Natural history of infants with vitamin D deficiency in Hong Kong.

BACKGROUND AND OBJECTIVES: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD. METHODS AND STUDY DESIGN: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected. RESULTS: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L). CONCLUSIONS: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation.

Awareness of diagnosis, treatment and risk of late effects in Chinese survivors of childhood cancer in Hong Kong.

BACKGROUND: For survivors of childhood cancer, awareness of personal health risks is a critical component of long-term health management. OBJECTIVE: To evaluate the awareness of the diagnosis, treatment and risk of late effects among survivors of childhood cancer in Hong Kong. METHODS: Between June 2019 and March 2020, this cross-sectional study recruited 155 adult survivors (mean age = 26.9, standard deviation [SD] = 6.4 years) and 45 parents of paediatric survivors (mean age = 11.1, SD = 3.6 years) from a long-term follow-up clinic. At >10 years post-treatment (mean = 13.4, SD = 7.6 years), they completed a structured questionnaire to report their cancer-specific knowledge. Multiple linear regression analysis was conducted to identify clinical, socioeconomic and behavioural factors associated with poor awareness. RESULTS: The majority of participants accurately recalled their diagnoses (73.5%) and major treatment modalities (chemotherapy 92.4%, radiation 82.9% and surgery 88.2%). However, less than half (45%) of the participants recognized more than 25% of the total late effects for which they were at risk. The highest levels of awareness were reported for endocrine problems (49%), neurocognitive impairment (44%) and secondary cancers (43%), and the lowest for peripheral neuropathy (21%) and vision problems (23%). Compared with survivors of haematological malignancies, those of central nervous system (CNS) tumours (standardized estimate [B] = -9.33, 95% confidence interval [95% CI]: -13.41 to -5.26) and non-CNS solid tumours (B = -8.47, 95% CI: -12.39 to -4.94) had less knowledge about their diagnosis. Retaining medical records (P < .0001) and better medical information-seeking habits (P = .048) were associated with better awareness. CONCLUSIONS: Survivors of childhood cancer in Hong Kong have deficient awareness of their personal health risks. They may benefit from the provision of a survivorship care plan and personalized education regarding treatment-related late effects. PATIENT CONTRIBUTION: Patients contributed in designing the study tools. Results were presented at a non-governmental organization.

Spontaneous pregnancies in female survivors of childhood allogeneic haemopoietic stem cell transplant for haematological malignancies.

OBJECTIVE: Spontaneous pregnancies and live births are rarely reported after haematopoietic stem cell transplant (HSCT). We report spontaneous pregnancy outcomes of sexually active female survivors of childhood allogeneic HSCT, to provide more data for future counselling. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of all female survivors of childhood haematological malignancies who had allogeneic HSCT at the Royal Children Hospital between 1985 and 2011. Data were retrieved from medical records, updated from treating haematologist or endocrinologist, and were cross-referenced with self-reported questionnaires. Female survivors who were sexually inactive were excluded from analysis. RESULTS: Six of 37 (16.2%) female survivors reported spontaneous pregnancies resulting in 8 live births. Amongst 22 women who received total body irradiation (n = 21) ± cranial irradiation or isolated cranial irradiation (n = 1), and high-dose cyclophosphamide, three reported pregnancy resulting in live births (14%), whilst three of 15 women who received chemotherapy alone had pregnancy with live births (20%). CONCLUSIONS: Our current finding, albeit a small sample size, reinforces the importance of counselling female survivors of HSCT about the possibility of spontaneous pregnancy occurring despite documented ovarian failure and for need of contraception to avoid unplanned pregnancy.

The late effects of haematopoietic stem cell transplants in paediatric patients: a 25 year review.

CONTEXT: A rare, large single centre study covering all long-term health outcomes of paediatric allogeneic HSCT survivors, to provide comprehensive local data, and identify gaps and future directions for improved care. OBJECTIVE: To document endocrine sequelae and other late effects of all HSCT recipients. DESIGN: Retrospective review. SETTING: Royal Children's Hospital Melbourne. PATIENTS: 384 children and adolescents received HSCT. 228 formed the study cohort; 212 were alive at commencement of data accrual. INTERVENTION: None. MAIN OUTCOME MEASURES: Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). RESULTS: Gonadotoxicity was more common in females (p<0.001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses (CED) developed premature ovarian insufficiency (POI) . In males, impaired spermatogenesis +/- testicular endocrine dysfunction was associated with increasing testicular radiation exposure. Preservation of gonadal function was associated with younger age at HSCT. Of sexually active females, 22% reported spontaneous pregnancies. Short stature was common, with growth hormone axis disruption in 30% of these. Of patients exposed to thyroid radiation 51% developed nodules, 30% malignant. Metabolic disturbances included hypertension, dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6%; avascular necrosis in 6%. 13% developed SMNs, risk continuing to rise throughout follow-up. CONCLUSIONS: We confirm gonadal dysfunction, multiple endocrine and metabolic abnormalities, thyroid cancer and SMNs, as common sequelae of HSCT, and identify gaps in management - particularly the need for informed fertility counselling and pretreatment fertility preservation, evaluation and management of bone health, and underline need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.

