007). There was a significant association between LVEF and GLS (ß= -0.662; p = 0.025) and between LVEF and MPS type (ß = 1.82; p = 0.025) when adjusted for GLS. CONCLUSION: Cardiac complications are very common and are one of the most important causes of death in MPS patients. 2D-STE seems to be superior to M-Mode for detection of early and subclinical cardiac dysfunction in MPS patients.

Relationship between vitamin D levels and age of menopause and reproductive lifespan: Analysis based on the National health and nutrition examination survey (NHANES) 2001-2018.

OBJECTIVES: To determine the association between serum vitamin D levels and age at menopause and reproductive lifespan in a group of US postmenopausal women. STUDY DESIGN: Data from 6,326 postmenopausal US women in the National Health and Nutrition Examination Survey (NHANES) database 2001-2018 were obtained. Weighted multinomial logistic regression models were used to obtain odds ratios (OR) and 95% confidence intervals (CI). Statistical analyzes were performed using SAS (version 9.4; SAS Institute), and complex survey designs were considered. RESULTS: Vitamin D deficiency was associated with a higher likelihood of early menopause (OR = 1.34, 95% CI: 1.15, 1.58; p = 0.008) and lower odds of late menopause (OR = 0.79, 95% CI: 0.52, 0.95) in the unadjusted model but not in the adjusted model. Lower vitamin D levels were associated with a higher risk of a shorter reproductive lifespan. The strongest association was seen in the first tertile of vitamin D deficiency (OR = 1.54; 95% CI: 1:29-1:83). After adjustment, the associations were somewhat weakened but remained statistically significant. CONCLUSIONS: The results of this study suggest that vitamin D deficiency and inadequacy might be associated with earlier age at menopause. It may also reduce the reproductive lifespan in women. Given the cross-sectional nature of the NHANES dataset, these results should be interpreted with caution due to temporality bias. Menopausal age is a multifactorial phenomenon, and the identification of factors and their interactions should be evaluated in future studies.

Association of Polycyclic Aromatic Hydrocarbons Urine Metabolites with Type 1 Diabetes.

Purpose: Polycyclic aromatic hydrocarbons (PAHs) are believed to be a possible factor in the development of cancer, ischemic heart disease, obesity, and cardiovascular disease. The objective of this study was to explore the association between certain metabolites of urinary PAH and type 1 diabetes (T1D). Methods: In Isfahan City, a case-control study was carried out involving 147 T1D patients and an equal number of healthy individuals. The study measured the levels of urinary metabolites of PAHs, specifically 1-hydroxynaphthalene, 2-hydroxynaphthalene, and 9-hydroxyphenanthrene, in both the case and control groups. The levels of these metabolites were then compared between the two groups to assess any potential association between the biomarkers and T1D. Results: The mean (SD) age of participants in the case and control groups was 8.4 (3.7) and 8.6 (3.7) years old, respectively, (P > 0.05). In terms of gender distribution, 49.7% and 46% of participants in the case and control groups were girls, respectively (P > 0.05). Geometric mean (95% CI) concentrations were: 36.3 (31.4-42) µg/g creatinine for 1-hydroxynaphthalene, 29.4 (25.6-33.8) µg/g creatinine for 2-hydroxynaphthalene, and 72.26 (63.3-82.5) µg/g creatinine for NAP metabolites. After controlling for variables such as the child's age, gender, maternal and paternal education, duration of breastfeeding, exposure to household passive smoking, formula feeding, cow's milk consumption, body mass index (BMI), and five dietary patterns, it was observed that individuals in the highest quartile of 2-hydroxynaphthalene and NAP metabolites had a significantly greater odd ratio for diabetes compared to those in the lowest quartile (P < 0.05). Conclusion: Based on the findings of this study, it is suggested that exposure to PAH might be linked to an increased risk of T1D in children and adolescents. To clarify a potential causal relationship related to these findings, further prospective studies are needed.

New molecular insights into the A218V variant impact on the steroidogenic acute regulatory protein (STAR) associated with 46, XY disorders of sexual development.

