RESUMO
BACKGROUND: Growth retardation is one of the main hallmarks of CHARGE syndrome (CS), yet little is known about the body proportions of these children. Knowledge of body proportions in CS may contribute to a better characterization of this syndrome. This knowledge is important when considering starting growth-stimulating therapy. METHODS: For this cross-sectional study, we selected 32 children with CS and a CHD7 mutation at the Dutch CHARGE Family Day in 2016 or 2017 and the International CHARGE conference in Orlando, Florida, in 2017. We used photogrammetric anthropometry-a measurement method based on digital photographs-to determine various body proportions. We compared these to measurements in 21 normally proportioned children with growth hormone deficiency, using independent-samples t test, Mann-Whitney U test, or chi-square test as appropriate. RESULTS: Children with CS appear to have a shorter trunk in proportion to their height, head length, and arm length. Children with CS also had smaller feet proportional to tibia length compared to controls. The change of body proportions with age was similar in children with CS and controls. CONCLUSION: Body proportions in children with CS are significantly different from those of normally proportioned controls, but a similar change of body proportions with age was noted for both groups.
Assuntos
Antropometria/métodos , Síndrome CHARGE/diagnóstico , Fotogrametria/métodos , Adolescente , Antropometria/instrumentação , Estatura , Síndrome CHARGE/genética , Síndrome CHARGE/patologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Cabeça/anormalidades , Humanos , Masculino , Fotogrametria/instrumentação , Tronco/anormalidadesRESUMO
PURPOSE: The effects of growth hormone (GH) treatment on linear growth and body composition have been studied extensively. Little is known about the GH effect on energy expenditure (EE). The aim of this study was to investigate the effects of GH treatment on EE in children, and to study whether the changes in EE can predict the height gain after 1 year. METHODS: Total EE (TEE), basal metabolic rate (BMR), and physical activity level (PAL) measurements before and after 6 weeks of GH treatment were performed in 18 prepubertal children (5 girls, 13 boys) born small for gestational age (n = 14) or with growth hormone deficiency (n = 4) who were eligible for GH treatment. TEE was measured with the doubly labelled water method, BMR was measured with an open-circuit ventilated hood system, PAL was assessed using an accelerometer for movement registration and calculated (PAL = TEE/BMR), activity related EE (AEE) was calculated [AEE = (0.9 × TEE) - BMR]. Height measurements at start and after 1 year of GH treatment were analysed. This is a 1-year longitudinal intervention study, without a control group for comparison. RESULTS: BMR and TEE increased significantly (resp. 5% and 7%). Physical activity (counts/day), PAL, and AEE did not change. 11 out of 13 patients (85%) with an increased TEE after 6 weeks of GH treatment had a good first-year growth response (∆height SDS > 0.5). CONCLUSIONS: GH treatment showed a positive effect on EE in prepubertal children after 6 weeks. No effect on physical activity was observed. The increase in TEE appeared to be valuable for the prediction of good first-year growth responders to GH treatment.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/farmacologia , Metabolismo Basal/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Índice de Massa Corporal , Criança , Pré-Escolar , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Feminino , Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Resultado do TratamentoRESUMO
Facial characteristics, short stature, and skeletal anomalies have been described for the clinical diagnosis of Kabuki Syndrome (KS) in children. However, no studies have investigated body proportions in KS. Knowledge of body proportions in KS may contribute to better insight into the growth pattern and characterization of this genetic disorder. Therefore we compared body proportions of children with KS to normally proportioned controls to investigate if atypical body proportions are part of this genetic disorder. This study was designed and conducted within the setting of the Maastricht University Medical Centre (MUMC+), the official Dutch expert center for Kabuki syndrome. We conducted a cross-sectional study in 32 children (11 children with KS and 21 controls). Body proportions were determined by means of photogrammetric anthropometry, measurements based on digital photography. Body proportions, quantified as body ratios, differ significantly in children with KS from normally proportioned children. Children with KS have larger heads and longer arms proportional to their trunks and have been found to have longer upper arms proportional to their tibia length and feet. Based on deviations in body proportions it was shown possible to discern children with KS from normally proportioned controls.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Constituição Corporal/genética , Proteínas de Ligação a DNA/genética , Face/anormalidades , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/genética , Proteínas de Neoplasias/genética , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/genética , Anormalidades Múltiplas/fisiopatologia , Antropometria , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Face/fisiopatologia , Feminino , Expressão Gênica , Doenças Hematológicas/fisiopatologia , Humanos , Masculino , Mutação , Doenças Vestibulares/fisiopatologiaRESUMO
