Growth and Adult Height in Girls With Turner Syndrome Following IGF-1 Titrated Growth Hormone Treatment.

CONTEXT: Girls with Turner syndrome (TS) suffer linear growth failure, and TS is a registered indication for growth hormone (GH) treatment. GH is classically dosed according to body weight, and serum insulin-like growth factor-1 (IGF-1) concentrations are recommended to be kept within references according to international guidelines. OBJECTIVE: To assess the effect of long-term GH treatment in girls with TS following GH dosing by IGF-1 titration. DESIGN AND SETTING: A retrospective, real-world evidence, observational study consisting of data collected in a single tertiary center from 1991 to 2018. PATIENTS: A cohort of 63 girls with TS treated with GH by IGF-1 titration with a median duration of 6.7 years (interquartile range [IQR]: 3.4-9.7 years). MAIN OUTCOME MEASURES: Longitudinal measurements of height, IGF-1, and adult height (AH) following GH treatment were evaluated and compared between the different karyotypes (45,X, 45,X/46,XX, or miscellaneous). RESULTS: Using GH dose titration according to IGF-1, only 6% of girls with TS had supranormal IGF-1 levels. Median dose was 33 µg/kg/day (IQR: 28-39 µg/kg/day) with no difference between the karyotype groups. AH was reached for 73% who attained a median AH of 1.25 standard deviation score (SDS) for age specific TS references (IQR: 0.64-1.50 SDS), and a median gain in height (ΔHSDS: AH SDS minus baseline height SDS of TS references) of 0.50 SDS, equal to 3.2 cm (SD 7.68) for all karyotypes. CONCLUSION: Our real-world evidence study suggested that titration of GH dose to keep IGF-1 levels within the normal range resulted in a lower AH gain than in studies where a fixed dose was used.

Changes of bone density in pediatric patients with ß-thalassemia major after allogenic hematopoietic stem cell transplantation.

BACKGROUND: Thalassemia major and its treatment by stem cell transplantation can have deleterious effects on bone integrity. This study assesses the adverse effects of transplantation on growing bones of pediatric thalassemic patients. METHODS: Bone mineral density (BMD) of 20 patients from three thalassemia classes whose mean (SD) age was 7.4 (3.8) years were tested with a Norland XR-46 device at baseline (before transplantation), 6 and 12 months after transplantation. RESULTS: At 6 and 12 months after transplantation we observed no significant changes in mean BMD. There were no Z-scores less than -2 among patients. Class 3 thalassemia did not negatively impact BMD. Calcium (Ca), phosphorous (P) and ferritin levels were not significantly related to patients' BMD scores. Transfusion duration and chelation therapy showed positive significant relationships to BMD (g/cm(2)), but no significant relation with the BMD Z-score. The deleterious relation between corticosteroid use and changes in BMD was not significant. In contrast, patients who developed acute graft versus host disease (aGVHD) after transplantation showed significant adverse effects on BMD of their femur (P = 0.020) and spine (P = 0.027). CONCLUSION: Stem cell transplantation in pediatric thalassemic patients who do not develop aGVHD does not appear to have any significant positive or negative effects on BMD.

Congenital anomalies in infants conceived by assisted reproductive techniques.

BACKGROUND: Many studies show that congenital defects in infants conceived by assisted reproductive techniques (ART) are more than infants of normal conception (NC). The aim of this study is to determine the frequency of congenital anomalies in ART infants from Royan Institute and to compare congenital anomalies between two ART techniques.  METHODS: In a cross-sectional descriptive study, 400 ART infants from Royan Institute who resided in Tehran were selected by non-random, consecutive sampling. Infants were examined twice (until 9 months of age) by a pediatrician. Infants' congenital anomalies were described by each body system or organ and type of ART. Data were analyzed by SPSS version 16 and Fisher's exact test. RESULTS: The frequency of different organ involvement in the two examinations were: 40 (10%) skin, 25 (6.2%) urogenital system, 21 (5.2%) gastrointestinal tract, 13 (3.2%) visual, and 8 (2%) cardiovascular system. Major congenital defects in infants conceived by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) were hypospadiasis, inguinal hernia, patent ductus arteriosus plus ventricular septal defect (PDA + VSD), developmental dysplasia of the hip, lacrimal duct stenosis during the first year of life, hydronephrosis and urinary reflux over grade III, undescending testis, ureteropelvic junction stenosis, and torticoli. CONCLUSIONS: Two-thirds of ART infants had no defects. A total of 7% of IVF and ICSI infants had one of the major abovementioned congenital anomalies. This rate was higher than NC infants (2%-3%). There was no difference between the ICSI and IVF group.

Prelinguistic behavior of infants of assisted reproductive techniques.

OBJECTIVE: The aim of this study is assessment of effects of different assisted reproductive techniques (ART) like in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) on prelinguistic behavior of infants conceived by these techniques. METHODS: In this descriptive, cross sectional study, prelinguistic behavior of 151 full term ART infants of Royan Institute have been assessed in Children's Health and Development Research Center of Tehran from August 2007 until August 2009. Questionnaires were completed by parents at 9 months old. The questionnaire was standard according to Early Language Milestone Scale-2 (ELM-2). Data were analyzed by SPSS version 16 and using chi-square test. FINDINGS: Twenty-two (14.5%) of infants were conceived by IVF and 129 (85.4%) by ICSI. Number of infants with delay in reduplicated babbling in ICSI method was more than in IVF. There was only a significant difference in echolalia delay in the two sexes. Echolalia was delayed more in boys. Delay of reduplicated babbling was more in infants of younger mothers. There was no relation between speech and language defect of parents and infants. CONCLUSION: This study showed that prelingustic behavior of ART infants are affected by kind of ART method, infant sex, and mother's age at the time of pregnancy.

Peripheral blood versus bone marrow as a source of hematopoietic stem cells for allogeneic transplantation in children with class I and II beta thalassemia major.

Peripheral blood stem cell transplantation (PBSCT) has been extended to treating hematologic disorders, but the benefits over bone marrow transplantation (BMT) still remain unclear, especially in nonmalignant hematologic disorders. In this study, we compared class I-II thalassemic children who underwent HLA-matched PBSCT and BMT for treatment. Conditioning regimens consisted of busulfan and cyclophosphamide, followed by cyclosporine +/- methotrexate for graft-versus-host disease (GVHD) prophylaxis. Using multivariate analysis, the outcomes of 87 PBSCT patients and 96 BMT patients were reported (median follow-up: 29 and 60 months, respectively). The median time to neutrophil and platelet recovery in PBSCT patients (11 and 18 days, respectively) was significantly lower than BMT patients (19 and 26 days, respectively) (P < .001). Grade II-IV acute GVHD was more frequent in PBSCT versus BMT group (72% versus 55%; P = .003) (relative risk = 1.75, 95% confidence interval [CI]: 1.20-2.57). The incidence of chronic GVHD was more frequent in the PBSCT versus BMT group (48% versus 19%; P < .001) (relative risk = 2.62, 95% CI: 1.43-4.82). There was no difference in the 2-year overall survival after PBSCT and BMT (83% and 89%, respectively). The 2-year disease-free survival was 76% in both groups. These results show some advantages of PBSCT, but to improve the risk of GVHD in PBSCT, a better conditioning and prophylaxis regimen is needed.