Disorders of sexual development (DSD) are an abnormal congenital conditions associated with atypical development of the urogenital tract and external genital structures. The steroidogenic acute regulatory (STAR) gene, associated with congenital lipoid adrenal hyperplasia (CLAH), is included in the targeted gene panel for the DSD diagnosis. Therefore, the genetic alterations of the STAR gene and their molecular effect were examined in the CLAH patients affected with DSD. Ten different Iranian families including twelve male pseudo-hermaphroditism patients with CLAH phenotype were studied using genetic linkage screening and STAR gene sequencing in the linked families to the STAR locus. Furthermore, the structural, dynamical, and functional impacts of the variants on the STAR in silico were analyzed. Sanger sequencing showed the pathogenic variant p.A218V in STAR gene, as the first report in Iranian population. Moreover, modeling and simulation analysis were performed using tools such as radius of gyration, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and molecular docking showed that p.A218V variant affects the residues interaction in cholesterol-binding site and the proper folding of STAR through increasing H-bound and the amount of α-Helix, deceasing total flexibility and changing fluctuations in some residues, resulting in reduced steroidogenic activity of the STAR protein. The study characterized the structural and functional changes of STAR caused by pathogenic variant p.A218V. It leads to limited cholesterol-binding activity of STAR, ultimately leading to the CLAH disease. Molecular dynamics simulation of STAR variants could help explain different clinical manifestations of CLAH disease.

The Consensus on the Diagnosis and Management of Congenital Hypothyroidism in Term Neonates.

Congenital hypothyroidism (CH) is one of the most treatable endocrine disorders in infants and children that can influence the function of many organs in the body. On-time diagnosis and treatment can prevent the adverse effects of thyroid hormone deficiency on the child's neurodevelopment. There are many challenges in screening, post-screening, diagnosis, and managing this disorder. Therefore, this article aimed to mention updated information on this issue. Although there are different approaches for the treatment of hypothyroidism, the authors decided to create a national approach based on the conditions of our country.

Trends in incidence rates of childhood type 1 diabetes mellitus: A retrospective study in Isfahan province, Iran.

AIMS/INTRODUCTION: We aimed to determine the incidence trend of childhood type 1 diabetes mellitus in Isfahan province over a period of 12 years. MATERIALS AND METHODS: In this retrospective study, children aged <20 years at the time of type 1 diabetes mellitus diagnosis, from March 2007 to March 2019, were included. The crude and adjusted incidence rate of type 1 diabetes mellitus is calculated as the number of cases per 100,000 person-years by the period. The cumulative, age- and sex-specific incidence rates were also calculated. Age-specific incidence rates were calculated for age and sex groups. RESULTS: A total of 1,954 (983 boys and 971 girls) cases of type 1 diabetes mellitus were identified. The mean age at diagnosis in all studied populations was 9.89 (standard deviation 4.76). There were no significant differences between the proportion of boys and girls in different years (P = 0.12) and different age groups (P = 0.19). The average annual percent change of incidence rate for the total population, for girls and boys, was 6.9%, 6.7% and 6.3% respectively. The type 1 diabetes mellitus incidence rate had a significant trend to be increased from 2007 to 2019 (P < 0.001, t = 3.6). CONCLUSION: Our findings showed that currently our region is considered a region with a high incidence rate of type 1 diabetes mellitus. Although we have had fluctuations in the incidence rate over the 12 years, the overall trend is increasing.

A Novel Homozygous Pathogenic Variant in CYP11B1 in a Female Iranian Patient with 11B Hydroxylase Deficiency.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) addresses a number of autosomal recessive disorders characterized by the enzyme defects in steroid hormones biosynthesis. The second common form of CAH is caused by mutations in the CYP11B1 gene. Here, we reveal a novel mutation in the CYP11B1 gene related to the 11ßOHD phenotype. METHODS AND RESULTS: Sequence analysis of the CYP11B1 gene in a 19-year-old Iranian woman with the 11ßOHD phenotype was performed. In silico analysis and molecular docking were done. A novel missense homozygous variant c.1351C > T (p.L451F) in the CYP11B1 gene was identified in the patient and, according to American College of Medical Genetics and Genomics criteria, was categorized as likely pathogenic. Protein docking showed destructive effects of the variant on the CYP11B1 protein-ligand interactions. CONCLUSION: This study broadens the CYP11B1 mutation spectrum and introduces the novel p.L451F likely pathogenic variant leading to destructive effects on protein-ligand interactions. Our results provide reliable information for genetic counseling and molecular diagnostics of CAH.

Association between Sleep Duration and Early Pubertal Timing in Children and Adolescents: A Systematic Review and Meta-analysis.

