Fawzia Alyafei

Background: Thalassemia represents the world’s most prevalent inherited hemoglobin disorder, affecting approximately 4.4 per 10,000 live births globally. Accurate genetic characterization is indispensable both for definitive diagnosis and for lifetime clinical monitoring. The past two decades have witnessed a paradigm shift from conventional protein-based assays toward comprehensive molecular techniques, including next-generation sequencing (NGS), third-generation (long-read) sequencing, and preimplantation genetic testing for monogenic disease (PGT-M). Objectives: (1) To systematically evaluate the molecular techniques available for confirming the diagnosis of alpha- and beta-thalassemia, including their diagnostic accuracy, indications, and limitations; (2) to examine how genotype–phenotype correlation and genetic modifier profiling inform clinical prognosis and therapeutic decision-making; and (3) to define evidence-based genetic monitoring parameters for longitudinal follow-up of patients receiving transfusions, iron chelation, and novel curative therapies including gene therapy. Methods: A comprehensive narrative review was conducted by systematically searching PubMed/MEDLINE for English-language peer-reviewed articles published between January 2000 and December 2024. Forty-three studies were ultimately included after applying predefined inclusion and exclusion criteria. Quality of included studies was assessed using SANRA (Scale for the Assessment of Narrative Review Articles). Results: HPLC and capillary electrophoresis remain first-line phenotyping tools; DNA-based confirmation is mandatory for complete genotyping. NGS-based targeted panels detect >95% of common mutations but require MLPA co-testing or long-read sequencing for structural variants. Genotype–phenotype prediction is substantially enhanced by profiling three major modifier loci: XmnI (Gγ), BCL11A, and HBS1L-MYB. PGT-M using NGS achieves near-complete genotyping accuracy (>99%) with live birth rates of 40–60% per frozen embryo transfer cycle. For patients receiving curative gene therapy (exagamglogene autotemcel / Casgevy), molecular follow-up protocols spanning 15 years are now recommended. Cardiac T2* MRI remains the most reliable non-invasive tool for iron overload follow-up, superior to serum ferritin alone. Conclusion: A tiered, genotype-informed approach—combining HPLC/CE phenotyping, targeted molecular diagnostics, genetic modifier profiling, and periodic re-evaluation—optimizes diagnostic precision and guides individualized management across the thalassemia spectrum. Integration of PGT-M and long-read sequencing into standard care pathways, alongside robust gene therapy follow-up protocols, will define the next era of thalassemia genetics.

The purpose of this study is to systematically review human evidence linking placental hormones and IGF-1 with fetal growth, birth size, and early-life metabolic programming, and to identify disease-specific translational signals relevant to fetal growth restriction, metabolically complicated pregnancy, and extreme prematurity. A systematic review of PubMed and Scopus was performed for human studies published from January 2000 to March 2025. Eligible studies examined placental growth hormone, human placental lactogen, placental IGF-axis markers, or related stress-hormone pathways in relation to birth size, fetal or infant growth, or early metabolic outcomes. Reporting was aligned with PRISMA 2020. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I principles for observational studies. Because of substantial clinical and methodological heterogeneity, findings were synthesized narratively. Thirty-seven included studies showed that mid-gestation placental growth hormone had the most consistent positive associations with fetal growth and birth size, whereas early placental growth hormone was less informative. Cord blood IGF-1 was the most reproducible endocrine correlate of birth length and weight. Reduced maternal or placental lactogen signals and lower placental 11β-HSD2 activity clustered with placental insufficiency and fetal growth restriction, while diabetic pregnancies showed a shift toward adiposity-related outcomes. In extreme prematurity, abrupt loss of placental endocrine support created a translational window in which rhIGF-1/rhIGFBP-3 replacement emerged as the clearest mechanism-based intervention, although current clinical evidence remains preliminary. Conclusion: Placental endocrine markers should not be used as standalone screening tools. Their main value at present is mechanistic and translational: combined hormone patterns may refine biological understanding and risk stratification within defined maternal and neonatal disease frameworks, while IGF-1 replacement in extreme prematurity represents the most credible current therapeutic lead. What is Known: • Placental hormones and IGF-1 are linked with fetal growth, birth size, and neonatal metabolic adaptation, but 45 published evidence is heterogeneous and clinically fragmented. What is New: • This systematic review organizes the human data within fetal growth restriction, diabetic/LGA pregnancy, and extreme prematurity frameworks and identifies translational signals—especially early IGF-1 replacement in extreme prematurity—rather than standalone diagnostic biomarkers. Graphical Abstract The alternative text for this image may have been generated using AI.

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. 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. 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. Monitoring and early diagnosis of these conditions are of paramount importance for successful management.

Data about placental weight (PW) in relation to birth weight (BW) and gestational age (GA) are lacking in Arabic countries. (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. 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. 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. 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.

Patients with β-thalassemia major (BTM) had variable prevalence of undernutrition and abnormal body composition. 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. 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. Timely detection of undernutrition in patients with BTM and proper nutritional intervention could prevent growth delay and comorbidities. (www.actabiomedica.it)

Steroids are the main drugs used for the treatment of nephrotic syndrome (NS) in children. 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. 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%. 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.

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.