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- Allen, David B, et al.
(författare)
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GH Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults.
- 2016
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 174:2, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human growth hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety including; cancer risk, impact on glucose homeostasis and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk and the need for longterm surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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| 5. |
- Beardsall, Kathryn, et al.
(författare)
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Insulin and carbohydrate metabolism
- 2008
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Ingår i: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. - : Elsevier BV. - 1521-690X .- 1532-1908. ; 22:1, s. 41-55
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Forskningsöversikt (refereegranskat)abstract
- Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by glucose delivery from the mother during pregnancy. Maternal hyperglycaemia and gestational diabetes (GDM) are known to be detrimental to offspring, although defining the criteria for diagnosis of GDM is controversial. Recent data suggest that the risk of poor fetal outcome appears to be a continuous variable across the range of glucose control, and that the level of maternal blood glucose for a diagnosis of gestational diabetes needs to be reviewed. After birth, rapid adaptation is necessary for infants to be able to maintain independent glucose homeostasis. This adaptation is compromised in infants who are small for gestational age (SGA), premature, or large for gestational age (LGA). Interestingly, the infants who are born at the extremes of birth weight are also at increased risk of impaired glucose tolerance and diabetes in later life.
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| 6. |
- Ekelund, Ulf, et al.
(författare)
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Association of weight gain in infancy and early childhood with metabolic risk in young adults
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:1, s. 98-103
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Early postnatal life has been suggested as an important window during which risks for long-term health may be influenced. OBJECTIVE: The aim of this study was to examine the independent associations between weight gain during infancy (0-6 months) and early childhood (3-6 yr) with components of the metabolic syndrome in young adults. DESIGN: This was a prospective cohort study (The Stockholm Weight Development Study). SETTING: The study was conducted in a general community. PARTICIPANTS: Subjects included 128 (54 males) singletons, followed from birth to 17 yr. MAIN OUTCOME MEASURE: None of these young adults met the full criteria for the metabolic syndrome. We therefore calculated a continuous clustered metabolic risk score by averaging the standardized values of the following components: waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, glucose, and insulin level. RESULTS: Clustered metabolic risk at age 17 yr was predicted by weight gain during infancy (standardized beta = 0.16; P < 0.0001) but not during early childhood (standardized beta = 0.10; P = 0.23), adjusted for birth weight, gestational age, current height, maternal fat mass, and socioeconomic status at age 17 yr. Further adjustment for current fat mass and weight gain during childhood did not alter the significant association between infancy weight gain with the metabolic risk score (standardized beta = 0.20; P = 0.007). CONCLUSIONS: Rapid weight gain during infancy (0-6 months) but not during early childhood (3-6 yr) predicted clustered metabolic risk at age 17 yr. Early interventions to moderate rapid weight gain even at very young ages may help to reduce adult cardiovascular disease risks.
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| 7. |
- Horsch, S., et al.
(författare)
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Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury
- 2020
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this post-hoc analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants. Methods: This report is an exploratory post-hoc analysis of a phase II trial in which infants <28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers. Results: The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II-III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (n = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed. Conclusion: The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start.
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- Jensen, Rikke Beck, et al.
(författare)
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Baseline IGF-I Levels Determine Insulin Secretion and Insulin Sensitivity during the First Year on Growth Hormone Therapy in Children Born Small for Gestational Age. Results from a North European Multicentre Study (NESGAS)
- 2013
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 80:1, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Developmental programming alters growth and metabolic outcome in children born small for gestational age (SGA). We explored insulin and glucose metabolism in SGA children treated with a fixed GH dose over 1 year. Methods: In the North European Small for Gestational Age Study (NESGAS), 110 short SGA children received GH at 67 mu g/kg/day for 1 year. Insulin secretion was assessed by acute insulin response (AIR), insulin sensitivity (IS) by HOMA and disposition index (DI) by insulin secretion adjusted for IS. Results: First-year GH therapy led to increases in height and IGF-I standard deviation score (SDS), and reductions in IS (p < 0.0001). Compensatory increases in AIR (p < 0.0001) were insufficient and resulted in reduced DI (p = 0.032). Children in the highest IGF-I SDS tertile at baseline were the least insulin sensitive at baseline (p = 0.024) and 1 year (p = 0.006). IGF-I responses after 1 year were positively related to AIR (r = 0.30, p = 0.007) and DI (r = 0.29, p = 0.005). Conclusion: In SGA children treated with a high GH dose for 1 year, baseline IGF-I levels were related to IS whilst gains in height and IGF-I responses were associated with insulin secretion. Defining heterogeneity in IGF-I in SGA children may be useful in predicting growth and metabolic response. Copyright (C) 2013 S. Karger AG, Basel
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| 9. |
- Jensen, Rikke Beck, et al.
