A Systematic Review and Meta-Analysis of Stature Growth Complications in β-thalassemia Major Patients

Abstract

Background: Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients’ anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can’t excrete excess iron from the bloodstream. Objective: To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major ( β TM) patients. Methods: We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major ( β TM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses. Findings: Seventy–four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3–62.6) and in male was higher than female (61.9%, 95% CI 53.4–69.7 vs. 50.9%, CI 41.8–59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8–84 vs. 33.1%, CI 9.4–70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16–40.8). Conclusion: Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients’ complications.

Endocrine Complications and the Effect of Compliance with Chelation Therapy in Patients with Beta Thalassemia Major in Eastern Province of Saudi Arabia

“…In this study, the prevalence of short stature (35.2%) is lower compared to data from a study performed across 16 countries and reported that 53.0% were short, with a positive association between gender and short stature ( P value< 0.006 ) showing prevalence of 61.49% in males and 38.5% in females. 13 While, the prevalence of short stature in our study was statistically significantly lower in females than in males ( P value= 0.05 ). Short stature was present in 29% of female patients based on the growth charts for Saudi children and adolescents compared to 71% of males in the study.…”

New Entity—Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement

“…The keywords of research are “beta-thalassemia” in combination with one of the following: “endocrine”, “fertility”, respective “pregnancy”; but, also, “hypogonadism”, “thyroid”, “TSH”, “parathyroid”, “parathormone”, “stature”, “puberty”, “pituitary”, “diabetes”, “glycaemia”, “fracture”, “TBS”, “DXA”, “ACTH”, “osteoporosis”, “osteopenia”, or “adrenal”. Core endocrine descriptive analysis as displayed in Table 1 was restricted to clinical studies with different levels of statistical evidence, in both paediatric and adult population with major BTH, including more than 40 participants/study aiming two types of data: the ratio of EDs among the general panel of complications; and correlations between EDs and other specific parameters of evaluation in BTH (we included 1 longitudinal study, 15 cross-sectional studies, 1 retrospective analysis, 1 cohort study, 2 meta-analysis, and 2 surveys) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ] ( Table 1 ).…”

“…A meta-analysis from 2021 included 74 studies concerning the growth status in patients with major BTH, between 1978 and 2019 (mean age of 14 y). The pooled prevalence of short stature was 48.9% (males more affected than females) and 26.6%, respectively, GH deficiency (95% CI 16-40.8) [ 25 ]. Half of the patients with a mean age of 14 y displayed different types of growth anomalies [ 25 , 27 ].…”

“…The pooled prevalence of short stature was 48.9% (males more affected than females) and 26.6%, respectively, GH deficiency (95% CI 16-40.8) [ 25 ]. Half of the patients with a mean age of 14 y displayed different types of growth anomalies [ 25 , 27 ]. Another study suggested that short stature is the most frequent ED—a cohort on 24 persons with major BTH (mean age of 21.7 ± 8 y) showed that, independently of severe liver IO, 26% of them had short stature, followed by 16% with pre-DM, 14% with subclinical hypothyroidism, 14% with hypogonadotropic hypogonadism, and 12.5% with DM [ 49 ].…”

“…Since the patients with intermediate BTH have different clinical presentations, EDs vary, and a subgroup of subjects was similar to patients with major BTH with regards to the profile of EDs [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. Overall, short stature affects both children and adults; GH/IG...…”