Prevalence and risk factors of fractures in transfusion dependent thalassemia - A Hong Kong Chinese population cohort.

OBJECTIVE: To delineate the prevalence and associated risk factors of low BMD, osteoporosis/bone fragility and fracture in transfusion-dependent thalassemia (TDT) in the Chinese population in Hong Kong. DESIGN, PATIENTS AND MEASUREMENTS: A retrospective cohort study design was employed. Patients of TDT who had serial Hologic dual-energy X-ray absorptiometry (DXA) from 2010 to 2016 and received regular transfusion for at least 5 years were recruited. Clinical and biochemical data, from 5 years before the first DXA scan, were retrieved from the electronic record system of the Hospital Authority, till 30 June 2020. Low bone mineral density and osteoporosis/bone fragility are defined by the ISCD 2019 position guidelines. RESULTS: Seventy-seven patients were included in the analysis. The fracture prevalence of TDT among the Chinese population in Hong Kong was 15.58%. Up to 55.84% of patients had low bone mineral density, and 5.19% patients had osteoporosis/bone fragility state. The median age at first fracture was 31.73 years (range 24.06-44.18 years). In the regression analysis, a higher log(10) transformation of average ferritin levels over 5 years before the first DXA scan was significantly associated with fracture occurrence regardless of bisphosphonate treatment (OR 310.73, 95% CI 3.99-24183.89, p = .010). Mean average ferritin level over 5 years was 6695.5 ± 2365.7 pmol/L (fracture group) versus 4350.7 ± 3103.2 pmol/L (non-fracture group), p = .016. Hip and spine BMD Z-score did not have statistically significant association with fracture occurrence. CONCLUSION: Iron overloading plays an important role in adverse bone health in TDT. Dual X-ray densitometry is insufficient in predicting fracture risk.

Perceptions of Infertility Risk Among Chinese Parents of Children with Cancer: A Qualitative Study.

Objective: Anticancer treatment may be associated with damage to the reproductive organs and risk of infertility in children with cancer. The collectivist cultural norms of Asian societies may lead Chinese parents to have unique concerns regarding infertility. This qualitative study explored the perceptions of infertility risk and parenthood among parents of childhood cancer survivors in Hong Kong. Methods: Thirteen parents were recruited via a snowball sampling approach from a nongovernmental organization in Hong Kong, representing nine survivors of childhood cancer (leukemia n = 5, solid tumors n = 4). The in-depth semistructured interviews were audiotaped and transcribed verbatim. A thematic analysis was performed using ATLAS.ti 8. Results: Parents mostly perceived their children's fertility status as a distant concern (n = 11, 85%) but emphasized the need for timely information from clinicians when their children reach young adulthood (n = 8, 62%). They reported receiving inconsistent fertility information from different oncology practitioners (n = 9, 69%). A few parents acknowledged that under the influence of the Chinese culture, their children, especially sons, have an important duty to continue the family lineage. However, even if the cancer treatment were associated with infertility risk, almost all parents (n = 12, 92%) stated that it would still not affect their willingness to let their child undergo treatment because survival and cure were still their highest priority. Conclusion: Our findings suggest the need to proactively provide fertility information to parents both during active treatment and when survivors reach reproductive age. Future studies should evaluate the benefits of developing culturally relevant decision-making aids to address parents' informational needs regarding fertility issues.

Medication Burden Among Pediatric Cancer Survivors: Analysis of a Population-Wide Electronic Database in Hong Kong.

