[Not Available]. / Valores de normalidad de índice de masa corporal y perímetro abdominal en población española desde el nacimiento a los 28 años de edad.

Introducción: saber diagnosticar y tratar la obesidad se ha convertido en el mayor reto del siglo XXI, debido al aumento de su prevalencia.Objetivos: determinar los valores de normalidad de perímetro abdominal (PA) e índice de masa corporal (IMC) según edad y sexo en población española sana.Métodos: estudio longitudinal observacional realizado entre 1980 y 2014. Se incluyeron 165 niños y 169 niñas recién nacidas, recogiendo datos de forma anual hasta los 18 años (74 varones y 92 mujeres), y posteriormente a los 28 años (42 varones y 45 mujeres). Se realizó medición de peso, longitud/talla y perímetro abdominal. Se calcularon los percentiles (P3, P10, P25, P50, P75, P90, P97) de IMC y PA según edad y sexo.Resultados: se presentan datos evolutivos de IMC y PA durante la infancia, destacando cómo aumentan los valores entre los 18 y 28 años de los percentiles superiores al p50, sobre todo en mujeres. Existe una correlación positiva en relación al PA entre el valor obtenido a los 3 años con el valor de los 18 años y de los 28 años tanto en varones (r = 0,722 y r = 0,605, p = 0,000, respectivamente) como en mujeres(r = 0,922, r = 0,857, p = 0,000, respectivamente). Y entre los 18 y 28 años (r = 0,731, p = 0,000 para varones y r = 0,961, p = 0,000 para mujeres).Conclusión: se presentan valores de normalidad de PA e IMC según edad y sexo, que podrán utilizarse como herramienta de referencia para identificar a personas con riesgo de desarrollar enfermedades cardiovasculares o diabetes.

Sitting height/standing height ratio in a Spanish population from birth to adulthood.

INTRODUCTION: For the diagnosis of patients with growth disorders, visual inspection and the measurement of body segments may provide important information. The most commonly used method is the assessment of the sitting/standing height (SH/SH) ratio and its comparison to aged matched controls. OBJECTIVE: To establish the normal values of the sitting/standing height ratio in a normal Aragonese population from birth to 18 years old. POPULATION AND METHODS: Longitudinal study from birth to 18 years old. Length (up to 3 years old), standing height (as of 2 years old) and sit-ting height were recorded. Percentiles for sitting/ standing height ratio were determined. RESULTS: The study included 165 male children and 167 female children. The values of the sitting/standing height ratio decrease from birth both in males and females (0.656 and 0.647, respectively) until the onset of puberty (0.514 and 0.519); and later start to slightly increase until reaching the definitive adult ratio (0.52 and 0.53, respectively). CONCLUSION: Sitting/standing height ratio values are presented in normal male and female children up to 18 years old. This ratio decreases from birth to puberty and then slightly increases until reaching the final adult ratio.

Relación talla sentada/talla de pie del nacimiento a la adultez en niños españoles / Sitting height/standing height ratio in a spanish population from birth to adulthood

Introducción. Para el diagnóstico de los pacientes con trastornos del crecimiento, la inspección visual y la medida de los segmentos corporales pueden proporcionar una importante información. El método más utilizado es la evaluación de la relación entre la talla sentada y la talla de pie (TS/TP) y su comparación con los referentes según la edad. Objetivo. Determinar los valores de normalidad de la relación talla sentada/talla de pie en una población normal aragonesa, desde el nacimiento hasta los 18 años. Población y métodos. Estudio longitudinal desde el nacimiento hasta los 18 años. Se registró la longitud (hasta los 3 años), la talla de pie vertical (desde los 2 años) y la talla sentada. Se determinaron los percentiles de la relación talla sentada/talla de pie. Resultados. Se incluyeron 165 varones y 167 mujeres. La relación talla sentada/talla de pie desciende desde el nacimiento en los niños y las niñas (0,656 y 0,647 respectivamente) hasta el inicio de la pubertad (0,514 y 0,519); más tarde aumenta levemente hasta alcanzar la relación defnitiva del adulto (0,52 y 0,53). Conclusión. Se presentan los valores de la relación talla sentada/talla de pie, en niños y niñas normales, hasta los 18 años. Esta relación disminuye desde el nacimiento hasta la pubertad y luego aumenta levemente hasta alcanzar la relación defnitiva del adulto.

Introduction. For the diagnosis of patients with growth disorders, visual inspection and the measurement of body segments may provide important information. The most commonly used method is the assessmentof the sitting/standing height (SH/SH) ratio and its comparison to aged matched controls. Objective. To establish the normal values of the sitting/standing height ratio in a normal Aragonese population from birth to 18 years old. Population and Methods.Longitudinal study from birth to 18 years old. Length (up to 3 years old), standing height (as of 2 years old) and sit-ting height were recorded. Percentiles for sitting/ standing height ratio were determined. Results. The study included 165 male children and 167 female children. The values of the sitting/standing height ratio decrease from birth both in males and females (0.656 and 0.647, respectively) until the onset of puberty (0.514 and 0.519); and later start to slightly increase until reaching the defnitive adult ratio (0.52 and 0.53, respectively). Conclusion. Sitting/standing height ratio values are presented in normal male and female children up to 18 years old. This ratio decreases from birth to puberty and then slightly increases until reaching the fnal adult ratio.

