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Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease.

This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2–17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen.

Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes −45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure.

In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.

Aim: We aimed to evaluate the occurrence of, and risk factors for precocious and early puberty in a retrospective cohort study of girls with shunted infantile hydrocephalus.

Methods: The study population comprised 82 girls with infantile hydrocephalus, born between 1980 and 2002, and treated with a ventriculoperitoneal shunt. Data were available for 39 girls with myelomeningocele and 34 without. Medical records were analysed regarding clinical data and timing of puberty. Precocious and early puberty was defined as the appearance of pubertal signs before 8 years and 0 months and 8 years and 9 months, respectively.

Results: Median age at last admission was 15.8 years (range 10.0–18.0). In total, 15 girls (21%) had precocious puberty, and another 21 (29%) had early puberty. Three or more shunt revisions had been performed in 26/36 girls with early or precocious puberty and in 3/37 girls without (p = 0.01). The number of shunt revisions correlated negatively with age at the start of puberty in the girls with myelomeningocele (Spearman's correlation coefficient = −0.512, p = 0.001).

Conclusion: Girls with shunted infantile hydrocephalus have a high risk of precocious or early puberty. Repeated shunt revisions seemed to be associated with early puberty.

This study aimed to investigate how maternal birthweight is related to early pregnancy obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Females born term and singleton in Sweden between 1973 and 1995 (N = 305,893) were studied at their first pregnancy. Information regarding their birthweight, early pregnancy body mass index, and pregnancy complications was retrieved from the Swedish Medical Birth Register, as were data on their mothers and offspring. High maternal birthweights (2-3 standard deviation scores (SDS) and >3 SDS) were associated with greater odds of early pregnancy obesity, odds ratio (OR) 1.52 (95% confidence interval (CI) 1.42-1.63) and OR 2.06 (CI 1.71-2.49), respectively. A low maternal birthweight (<2 SDS) was associated with greater odds of GDM (OR 2.49, CI 2.00-3.12). No association was found between high maternal birthweight and GDM. A maternal birthweight 2-3 SDS was associated with offspring birthweight 2-3 SDS (OR 3.83, CI 3.44-4.26), and >3 SDS (OR 3.55, CI 2.54-4.97). Corresponding ORs for a maternal birthweight >3 SDS were 5.38 (CI 4.12-7.01) and 6.98 (CI 3.57-13.65), respectively. In conclusion, a high maternal birthweight was positively associated with early pregnancy obesity and offspring macrosomia. A low, but not a high maternal birthweight, was associated with GDM.

Introduction: Growth hormone (GH) is a central hormone for regulating linear growth during childhood and also highly involved in the metabolism of lipids, carbohydrates, and protein. However, few studies report on how treatment with GH during childhood influences metabolic parameters. Our aim was to investigate metabolic effects of different doses of GH in short children with GH peak levels in the low to normal range. Design: Thirty-five prepubertal short children (<-2.5 SDS), aged 7-10 years, with peak levels of GH between 7 and 14 mu g/L during an arginine-insulin tolerance test, were randomized to 3 different doses (11/33/100 mu g/kg/day) of GH treatment for 2 years. Auxological and metabolic investigations were performed. These included metabolites in blood and interstitial microdialysis fluid, dual-energy X-ray absorptiometry, frequently sampled intravenous glucose tolerance test (FSIVGTT), and stable isotope examinations of rates of glucose production and lipolysis. Results: At 24 months, the high-dose group (HD) had higher fasting insulin compared with the standard-dose (SD) and low-dose (LD) groups (HD: 111.7 vs. SD: 61.2 and LD: 46.0 pmol/L [p < 0.001]) and showed signs of insulin resistance (HOMA-IR, HD: 4.20 vs. SD: 2.17 and LD: 1.71 (LD) [p < 0.001]). The FSIVGTT also demonstrated higher acute insulin response (p < 0.05). Few other metabolic differences were found at 24 months, but a decreased insulin sensitivity index (Si) could already be seen at 12 months for both SD and HD compared with the LD group (p < 0.05). Conclusion: Treatment with GH resulted in a dose-dependent decrease in insulin sensitivity, demonstrated by higher levels of fasting insulin and signs of insulin resistance in both HOMA indices and FSIVGTT examinations.