OBJECTIVE: To test the hypothesis that the inverse association between infant growth and endothelial function at 6 months would persist to 24 months and that accelerated growth would lead to an increased percent body fat, which would, in turn, impact negatively on endothelial function. STUDY DESIGN: In a prospective observational study, 104 healthy term newborns underwent anthropometry and measurements of vascular vasodilation at 0, 6, 12, and 24 months. We recorded maximum vasodilation in response to acetylcholine (endothelium-dependent) and nitroprusside (endothelium-independent) by use of laser-Doppler vascular perfusion monitoring of the forearm skin vasculature. Additional anthropometry at 1 and 3 months was collected from child welfare centers. The data were analyzed by multilevel linear regression. RESULTS: Weight gain from 0-1 month was associated inversely with maximum perfusion in response to acetylcholine at the age of 2 years (b = -8.28 perfusion units [PU] per Δ z-score, P = .03). Weight gain from 0-1 month was related positively to maximum perfusion in response to nitroprusside (b = 10.12 PU per Δ z-score, P = .04), as was birth weight (b = 8.02 PU per z-score, P = .02). Body fat percentage did not have a significant effect in any of the perfusion models and was not related to maximum perfusion at 2 years. CONCLUSION: Infant weight gain from 0-1 month is inversely related to endothelial function in healthy term infants, at least to the age of 2 years. This relationship was not explained by an increased percentage body fat.
Assuntos
Peso ao Nascer/fisiologia , Desenvolvimento Infantil/fisiologia , Endotélio Vascular/fisiologia , Vasodilatação/fisiologia , Aumento de Peso/fisiologia , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Valores de ReferênciaRESUMO
The current local overweight-prevention protocols are not applied as intended by Dutch child healthcare physicians and nurses. The development of a training program for these practitioners, based on the Intervention Mapping framework, with the aim of improving overweight-prevention in a child's first year, is described in this study. The needs assessment showed three program objectives to be relevant, namely improving: (i) awareness of the importance of early overweight-prevention; (ii) the competence to discuss (the risk of) overweight with parents; and (iii) working systematically according to the overweight-prevention protocol. A matrix was then created specifying the program objectives in terms of personal learning objectives and environmental change objectives, and appropriate strategies were identified. The results suggested that a more active tailored and structured change strategy improves knowledge and skills, in particular, which results in a better overall implementation of the overweight-prevention protocol. This training program should help providers understand how the implementation of a protocol, such as the overweight-prevention protocol, can be improved. Using the Intervention Mapping framework for systematic protocol implementation seems a valuable option.
Assuntos
Promoção da Saúde/organização & administração , Sobrepeso/prevenção & controle , Obesidade Infantil/prevenção & controle , Serviços Preventivos de Saúde/organização & administração , Pré-Escolar , Educação Médica Continuada/organização & administração , Educação Continuada em Enfermagem/organização & administração , Feminino , Humanos , Lactente , Masculino , Países Baixos , Pais/educação , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Medição de RiscoRESUMO
OBJECTIVE: To identify determinants of growth during infancy. STUDY DESIGN: The sample included 424 twin pairs from the East Flanders Prospective Twin Survey. Multilevel regression analysis was performed and intrapair growth correlations were calculated. The main outcome measure was growth, measured in g/kg/d (0-1 month) or in change in weight z-score (0-6, 6-12 and 12-24 months). RESULTS: Growth during infancy was associated with birth weight and gestational age. One z-score increase in birth weight resulted in -1.77 g/kg/d less growth from 0-1 month (P < .0001). The effect size decreased with age until -0.02 (P = .70) z-scores less growth from 12 to 24 months. Corresponding numbers for one z-score increase in gestational age decreased from 0.78 (P = .001) to 0.06 (P = .40). From 12 to 24 months, paternal height had a significant positive effect. The difference in growth similarity within the twin pair between monozygotic and dizygotic twins increased from non-significant from 0 to 1 month (P = .49) to a monozygotic:dizygotic ratio approximating 2:1 from 12 to 24 months (P = .002). CONCLUSION: From 0 to 1 month, environmental factors are most important for growth, whereas genetic factors become more important over time. This is a first step in identifying age windows for future counseling and interventions on the effects of accelerated growth.