(författare)
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Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children: the North European SGA Study (NESGAS)
- 2015
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:3, s. 503-507
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during GH therapy, may reflect common genetic variations related to insulin secretion or sensitivity. Method: Combined multiallele single nucleotide polymorphism scores with known associations with insulin sensitivity or insulin secretion were analyzed for their relationships with spontaneous postnatal growth and first-year responses to GH therapy in 96 short SGA children. Results: The insulin sensitivity allele score (GS-InSens) was positively associated with spontaneous postnatal weight gain (regression coefficient [B]: 0.12 SD scores per allele; 95% confidence interval [CI], 0.01-0.23; P = .03) and also in response to GH therapy with first-year height velocity (B: 0.18 cm/y per allele; 95% CI, 0.02-0.35; P = .03) and change in IGF-1 (B: 0.17 SD scores per allele; 95% CI, 0.00-0.32; P = .03). The association with first-year height velocity was independent of reported predictors of response to GH therapy (adjusted P = .04). The insulin secretion allele score (GS-InSec) was positively associated with spontaneous postnatal height gain (B: 0.15; 95% CI, 0.01-0.30; P = .03) and disposition index both before (B: 0.02; 95% CI, 0.00-0.04; P = .04) and after 1 year of GH therapy (B: 0.03; 95% CI, 0.01-0.05; P = .002), but not with growth and IGF-1 responses to GH therapy. Neither of the allele scores was associated with size at birth. Conclusion: Genetic allele scores indicative of insulin sensitivity and insulin secretion were associated with spontaneous postnatal growth and responses to GH therapy in short SGA children. Further pharmacogenetic studies may support the rationale for adjuvant therapies by informing the mechanisms of treatment response.
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| 10. |
- Kimani-Murage, Elizabeth W., et al.
(författare)
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Nutritional status and HIV in rural South African children
- 2011
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431 .- 1471-2431. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Achieving the Millennium Development Goals that aim to reduce malnutrition and child mortality depends in part on the ability of governments/policymakers to address nutritional status of children in general and those infected or affected by HIV/AIDS in particular. This study describes HIV prevalence in children, patterns of malnutrition by HIV status and determinants of nutritional status.Methods: The study involved 671 children aged 12-59 months living in the Agincourt sub-district, rural South Africa in 2007. Anthropometric measurements were taken and HIV testing with disclosure was done using two rapid tests. Z-scores were generated using WHO 2006 standards as indicators of nutritional status. Linear and logistic regression analyses were conducted to establish the determinants of child nutritonal status.Results: Prevalence of malnutrition, particularly stunting (18%), was high in the overall sample of children. HIV prevalence in this age group was 4.4% (95% CI: 2.79 to 5.97). HIV positive children had significantly poorer nutritional outcomes than their HIV negative counterparts. Besides HIV status, other significant determinants of nutritional outcomes included age of the child, birth weight, maternal age, age of household head, and area of residence.Conclusions: This study documents poor nutritional status among children aged 12-59 months in rural South Africa. HIV is an independent modifiable risk factor for poor nutritional outcomes and makes a significant contribution to nutritional outcomes at the individual level. Early paediatric HIV testing of exposed or at risk children, followed by appropriate health care for infected children, may improve their nutritional status and survival.
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