Aim To investigate the prevalence of vitamin D deficiency among children with non-haematological malignancies and to explore possible causes of low vitamin D levels among these patients. Methods We performed a cross-sectional study of 458 children diagnosed with solid tumours, brain tumours, non-Hodgkin lymphoma or Hodgkin disease at the University Children's Hospital, Uppsala, Sweden. Serum 25-hydroxyvitamin D and parathyroid hormone levels were measured in samples taken at the time of cancer diagnosis and related to clinical data. Vitamin D deficiency was defined as a 25-hydroxyvitamin D level below 50 nmol/L. Results The prevalence rate of vitamin D deficiency among children with non-haematological malignancies was 41%. There was no association between sex or diagnosis and vitamin D status. Vitamin D deficiency was more common among school children than preschool children (51% vs. 24%). Older age, season outside summer, and a more recent calendar year were significant predictors of lower 25-hydroxyvitamin D. There was a significant, albeit weak, negative correlation between 25-hydroxyvitamin D and parathyroid hormone. Conclusion Vitamin D deficiency is common among children diagnosed with cancer, particularly among school-aged children diagnosed outside summer. The prevalence appears to be increasing, underlining the need for adequate replacement of vitamin D in these patients.

BACKGROUND: Children and adolescents with leukemia are potentially at high risk of vitamin D inadequacy, which may have clinical relevance for skeletal morbidity, infections, and cancer outcome. This study aimed to evaluate vitamin D status at the time of diagnosis to investigate its predictors and association with overall survival in children with leukemia. PROCEDURE: We included all 295 children and adolescents diagnosed with leukemia at our institution between 1990 and 2016 who had available serum sample from the time of diagnosis. We analyzed serum 25-hydroxyvitamin D and parathyroid hormone levels and correlated them with clinical data. RESULTS: The 25-hydroxyvitamin D level was deficient (< 25 nmol/L), insufficient (25-50 nmol/L), sufficient (50-75 nmol/L), and optimal (> 75 nmol/L) in 6.4%, 26.8%, 39.7%, and 27.1% of the children, respectively. Older age and a more recent time of sampling (calendar year) predicted lower 25-hydroxyvitamin D level. In preschool children (age </=6 years), lower 25-hydroxyvitamin D level was also associated with acute myeloid leukemia, and a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival. In school-aged children (age > 6 years), the 25-hydroxyvitamin D level showed significant seasonal variation. CONCLUSION: It remains unclear whether vitamin D supplementation in pediatric leukemia patients will improve outcome.

Purpose: To evaluate whether an intervention, targeting deficits in social communication, interaction and restricted activities in children and adolescents with Down syndrome and autism could lead to enhanced participation in family and school activities.

Methods: The intervention included education for parents and school staff about autism, and workshops to identify social-communication and daily living activities that would be meaningful for the child to practice at home and at school. Thereafter, a three-month period of training for the child followed. Outcome measures comprised evaluation of goal achievement for each child, the “Family Strain Index” questionnaire and a visual scale pertaining to the parents´ general opinion about the intervention.

Results: On average, more than 90% of the goals were (to some extent or completely) achieved at home and at school. The mean scores of the “Family Strain Index” were almost identical at the follow-up to those before intervention. The evaluation supported that the use of strategies, intended to facilitate activities and communication, remained largely 18 months after start of the intervention.

Conclusion: Despite the group involved in this study being comprised of older children and adolescents, most of whom had severe and profound intellectual disability, the goal achievements and parents’ views on the intervention were encouraging.

Aim: To compare levels and profiles of autistic symptoms in children with Down syndrome (DS) with diagnosed autism spectrum disorder (ASD), with those with DS without ASD and with children with idiopathic autism.

