Birgit Borgström

Karolinska Institutet, Сольна, Stockholm, Sweden

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Publications (15)43.2 Total impact

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    ABSTRACT: The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies. The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this. The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country. © 2015 S. Karger AG, Basel.
    Full-text · Article · Jul 2015 · Hormone Research in Paediatrics
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    ABSTRACT: Treatment-related late toxicities after pediatric allogeneic hematopoietic SCT (allo-HSCT) are increasingly important as long-term survival has become an expected outcome for many transplanted children and adolescents. In a retrospective cohort study, we assessed long-term health outcomes in 204 allo-HSCT survivors transplanted in childhood or adolescence (<20 years) between 1978 through 2000 after a median follow-up time of 12 (range 4-28) years. Data on conditioning regimen, adverse health events (AE) and growth and hormonal substitutions (hormone replacement therapies (HRTs)) were obtained from medical records. AEs were graded retrospectively according to Common Terminology Criteria for Adverse Events v3.0. Late deaths (⩾48 months after allo-HSCT) were evaluated separately. Multivariate analysis demonstrated that chronic GVHD (P<0.000) and longer follow-up time (P<0.05) correlated with AEs, whereas CY-based conditioning was inversely correlated (P<0.002). TBI and longer follow-up duration predicted more severe AEs (P<0.001 and P<0.001, respectively). HRTs were more frequent after TBI. Diabetes type II, dyslipidemia and hypertension were detected in 9, 7 and 7% of the survivors, respectively. Late deaths (n=22) were most frequently due to pulmonary failure (n=7), followed by secondary malignancy (n=5). The occurrence of AEs after pediatric allo-HSCT is high and likely to increase during extended follow-up, particularly in patients who have received TBI.Bone Marrow Transplantation advance online publication, 23 March 2015; doi:10.1038/bmt.2015.43.
    No preview · Article · Mar 2015 · Bone marrow transplantation
  • K.A. Rodriguez-Wallberg · B. Borgström · O. Hovatta
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    ABSTRACT: In this manuscript, the development of the clinical program for fertility preservation for adults and children at Karolinska University Hospital is described. Novel indications for fertility preservation are presented as well as our experience with counseling of young individuals and our clinical experience with all procedures involved in fertility preservation of adults and children. The information gathered during the fertility preservation program (over 15 years) may contribute to the implementation of clinical routines for fertility preservation in other centers and should be of interest to physicians taking care of young patients with inherent risks of premature gonadal failure or who need to undergo medical or surgical treatments that may reduce the patient’s reproductive potential.
    No preview · Article · Aug 2014 · Lakartidningen
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    ABSTRACT: Background Testicular dysfunction and infertility are of major concern in long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). This study assesses predictive factors for very long-term testicular recovery after allogeneic HSCT in childhood and adolescence. ProcedureTesticular volume, sperm production and long-term need of testosterone substitution were evaluated among 106 male survivors transplanted at Huddinge and Helsinki University Hospitals from 1978 through 2000, at a mean age of 8 ± 4.6 years (range 1–17). A mean ± SD of 13 ± 4.8 years (range 4–28) had elapsed since their HSCT and the mean age of the participants was 22 ± 6.0 years (range 12–42). An adult testicular volume was recorded in 74 patients at a mean age of 19 ± 3.3 years (range 14–36). ResultsRecipients conditioned with busulfan-based regimens or regimens containing only cyclophosphamide had significantly larger adult testicular volumes (mean volume 18 ml and 16 ml vs. 9 ml, P
    No preview · Article · Jun 2014 · Pediatric Blood & Cancer
  • Kenny A Rodriguez-Wallberg · Birgit Borgström · Outi Hovatta