Assuntos
Gêmeos Dizigóticos/fisiologia , Gêmeos Monozigóticos/fisiologia , Peso ao Nascer/fisiologia , Estatura , Diabetes Gestacional/fisiopatologia , Pai , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Análise Multivariada , GravidezRESUMO
INTRODUCTION: Kabuki syndrome (KS) is a genetic disorder with characteristic facial dysmorphisms, short stature, hypertension, and obesity later in life. The aim of this study was to evaluate catch-up growth and cardiovascular markers before and during growth hormone (rhGH) treatment in KS children. METHODS: This prospective study included 18 children whose KS was genetically established. Each KS subject received rhGH for a period of 2 years. Several measurements were performed before and during treatment: anthropometry, glucose metabolism, lipid profile, markers for endothelial function, and low-grade inflammation. RESULTS: This study found an increase in delta height standard deviation score (SDS) for the whole group of 1.1 SDS after 2 years of rhGH treatment. Baseline metabolic profiles showed no cardiometabolic abnormalities in these children. Although 4 out of 18 children were obese, there were no signs of the metabolic syndrome. During rhGH treatment, serum low-density lipoprotein cholesterol concentrations decreased significantly (2.16-1.91 mmol/L, p = 0.04). Apolipoprotein B100 concentrations also showed a reduction after 24 months of treatment, but the other lipid and (apo)lipoprotein parameters did not change. While other endothelial function markers were stable, only vascular cell-adhesion molecule-1 concentrations increased (1,084-1,161 pg/mL, p < 0.01) during rhGH therapy. Furthermore, BMI and waist circumference improved during treatment. There were no signs of hypertension. CONCLUSIONS: At baseline and during rhGH therapy, there were no signs of the metabolic syndrome. This is the first study demonstrating that rhGH treatment in KS children is a safe and effective therapy and that it positively influences linear height without exerting adverse effects on a wide array of cardiovascular risk markers.
Assuntos
Anormalidades Múltiplas/tratamento farmacológico , Estatura/efeitos dos fármacos , Face/anormalidades , Doenças Hematológicas/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/farmacologia , Obesidade/tratamento farmacológico , Doenças Vestibulares/tratamento farmacológico , Anormalidades Múltiplas/genética , Seguimentos , Doenças Hematológicas/genética , Hormônio do Crescimento Humano/deficiência , Humanos , Síndrome Metabólica , Estudos Prospectivos , Doenças Vestibulares/genética , Circunferência da CinturaRESUMO
Previous studies demonstrated that hyperglycemic glucose concentrations are observed in children that are overweight or have obesity. The aim of this study was to evaluate the effect of a 12 month lifestyle intervention on free-living glycemic profiles in children that were overweight or had obesity, and the association of the alterations with changes in cardiovascular risk parameters. BMI z-score, free-living glycemic profiles, continuous overlapping net glycemic action (CONGA), and cardiovascular parameters were evaluated before and after a multidisciplinary lifestyle intervention, in 33 non-diabetic children that were overweight or had obesity. In children with a decrease in BMI z-score, the duration which glucose concentrations were above the high-normal threshold (6.7 mmol/L) and the glycemic variability decreased significantly. In these children, a decrease in median sensor glucose was associated with decreases in LDL-cholesterol, and systolic and diastolic blood pressure z-score. A decrease in BMI z-score was associated with a decrease in CONGA1, 2, and 4. In conclusion, the glycemic profiles in free-living conditions in children that were overweight improved in children with a decrease in BMI z-score after lifestyle intervention. In those children, changes in median sensor glucose concentrations were associated with changes in LDL-cholesterol and blood pressure z-scores. These results suggest that glucose homeostasis can improve after one year of lifestyle intervention and that these improvements are associated with improvements in cardiovascular health parameters.