Methods From a population-based cohort of 60 children with DS (age 5-17 years) with 41 participating, those with ASD were compared to those without ASD using the scores obtained with the Autism Diagnostic Observation Schedule (ADOS) Module-1 algorithm.

Results: Children with both DS and ASD had significantly higher ADOS scores in all domains compared to those without ASD. When the groups with DS, with and without ASD, were restricted to those with severe intellectual disability (ID), the difference remained. When the children with DS and ASD were compared with a group with idiopathic autism, the ADOS profile was broadly similar.

Conclusion: A considerable proportion of children with DS, exhibit autism in addition to severe ID. In addition, there is also a group of children with DS and severe ID, but without autism. There is a need to increase awareness of the high prevalence of autism in children with DS. Recognizing the prevalence of autism is important for the appropriate diagnosis and care of children with DS.

Context: GH responsiveness guides GH dosing during the catch-up growth (CUG) period; however, little is known regarding GH dosing during the prepubertal maintenance treatment period.

Objective: To evaluate whether SD score (SDS) channel parallel growth with normal height velocity can be maintained after CUG by reducing the GH dose by 50% in children receiving doses individualized according to estimated GH responsiveness during the catch-up period.

Design and Settings: Prepubertal children (n = 98; 72 boys) receiving GH during CUG (GH deficient, n = 33; non-GH deficient, n = 65), were randomized after 2 to 3 years to either a 50% reduced individualized dose (GH^RID; n = 27; 20 boys) or unchanged individualized dose (GH^UID; n = 38; 27 boys). Another 33 children (25 boys) continued a standard weight-based dose [43 μg/kg/d (GH^FIX)].

Main Outcome Measures: The primary endpoint was the proportion of children with Δheight_SDS within ±0.3 at 1 year after GH dose reduction compared with two control groups: GH^UID and GH^FIX. The hypothesis was that height_SDS could be maintained within ±0.3 with a reduced individualized GH dose.

Results: For the intention-to-treat population at 1 year, 85% of the GH^RIDgroup maintained Δheight_SDS within ±0.3 vs 41% in the GH^UIDgroup (P = 0.0055) and 48% in the GH^FIXgroup (P = 0.0047). The ΔIGF-I_SDS in the GH^RID group was -0.75 ± 1.0 at 3 months (P = 0.003) and -0.72 ± 1.2 at 1 year compared with the GH^UID group (0.15 ± 1.2; P = 0.005) and GH^FIX group (0.05 ± 1.0; P = 0.02).

Conclusions: Channel parallel growth (i.e., normal height velocity) and IGF-ISDS levels within ± 2 were maintained after completed CUG using a 50% lower individualized dose than that used during the CUG period.

Scope Ingestion of rye bread leads to lower postprandial plasma insulin concentrations than wheat bread ingestion, but most often not too different glucose profiles. The mechanism behind this discrepancy is still largely unknown. This study investigates whether glucose kinetics may explain the observed discrepancy. Methods and results Nine healthy men participated in a crossover study, eating 50 g of available carbohydrates as either refined wheat (WB) or traditional wholemeal rye bread (WMR) during d-[6,6-H-2(2)]glucose infusion. Labeled glucose enrichment is measured by an HPLC-TOF-MS method. The calculated rate of glucose appearance (RaE) is significantly lower after ingestion of WMR during the initial 15 min postprandial period. Additionally, the 0-90 min RaE area under the curve (AUC) is significantly lower after ingestion of WMR, as is plasma gastric inhibitory polypeptide (GIP) at 60 and 90 min. Postprandial glycemic responses do not differ between the breads. Postprandial insulin is lower after ingestion of WMR at 45 and 60 min, as is the 0-90 min AUC. Conclusion Ingestion of WMR elicits a lower rate of glucose appearance into the bloodstream compared with WB. This may explain the lower insulin response observed after rye bread ingestion, commonly known as the rye factor.