BACKGROUND: Early puberty increases the risk of diverse health outcomes during adolescence and beyond. Several studies have explored the links between short sleep duration and early puberty worldwide. OBJECTIVE: The current systematic review and meta-analysis aimed to evaluate the association between sleep duration and early pubertal timing based on published evidence systematically. METHODS: We searched important electronic databases for articles that reported the association between childhood sleep duration and puberty timing up to October 2020. A total of 848 papers were identified from the databases and manual search. Finally, 10 studies including 23752 participants were included in the meta-analysis. We calculated the pooled effect sizes using a random or fixed effects model as appropriate. RESULTS: There was a significant inverse association between sleep duration and the risk of early puberty, longer duration of sleep was associated with 0.34% decreased odds of early puberty (OR = 0.66, 95% CI = 0.58-0.77, I2 = 96.6%). In a subgroup analysis, when pubertal status was assessed by physical examination compared with Pubertal Development Scale (PDS) or Sexual Maturation Scale (SMS), the associations between sleep duration and age of puberty were attenuated. The pooled OR (95% CI) of studies measuring pubertal timing by PDS/SMS and Tanner stage were 0.50(0.37-0.69) and 0.91(0.77-1.09), respectively. When pooling effect sizes was limited to studies that had BMI level adjustment, the association of sleep duration and early puberty was not statistically significant anymore (OR = 0.95, 95% CI = 0.89-1.01). CONCLUSION: Longer sleep duration is associated with a lower risk of early puberty in children. The association between sleep duration and risk of early puberty may be modified by other factors such as BMI. To clarify the effect of sleep duration on the risk of early puberty in children, further prospective studies are needed.

Evaluation of Growth Hormone Deficiency in Children with Cystic Fibrosis.

Background: Due to chronic respiratory and gastrointestinal problems, growth failure is a common issue in patients with cystic fibrosis (CF). The present study aimed to investigate the prevalence of growth hormone deficiency (GHD) in CF children with stable gastrointestinal and respiratory conditions. Materials and Methods: In this study, the growth indicators of all 4-16-year-old children referred to two CF clinics were monitored over 3 years. Children without severe gastrointestinal or pulmonary symptoms with weight <3% percentile or whose height increase were two standard deviations below their expected height growth over 6 months were selected for the growth hormone (GH) stimulation test by clonidine and L-dopa test. Some of the children without CF, who were also referred for height growth disorders and matched the CF group, were considered the control group. They underwent the GH stimulation test, and the results were compared. Results: From 150 patients with CF, growth failure was observed in 24 patients with stable gastrointestinal and respiratory conditions; in 10 of them, the GH stimulation test was deficient. The prevalence of GHD was 6.6% in CF patients. In the control group of 30 children without CF, but with growth failure, the GH was deficient in nine cases, implying no significant difference with the case group (P = 0.37). Conclusion: In our study, the prevalence of GHD was 6.6% in CF patients, whereas the prevalence GHD in the normal population of childhood is <1%. Therefore, further studies should be designed to investigate the cause of GHD in CF patients.

Cognitive function in untreated subjects with mild hyperphenylalaninemia: a systematic review.

BACKGROUND: This systematic review study aims to evaluate the cognitive function of patients with mild hyperphenylalaninemia (mHPA) without treatment. METHODS: A systematic literature search was done from the 1st of May to the 30th of July in 2021 on published studies. The search strategy was ((hyperphenylalaninemia) OR (phenylketonuria) AND (cognition)). We use PubMed, Scopus, and the Web of Science databases. Studies which reported their findings regarding the cognitive function of patients with mHPA (screening serum phenylalanine > 120 and < 600 µmol/L) were included and reviewed. RESULTS: From initially retrieved 2805 studies, finally, 15 studies (10 on untreated patients with Phe levels below 360 µmol/L, 7 on untreated patients with Phe levels between 360 and 600 µmol/L, four 120-600 µmol/L) were selected. Most of the studies used the Wechsler Intelligence Scale for IQ evaluation, two (2/15) of them used the Stanford-Binet test and two used both tests. Four studies have reported a worse cognitive outcome compared to the control group, and in one study, relative defects in attention and working memory were reported. Other studies have reported normal IQ levels and no significant cognitive defects. CONCLUSION: It is suggested that Phe levels between 120 and 360 µmol/L are generally safe. Some studies showed that untreated patients with higher levels might show some degrees of cognitive impairment. In conclusion, current knowledge is insufficient to state that treatment is not required for HPA patients to preserve their cognitive status, especially in patients with Phe levels of 360-600 µmol/L. Further studies with a larger sample size and standardized cognitive function evaluation tools are needed.