Assuntos
Glicemia , Estilo de Vida Saudável/fisiologia , Obesidade Infantil/sangue , Obesidade Infantil/reabilitação , Pressão Sanguínea , Índice de Massa Corporal , Criança , LDL-Colesterol/sangue , Exercício Físico , Comportamento Alimentar , Feminino , Fatores de Risco de Doenças Cardíacas , Homeostase , Humanos , Hiperglicemia/sangue , Hiperglicemia/etiologia , Masculino , Obesidade Infantil/psicologia , Prognóstico , Fatores de TempoRESUMO
Although the current use of growth hormone (GH) stimulation tests (GHSTs) is still subject to debate, the tests are widely used to diagnose GH deficiency. This literature review evaluates primarily the sensitivity, specificity and reliability of GHSTs and secondarily their convenience. Single pharmacological tests typically address only a single pathway in the complex physiological regulation of GH secretion and are therefore characterized by lower sensitivity, specificity and reliability than combined pharmacological tests or physiological tests. In spite of the high levels of sensitivity, specificity and reliability, physiological tests require considerably more effort to perform, from the physician as well as from the child. Therefore, a need for an alternative, convenient, physiological GHST still remains. Oral ingestion of dietary protein is convenient in practice and may induce more physiological stimulation of GH secretion, hence may be a promising valuable addition to the existing GHSTs in GH deficiency.
Assuntos
Nanismo Hipofisário/diagnóstico , Hormônio do Crescimento/sangue , Hormônio do Crescimento/deficiência , Adolescente , Arginina , Criança , Pré-Escolar , Quimioterapia Combinada , Nanismo Hipofisário/tratamento farmacológico , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , SonoRESUMO
OBJECTIVE: To evaluate the effect of end-stage pediatric liver disease and liver transplantation on growth and final height. PATIENTS AND METHODS: We evaluated growth at 2 years (n = 101) and 5 years (n = 63) after pediatric liver transplantation (LTx). Twenty-three children reached final height. Height was expressed as a standard deviation score of the target height (zTH score) of each patient. RESULTS: At the first 2 years after LTx, the zTH score was significantly increased from -1.7 to -1.3 SD (P < 0.05). Growth at 2 or 5 years after LTx, expressed as DeltazTH score, was positively correlated with pretransplant growth retardation (P < 0.05). In comparison with patients with noncholestatic primary liver disease, patients with cholestatic primary liver disease were more severely growth retarded before LTx (zTH score -2.0 vs -1.2 SD, P < 0.05) and had better growth in the first 2 years after LTx (DeltazTH score +0.6 vs -0.1 SD, P < 0.05). Twelve of the 23 patients had a final height below -1.3 SD of their target height. CONCLUSIONS: Growth retardation is common in children before LTx, particularly in children with an underlying cholestatic disease. After LTx, catch-up growth was partial and was prominent only in cholestatic children who had been severely growth retarded before LTx. After LTx during childhood, approximately 50% of patients reach a final height lower than -1.3 SD of their genetic potential.
Assuntos
Estatura/fisiologia , Transtornos do Crescimento/epidemiologia , Crescimento/fisiologia , Transplante de Fígado , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Terapia de Imunossupressão , Lactente , Recém-Nascido , Hepatopatias/cirurgia , Hepatopatias/terapia , Masculino , Fatores de TempoRESUMO
Context: Overweight and obese children have an increased risk to develop cardiovascular diseases (CVDs) in which thyroid-stimulating hormone (TSH) has been suggested as an intermediary factor. However, results of cross-sectional studies are inconclusive, and intervention studies investigating changes in TSH concentrations in association with changes in cardiovascular risk parameters in overweight and obese children are scarce. Objective: To gain insight in associations of circulating TSH concentrations and cardiovascular risk parameters in overweight and obese children. Design: Nonrandomized lifestyle intervention. Setting: Centre for Overweight Adolescent and Children's Healthcare. Patients: Three hundred thirty euthyroid overweight and obese children. Intervention: Long-term lifestyle intervention. Main Outcome Measures: TSH concentrations, pituitary TSH release in response to thyrotropin-releasing hormone (TRH), and cardiovascular risk parameters. Results: At baseline, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG), and monocyte chemotactic protein 1 concentrations were significantly associated with serum TSH concentrations. TSH release by the pituitary in response to exogenous TRH was not associated with cardiovascular risk parameters. During lifestyle intervention, several cardiovascular risk parameters significantly improved. In children whose body mass index z score improved, changes in TSH concentrations were significantly associated with changes in TC, LDL-C, and TAG concentrations. Conclusions: In euthyroid overweight and obese children, circulating TSH concentrations are positively associated with markers representing increased CVD risk. Changes in TSH concentrations are also associated with changes in lipid concentrations in children with successful weight loss, which is consistent with TSH being an intermediary factor in modulating lipid and lipoprotein metabolism.