    No preview · Article · Apr 2014

  • No preview · Article · Oct 2012 · Growth Hormone & IGF Research
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    ABSTRACT: The long-term mortality in adults treated with recombinant GH during childhood has been poorly investigated. Recently released data from the French part of the European Union Safety and Appropriateness of GH treatments in Europe (EU SAGhE) study have raised concerns on the long-term safety of GH treatment. To report preliminary data on long-term vital status and causes of death in patients with isolated GH deficiency or idiopathic short stature or born small for gestational age treated with GH during childhood, in Belgium, The Netherlands, and Sweden. Data were retrieved from national registries of GH-treated patients and vital status from National Population Registries. Causes of death were retrieved from a National Cause of Death Register (Sweden), Federal and Regional Death Registries (Belgium), or individual patient records (The Netherlands). All patients diagnosed with isolated GH deficiency or idiopathic short stature or born small for gestational age started on recombinant GH during childhood from 1985-1997 and who had attained 18 yr of age by the end of 2010 were included. Vital status was available for approximately 98% of these 2,543 patients, corresponding to 46,556 person-years of observation. Vital status, causes of death, age at death, year of death, duration of GH treatment, and mean GH dose during treatment were assessed. Among 21 deaths identified, 12 were due to accidents, four were suicides, and one patient each died from pneumonia, endocrine dysfunction, primary cardiomyopathy, deficiency of humoral immunity, and coagulation defect. In these cohorts, the majority of deaths (76%) were caused by accidents or suicides. Importantly, none of the patients died from cancer or from a cardiovascular disease.
    No preview · Article · Feb 2012 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: One of the characteristic symptoms in girls and women with Turner syndrome (TS) is ovarian failure with infertility. Puberty starts spontaneously in 15% to 30% of girls with this syndrome but less than 5% reach menarche with the possibility of becoming pregnant because ovarian follicles secreting estrogen disappear prematurely. In a prior study, the investigators cryopreserved biopsy specimens from ovarian cortical tissue of adolescent girls with TS and found remaining follicles in 8 of 10 girls. This study investigated clinical and laboratory parameters that could help identify which girls with TS are likely to benefit from freezing of ovarian tissue to preserve fertility. The study subjects were 57 girls with TS, aged 8 to 19.8 years who had been referred to a fertility unit by 25 pediatric endocrinologists in Sweden. Ovarian cortical tissue was biopsied laparoscopically for follicle counts and cryopreserved. Parameters analyzed included karyotype, age at biopsy, spontaneous onset of puberty and menarche, number of follicles, and serum concentrations of follicle stimulating hormone, luteinizing hormone, and anti-Müllerian hormone. Among the 57 girls in the study, ovarian biopsy was feasible in 47, and follicles were identified in 15 (26%). Follicles were found in 6 of 7 (86%) girls with mosaicism, in 6 of 22 (27%) with structural chromosomal abnormalities, and in 3 of 28 (10.7%) with karyotype 45X. Signs of spontaneous onset of puberty were found in 19 girls, 11 of whom (58%) had follicles in the tissue. Menarche had been reached spontaneously in 13 girls; of these, 8 (62%) had follicles. Despite a high-negative predictive value for finding follicles in girls below 12 years, age was not a significant factor. These findings show that girls with TS who have the highest likelihood of having remaining follicles are those with mosaicism, spontaneous onset of puberty, and normal hormone concentrations.
    No preview · Article · Jun 2009 · Obstetrical and Gynecological Survey
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    ABSTRACT: Many girls with Turner syndrome have follicles in their ovaries at adolescence. Objective: Our objective was to study which girls might benefit from ovarian tissue freezing for fertility preservation. Design: Clinical and laboratory parameters and ovarian follicle counts were analyzed among girls referred by 25 pediatric endocrinologists. Fifty-seven girls with Turner syndrome, aged 8-19.8 yr, were studied at a university hospital. Interventions: Ovarian tissue was biopsied laparoscopically, studied for the presence of follicles, and cryopreserved. Blood samples were drawn for hormone measurements. Presence of follicles in the biopsied tissue related to age, signs of spontaneous puberty, karyotype, and serum concentrations of gonadotropins and anti-Müllerian hormone were assessed. Ovarian biopsy was feasible in 47 of the 57 girls. In 15 of the 57 girls (26%), there were follicles in the tissue piece analyzed histologically. Six of seven girls (86%) with mosaicism, six of 22 (27%) with structural chromosomal abnormalities, and three of 28 with karyotype 45X (10.7%) had follicles. Eight of the 13 girls (62%) with spontaneous menarche had follicles, and 11 of the 19 girls (58%) who had signs of spontaneous puberty had follicles. The age group 12-16 yr had the highest proportion of girls with follicles. Normal FSH and anti-Müllerian hormone concentrations for age and pubertal stage were more frequent in girls with follicles. Signs of spontaneous puberty, mosaicism, and normal hormone concentrations were positive and statistically significant but not exclusive prognostic factors as regards finding follicles.