BACKGROUND: Few studies have evaluated the medication burden borne by survivors of pediatric cancer. This study aimed to describe the drug utilization pattern of chronic medications in a cohort of young pediatric cancer survivors. METHODS: This was a population-based study of patients diagnosed with cancer at age 18 years or younger between 2000 and 2013 in Hong Kong and who had survived at least 5 years postdiagnosis. The primary outcome is the use of any chronic medication (medications that were prescribed for ≥30 consecutive days within a 6-month period). Multivariable log-binomial models were used to identify factors associated with chronic medication use. Kaplan-Meier analysis was used to present the cumulative proportion of survivors initiated on a chronic medication across time from cancer diagnosis. RESULTS: Of the 2444 survivors (median age = 22 years, interquartile range = 16-27 years), 669 (27.4%) required at least 1 chronic medication at least 5 years postdiagnosis. Survivors who developed a chronic health condition (CHC) had a 5.48 (95% confidence interval [CI] = 4.49 to 6.71) times higher risk of taking a chronic medication than those without CHC. At 10 years postdiagnosis, the cumulative proportion of survivors being initiated a chronic medication was 33.4% (95% CI = 31.1% to 35.6%) for the overall cohort. Higher cumulative proportions were observed in survivors with endocrine (74.6%, 95% CI = 68.4% to 79.6%), renal (68.8%, 95% CI = 54.2% to 78.7%), neurological (58.6%, 95% CI = 46.1% to 68.1%), and cardiovascular (54.7%, 95% CI = 44.0% to 63.4%) disorders. CONCLUSION: Survivors with certain CHCs had a higher risk of starting a prescription medication in the early phase of survivorship. Future studies include examining the impact of medication burden on survivors' functional status.

Outcomes of Zoledronic Acid Use in Paediatric Conditions.

INTRODUCTION: Limited evidence is available concerning experience with use of zoledronic acid (ZA) and treatment for conditions other than primary bone fragility. MATERIALS AND METHODS: A retrospective review of all Royal Children Hospital patients who had been administered at least 1 dose of intravenous ZA from 2002 to 2015 was undertaken. RESULTS: The audit included 309 children with 228 being treated for bone fragility conditions. Of the 228, 68 had height-adjusted lumbar spine bone mineral density Z-scores available over up to a 5-year period, and median increases were +2.0 SD (median absolute deviation = 0.9) (N = 36, p value for median increase of at least 0.5 in Z-score <0.001), for patients with osteogenesis imperfecta or other primary bone fragility disorders, +1.0 SD (0.9) (N = 14, p = 0.029), for immobility conditions, +0.5 SD (0.7) (N = 10, p = 0.399), and for glucocorticoid-induced secondary osteoporosis, +0.7 SD (0.6) (N = 8, p = 0.015). 81/309 children were treated for bone abnormality indications (e.g., avascular necrosis [AVN], fibrous dysplasia, and bone cysts). Of 39 with AVN, outcome data were available for 33, with joint integrity maintained for 24/33 from 6 to 24 months after last ZA, subjective reports (22/28) of reduced pain. Reduction in bone lesion size was seen in 2/4 patients with bone cysts within 12 months of ZA commencement. DISCUSSION/CONCLUSION: This is the largest cohort of reported outcomes of ZA use in a paediatric population. Results demonstrate a good efficacy profile and associated improved bone density for osteoporotic conditions and stabilization of non-traumatic AVN with a low rate of joint collapse.

Effect of Testosterone Treatment for Delayed Puberty in Duchenne Muscular Dystrophy.

OBJECTIVE: To evaluate the impact of pubertal induction with testosterone on bone health, body composition, and motor function in boys with Duchenne muscular dystrophy (DMD) receiving long-term glucocorticoid. STUDY DESIGN: A retrospective, observational, pre-post study investigating the impact of testosterone therapy on bone mass accrual, vertebral fracture incidence, body composition, motor function, and quality of life in boys with DMD. All those boys aged ≥14 years, on chronic steroid therapy, who had delayed puberty, and were receiving oral testosterone or oral and then transitioned to intramuscular testosterone, to complete virilization, were included. Prior/concomitant zoledronic acid use was included. The primary outcome was lumbar spine areal bone mineral density (BMD LS). RESULTS: Puberty was induced, using oral testosterone undecanoate in 16 individuals, 10 of whom had transited to intramuscular testosterone at time of assessment. Median age at testosterone onset was 14.5 years (range 14-17.7). Median duration of testosterone therapy was 2.5 years (range 1.0-4.5). There was statistically significant increase in median BMD LS (0.523-0.700, p < 0.001) and median annualized percentage change of BMD LS (-1.34 to +10.08%, p < 0.001), with median Tanner stage 4 at evaluation (range 2-4). Ten of 14 assessed had no progression in vertebral fractures. Fat mass index (FMI) standard deviation score (SDS), lean body mass index (LBMI) SDS, and percentage change of FMI and LBMI were statistically unchanged. Cardiac function remained stable. Motor function in non-ambulatory individuals with Egen Klassifikation scores improved in 7 of 8. CONCLUSION: Testosterone for delayed puberty acted as an adjunct to bisphosphonates to increase bone density and stabilize vertebral fracture in most boys with DMD.