Assuntos
Doenças Cardiovasculares/epidemiologia , Estilo de Vida , Obesidade Infantil/terapia , Tireotropina/metabolismo , Programas de Redução de Peso , Adolescente , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Quimiocina CCL2/metabolismo , Criança , Pré-Escolar , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Feminino , Humanos , Insulina/metabolismo , Resistência à Insulina , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Sobrepeso/metabolismo , Sobrepeso/terapia , Obesidade Infantil/metabolismo , Risco , Triglicerídeos/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.
Assuntos
Obesidade/sangue , Hipófise/metabolismo , Hormônio Liberador de Tireotropina/farmacologia , Tireotropina/sangue , Adolescente , Criança , Estudos Transversais , HumanosRESUMO
Insulin resistance is common among children with overweight and obesity. However, knowledge about glucose fluctuations in these children is scarce. This study aims to evaluate glycaemic profiles in children with overweight and obesity in free-living conditions, and to examine the association between glycaemic profiles with insulin resistance and cardiovascular risk parameters. One hundred eleven children with overweight and obesity were included. 48-hour sensor glucose concentrations in free-living conditions, fasting plasma and post-glucose load concentrations, serum lipid and lipoprotein concentrations, homeostatic model assessment of insulin resistance (HOMA-IR), and blood pressure were evaluated. Hyperglycaemic glucose excursions (≥7.8 mmol/L) were observed in 25% (n = 28) of the children. The median sensor glucose concentration was 5.0 (2.7-7.3) mmol/L, and correlated with fasting plasma glucose concentrations (rs = 0.190, p = 0.046), serum insulin concentrations (rs = 0.218, p = 0.021), and HOMA-IR (rs = 0.230, p = 0.015). The hyperglycaemic area under the curve (AUC) correlated with waist circumference z-score (rs = 0.455, p = 0.025), triacylglycerol concentrations (rs = 0.425, p = 0.024), and HOMA-IR (rs = 0.616, p < 0.001). In conclusion, hyperglycaemic glucose excursions are frequently observed in children with overweight and obesity in free-living conditions. Children with insulin resistance had higher median sensor glucose concentrations and a larger hyperglycaemic sensor glucose AUC, which are both associated with specific parameters predicting cardiovascular disease risk.
Assuntos
Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Resistência à Insulina , Lipídeos/sangue , Obesidade/sangue , Adolescente , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Criança , Feminino , Humanos , Masculino , Obesidade/complicações , Obesidade/fisiopatologia , Fatores de RiscoRESUMO
BACKGROUND: Taking multiple anthropometric measurements for the description of body proportions in an accurate way is a time-consuming procedure that requires specific tools and skills. This is why we developed an alternative method based on digital photography for taking these measurements which is faster and easier to use, to make anthropometry more user-friendly and approachable to paediatricians. METHODS: We conducted a cross-sectional study in 54 children between 2 and 18 years of age. We compared manual measurements with photogrammetric measurements to validate our method. RESULTS: Inter-observer correlations of all measurements are ≥0.96 and mean differences are 0.3-0.9 cm, except for arm span. Comparison of manual to photogrammetric measurements shows mean differences of 0.6-1.3 cm, with correlations ≥0.92, except for sitting height and arm span. Correlations of ratios between methods are height/sitting height (r=0.77), biacromium/biiliacum (r=0.74) and subischial leg length/sitting height (r=0.75). CONCLUSION: Photogrammetric anthropometry is faster, easier to use and provides the paediatrician with more flexibility as taking the digital photographs and performing the analysis are separated.