    Full-text · Article · Nov 2008 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: To follow-up six children with severe mucopolysaccharidosis type IH, Hurler syndrome, who were treated before 24 months of age with haematopoietic stem cell transplantation. In Sweden, during the last 10-year period, six consecutive children born with severe mucopolysaccharidoses type IH have been successfully transplanted using matched unrelated donors between the ages of 11 and 24 months (mean age 18 months). Three children received intravenous enzyme replacement therapy once a week, from diagnosis until engraftment of their bone marrow. Two children developed chimerism and a progressive increase in recipient cells and later received a successful re-transplantation. One to two years after transplantation the children demonstrated some developmental delays in cognitive function. Latterly this was followed by normalization. Orthopaedic operations on the spine and hips and carpal tunnel syndrome were still required following transplantation. Cardiac valve involvement remained progressive in the children. The outcome of six children in this study confirms that early haematopoietic stem cell transplantation in mucopolysaccharidosis type I, Hurler syndrome, preserves an affected child's mental ability. Consequently, it is essential that clinical recognition and early diagnosis take place, providing an additional challenge to paediatricians treating this condition.
    No preview · Article · May 2008 · Acta Paediatrica
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    ABSTRACT: A 7-year-old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160,000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C-peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5- and 27-months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C-peptide levels were 0.67 +/- 0.07 and 3.36 +/- 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long-term clinically significant metabolic control.
    Full-text · Article · Mar 2008 · American Journal of Transplantation
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    ABSTRACT: Banking of testicular tissue from pre-pubertal boys before gonadotoxic treatment is a crucial step in fertility preservation. We wanted to find optimal methods for cryopreservation of testicular tissue from pre-pubertal boys, modifying techniques developed for fetal and adult human testicular tissue cryopreservation. Testicular tissue was collected from five pre-pubertal boys undergoing gonadotoxic treatment in a clinical programme. Two freezing protocols, originally developed for fetal and adult human testicular tissue, were applied for pre-pubertal testicular tissue cryopreservation. In both methods, 5% dimethyl sulphoxide (DMSO) was used as a cryoprotectant. The integrity of the tissue was investigated in non-frozen tissue cultured for 24 h and in cryopreserved-thawed tissue, using two different programmes. We also analysed frozen-thawed samples cultured for 24 h in comparison with untreated fresh fixed control tissue. Immunohistochemical analysis using anti-MAGE-A4, vimentin and CD34 monoclonal antibodies was performed in order to visualize and characterize the cryodamage of the different testicular cells and compartments. The structure of the tissue was evaluated using light microscopy. Qualitative control analysis was performed using transmission electron microscopy. No clear structural changes were observed in the fresh, fresh cultured and cryopreserved testicular tissue after using the protocol developed for adult testicular tissue. The programme earlier successfully used for human fetal testicular tissue cryopreservation caused more tissue damage. Pre-pubertal testicular tissue from boys facing gonadotoxic treatment survives cryopreservation, can be cryobanked and hopefully used for fertility preservation. Slow programmed freezing with DMSO as a cryoprotectant is efficient in maintaining the spermatogonia, Sertoli cells and stromal compartment during freezing, thawing and tissue culture.
    Full-text · Article · Jun 2007 · Human Reproduction