Assuntos
Antropometria/métodos , Estatura/fisiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , SoftwareRESUMO
The objective of this study was to investigate whether short-term changes in metabolism, as a result of GH therapy, could be used to predict its growth effect after 1 yr. Twenty-eight children (8.7 +/- 2.8 yr) were selected, based on anthropometric criteria characterizing GH-deficient patients. In addition, 21 healthy, age- and sex-matched controls (8.9 +/- 3.1 yr) were included. Total body water (TBW) and height were measured before and at 6 wk and 1 yr after the start of treatment. After 1 yr of treatment, patients were divided into good and poor responders, based on a change in height of at least 0.7 SD. Because individuals of different heights were compared, changes in TBW after 6 wk were corrected for height(2), in accordance with the body mass index. Eighty percent of the children who showed a good response to GH therapy had a change in TBW divided by height(2) exceeding the 2 SD reference line of the controls. In contrast, poor responders did not differ from controls. Maximum GH concentrations found during endocrine tests were not significantly different between good and poor responders. Changes in body composition data, after 6 wk, proved valuable in identifying good responders to GH therapy.
Assuntos
Composição Corporal/efeitos dos fármacos , Hormônio do Crescimento/uso terapêutico , Crescimento/efeitos dos fármacos , Hormônio do Crescimento Humano/deficiência , Estatura/efeitos dos fármacos , Água Corporal/metabolismo , Criança , Feminino , Humanos , Masculino , Erros Inatos do Metabolismo/tratamento farmacológico , Prognóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m(2).d; approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter 6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6 IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized 17beta-estradiol was given orally. After a mean duration of GH treatment of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or -0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, -1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than -2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV.
Assuntos
Estatura/efeitos dos fármacos , Estradiol/administração & dosagem , Hormônio do Crescimento Humano/administração & dosagem , Síndrome de Turner/tratamento farmacológico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Estradiol/efeitos adversos , Feminino , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Fator de Crescimento Insulin-Like I/análise , Síndrome de Turner/fisiopatologiaRESUMO
BACKGROUND/AIMS: To investigate whether short-term changes in body composition as a result of growth hormone therapy could be used to predict its growth effect after 1 year in children with growth hormone deficiency (GHD) and children born small for gestational age (SGA). METHODS: 88 GHD children and 99 SGA children who started treatment with recombinant human growth hormone were included. Total body water (TBW) and height were measured. After 1 year, patients were divided into adequate and inadequate responders. RESULTS: In GHD and SGA children a sensitivity of 87 and 53%, respectively, and a specificity of 58 and 83%, respectively, were found. The positive predictive values for GHD and SGA children were 73 and 90%, respectively. The negative predictive values were 75 and 32%, respectively. CONCLUSION: Changes in body composition data measured by TBW are a valuable tool to correctly predict 75% of the GHD children and are only useful in SGA children when the change in TBW is above the cut-off value of 0.7 l/m(2).
Assuntos
Biomarcadores Farmacológicos , Água Corporal/efeitos dos fármacos , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/metabolismo , Água Corporal/metabolismo , Água Corporal/fisiologia , Criança , Pré-Escolar , Deutério , Seguimentos , Transtornos do Crescimento/metabolismo , Hormônio do Crescimento Humano/deficiência , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Valor Preditivo dos Testes , Prognóstico , Resultado do TratamentoRESUMO
Low birth weight and accelerated infant growth are associated with cardiovascular disease in adulthood. Endothelial dysfunction is regarded as a precursor of atherosclerosis and is also related to infant growth. We aimed to examine whether an association between infant growth and endothelial function is already present during discrete periods of growth during the first 6 months of life in healthy term infants. A cohort of 104 newborns was studied in the first week after birth and reexamined at the age of 6 months. Maximum vasodilatation in response to acetylcholine (endothelium dependent) and nitroprusside (endothelium independent) was measured in the vasculature of the forearm skin, using laser Doppler flowmetry and iontophoresis. Growth was calculated as difference in Z scores for weight, length, weight-for-length, and head circumference. Multivariable multilevel linear regression was used for the analysis. Growth from 0 to 1 month (calculated as difference in weight) was the only window in the first 6 months of life that was significantly and inversely associated with endothelium-dependent vasodilatation at 6 months (b=-11.72 perfusion units per Z score, P=0.01 in multivariable analysis). Birth size was not important when considered simultaneously with infant growth. Maximum endothelium-independent vasodilatation was not associated with birth size or growth parameters. We conclude that growth in the first month of life is inversely associated with endothelium-dependent vasodilatation at the age of 6 months in healthy term infants, regardless of birth size.
Assuntos
Peso ao Nascer/fisiologia , Peso Corporal/fisiologia , Endotélio Vascular/fisiologia , Vasodilatação/fisiologia , Acetilcolina/farmacologia , Estudos de Coortes , Fatores Relaxantes Dependentes do Endotélio/farmacologia , Antebraço , Humanos , Lactente , Recém-Nascido , Iontoforese , Fluxometria por Laser-Doppler , Modelos Lineares , Análise Multivariada , Nitroprussiato/farmacologia , Pele/irrigação sanguínea , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
OBJECTIVE: The fetal response to an adverse intrauterine environment - reflected in low birth weight - is thought to cause an increased risk for adult hypertension. A possible mechanism by which fetal adaptive responses contribute to hypertension is an adverse effect on endothelial function. Identifying individuals with endothelial dysfunction as early as possible may assist in understanding the inverse association between birth weight and hypertension. The present study aimed to identify determinants of endothelial vasodilatation in the first week of life. METHODS: One hundred and four term newborns were studied in the first week after birth with regard to maximum vasodilatation in response to acetylcholine (endothelium-dependent) and nitroprusside (endothelium-independent) in the vasculature of the forearm skin, by use of a laser-Doppler device and iontophoresis. Bivariable and multivariable linear regression with various familial, gestational and neonatal potential covariates were used for the analysis. RESULTS: In the bivariable analysis, maximum perfusion after administration of acetylcholine was positively associated with birth weight, length, head circumference and maternal education level, but negatively associated with maternal hypertension during pregnancy. In the multivariable analysis, head circumference [bâ=â11.9 perfusion units/z-score, Pâ=â0.02] and hypertension during pregnancy (bâ=â-25.3 perfusion units from nonhypertensive to hypertensive, Pâ=â0.02) remained significantly associated. Maximum perfusion after administration of nitroprusside was not related to any of the anthropometric measures; it was, however, related to gestational age (bâ=â-11.1 perfusion units/week, Pâ=â0.009). CONCLUSION: This study showed that body size, head circumference in particular, is positively associated with endothelial vasodilatation in newborns, whereas hypertension during pregnancy is inversely associated with endothelial vasodilatation.
Assuntos
Tamanho Corporal , Endotélio Vascular/fisiopatologia , Hipertensão/fisiopatologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Vasodilatação , Feminino , Humanos , Hipertensão/complicações , Recém-Nascido , GravidezRESUMO
Decreased height and weight in treated children with classical galactosemia have been reported. However, growth has not been extensively studied. Patients might be at risk for an abnormal growth because of either disease-related intrinsic factors or diet-related factors. The objective was to gain insight in growth in treated children and adolescents with classical galactosemia. The studied population was a previously reported group of 40 classical galactosemia children. Prenatal growth was evaluated using length, weight and head circumference (HC) data from welfare centers or parents. Postnatal growth was evaluated using three height and weight measurements at baseline, 1 and 2 years to calculate growth velocities. Height Z-score was also corrected for target height Z-score (height Z-score divided by target height Z-score). Linear regression analysis was performed between growth velocities, IGF-I, IGFBP-3, dietary intake and galactose-1-phosphate-uridyltransferase activity. We found normal length (median 50.5 cm), weight (median 3,255 grams) and HC (median 33.9 cm) at birth. Mean height growth velocity was 0.87+/-1.2 for boys and -0.89+/-2.1 for girls, and mean weight growth velocity was 0.91+/-1.6 for boys and -0.74+/-1.3 for girls. Mean height corrected for target height was -1.5+/-0.9 in girls and -0.6+/-0.7 in boys. Height growth velocity was correlated with IGF-I (Pearson correlation= 0.499), IGFBP-3 (Pearson correlation 0.4) and height Z-scores corrected for target height Z-scores (Pearson correlation=0.550). Five children grew beyond the age of 18 years. In conclusion, prenatal growth was normal but postnatal growth was affected. Predicted final height is less than target height in most patients; however, target height might be reached for the children who grow beyond the age of 18. Decreased IGF-I and IGFBP-3 and or suboptimal hormonal replacement in girls might play a role.