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    ABSTRACT: In Turner syndrome, about a third of the diagnosed girls undergoes at least some pubertal development, and up to 5% are fertile. About 50% of Turner syndrome girls have follicles in their ovaries. The likelihood to have them is highest among mosaic Turner syndrome girls who have signs of spontaneous puberty, but also 25% of the non-mosaic Turner girls have them. Hence, cryopreservation of ovarian cortical tissue for infertility treatment in the future is possible. Oocyte donation is an effective option for Turner Syndrome women to obtain children. Pregnancy rates of 30–60% per embryo transfer have been reported. Single embryo transfer is a requirement, because twin pregnancies bear higher risk of pre-eclampsia and impaired glucose tolerance, and Turner women are already a high risk group for such problems. To avoid complications during pregnancies, a cardiology control including magnetic resonance imaging has to be carried out before planned pregnancies. 1. Ovarian function and spontaneous pregnancies Normal numbers of eggs develop in girls with Turner syndrome during fetal life, but a majority of them often disappear prematurely [1–3]. The cause is not known, but it has been suggested that the abnormal oocytes without normal second X-chromosome are not viable. Up to 30% of Turner girls have at least some grade of spontaneous puberty, and some 10% reach menarche, and some 2–5% have been estimated to be fertile [4–6].This may, however, be a too low number. Many of the fertile Turner syndrome women have apparently been undiagnosed. A case report from Sweden [7] demonstrates this.
    Full-text · Article · Oct 2006 · International Congress Series
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    ABSTRACT: Infertility caused by ovarian failure is a characteristic feature in Turner's syndrome. Spontaneous pregnancies are seen in 2-5% of these women, and up to 30% have at least some pubertal development, indicating the presence of follicles in their ovaries in adolescence. It has not been clear at which age the follicles disappear. We analyzed the numbers and densities of follicles in ovarian cortical tissue from nine adolescent girls with Turner's syndrome who came to our clinics after having been informed about the study, with an aim to preserve ovarian tissue for possible infertility treatment later in life. A quarter to one whole ovary was laparoscopically removed for the procedure. Follicles were seen in the biopsy tissue in eight of nine subjects from whom ovarian tissue was laparoscopically obtained, the highest numbers being seen in the youngest girls and in those with mosaicism. In one 17-yr-old girl, no ovarian tissue was found. Follicle density was correlated with serum levels of FSH; individuals with the lowest FSH levels had the highest follicle density. One to 190 follicles were counted in the approximately 0.1-2.0 mm(3) of tissue analyzed, giving a density of 1.5-499 follicles/mm(3) of ovarian cortical tissue. Girls up to the age of 17 had primordial follicles in their ovaries. Three girls, two aged 15 yr and one aged 19, had only secondary follicles, with many being atretic. Our finding that adolescent girls with Turner's syndrome still have follicles in their ovarian cortical tissue raises the possibility of future fertility through cryopreservation of ovarian tissue. However, before such procedures can be recommended for clinical management, it is essential that future studies be performed to determine whether the oocytes retrieved from girls with Turner's syndrome have a normal chromosomal complement.
    Full-text · Article · Sep 2002 · Journal of Clinical Endocrinology & Metabolism
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    Gerd Holmström · Birgit Borgström · Berit Calissendorff
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    ABSTRACT: To compare the frequency of cataract development in bone marrow transplanted children who have been given either total body irradiation (TBI) or busulphan as conditioning treatment before bone marrow transplantation (BMT). Forty-five children who underwent BMT between 1987 and 1994 were included in the study. Twenty-one children were conditioned with TBI and 24 with busulphan before BMT. All children underwent an ophthalmic examination before BMT in order to exclude lens opacities. Yearly examinations for 2-10 years were performed after BMT. Cataracts developed in 20 of the 21 (95%) children conditioned with TBI and in five of the 24 (21%) children conditioned with busulphan. There was no relationship between cataract development and age at BMT, or between cataract development and prednisolone given before or after BMT. The present study confirms earlier reports of the high risk of cataract development after TBI and suggests that busulphan is related to cataract development, although less frequently than TBI. The report discusses the possible additive effect of the disease itself, of any corticosteroid treatment and of other cytostatic drugs. It then stresses the importance of early diagnosis of cataracts in children in order to prevent the development of amblyopia.
    Preview · Article · May 2002 · Acta Ophthalmologica Scandinavica

Publication Stats

479 Citations
43.20 Total Impact Points


  • 2006-2015
    • Karolinska Institutet
      • Department of Clinical Science, Intervention and Technology
      Сольна, Stockholm, Sweden
  • 2002-2015
    • Karolinska University Hospital
      • Department of Obstetrics and Gynecology
      Tukholma, Stockholm, Sweden
    • University of Helsinki
      • The Hospital for Children and Adolescents
      Helsinki, Uusimaa, Finland
  • 2008
    • Stockholm University
      Tukholma, Stockholm, Sweden