[Carotid intima-media thickness; normal values from 4 years]. / Índice íntima-media carotídeo; valores de normalidad desde los 4 años.

INTRODUCTION: The study of the common carotid artery using ultrasound, ever has greater significance for the prevention, treatment and evaluation of the risk of developing cardiovascular disease. Increased intima-media thickness is associated with the presence of other cardiovascular, cerebrovascular disease and the development of atherosclerosis in both adults and pediatric populations. MATERIAL AND METHODS: A cross-sectional study in 202 healthy children aged between 4 and 15 years. It has been analyzed auxological data, systolic and diastolic blood pressure and carotid intima-media thickness. RESULTS: There are 100 men and 102 women, with no differences among them about sex; it is shown graphical representations of the values of carotid intima-media thickness in the total sample and by gender. There is a positive correlation between carotid intima-media thickness with age (r = 0.229, p < 0.05), weight (r = 0.228, p < 0.05), height (r = 0.265, p > 0.01) and BMI (r = 0.212, p < 0.05). DISCUSSION: Identification of modifiable risk factors should be our priority in clinical practice. Thus, in any health program it should be focused on reducing cardiovascular risk in children and adolescents by promoting a lifestyle of healthy eating and regularly physical exercise. Ultrasound measurement of carotid intima-media thickness is an added factor for an early identification of cardiovascular disease and its evolution in both adult and pediatric population.

Introducción: El estudio de la arteria carotídea común mediante ultrasonidos, cada vez cobra mayor importancia para la prevención, tratamiento y evaluación del riesgo de desarrollar enfermedad cardiovascular. Un aumento del índice íntima-media se asocia con la presencia de otros factores cardiovasculares, enfermedad cardiovascular y cerebrovascular y ateroesclerosis en otras zonas del sistema vascular tanto en adultos como en población pediátrica. Material y métodos: Estudio transversal en 202 niños sanos de edades comprendidas entre 4 y 15 años en los que se han valorado parámetros auxológicos, tensión arterial sistólica y diastólica e índice íntima-media carotídea. Resultados: La muestra se compone de 100 varones y 102 mujeres, sin que existan diferencias entre ellos respecto al sexo; se presentan representaciones gráficas de los valores de índice íntima-media carotídea tanto en el total de la muestra como por sexos; existe una correlación positiva entre el índice íntima-media carotídeo con la edad (r = 0,229, p < 0,05), el peso (r = 0,228, p < 0,05), la talla (r = 0,265, p > 0,01) y el IMC (r = 0,212, p < 0,05). Discusión: La identificación de los factores de riesgo modificables deben ser nuestra prioridad en la práctica clínica diaria. Por ello, en todo programa de salud debe hacerse énfasis en la reducción de riesgo en niños y adolescentes mediante la promoción de un estilo de vida adecuado con alimentación saludable y realización de ejercicio físico de forma regular. La ecografía carotídea y la medida del índice íntima-media es un factor añadido para una identificación precoz de enfermedad cardiovascular y de su evolución tanto en población adulta como pediátrica.

Familial short stature and intrauterine growth retardation associated with a novel mutation in the IGF-I receptor (IGF1R) gene.

CONTEXT: IGF-I is essential for normal human growth and mediates its effects through the IGF1R. IGF1R mutations have been associated with varying degrees of intrauterine and postnatal growth retardation. OBJECTIVE: To identify IGF1R gene mutations in a short-statured family with intrauterine growth retardation and microcephaly. METHODS: Direct DNA sequencing was used to identify IGF1R mutations. Multiplex ligation-dependent probe amplification analyses were performed for deletions and duplications of all IGF1R exons. Functional studies were conducted to assess mutation pathogenicity. RESULTS: A novel heterozygous IGF1R missense mutation in exon 7 (c.A1549T, p.Y487F) was identified in a short-statured girl with severe prenatal growth retardation and microcephaly. The same mutation was also identified in her mother, who presented prenatal and postnatal growth failure, and her short-statured maternal grandmother, both of whom exhibited microcephaly. The index case showed a partial response to rhGH. Functional studies performed in dermal fibroblasts from the index case and her mother showed normal IGF-I binding; however, IGF-I activation of intracellular signalling measured as AKT and extracellular signal-regulated kinase phosphorylation was markedly reduced, with patients' values being lower than those of her mother. IGF-I stimulation of DNA synthesis was significantly reduced compared with controls. CONCLUSION: Our results show a novel missense mutation in the IGF1R gene (c.A1549T, p.Y487F) associated with prenatal and postnatal growth failure and microcephaly in the context of familial short stature. The functional studies are in line with the inactivation of one copy of the IGF1R gene with variable expression within the same family.

Neurocognitive development of children born small for gestational age (SGA). An update.

The aim of the present study is to confirm that being born SGA is a serious risk for a negative neurocognitive development. 233 cases have been controlled yearly and longitudinally by the same investigator, some of them 11 times, showing 25,8 % an IQ less than 2 SD, being less affected the catch-up + group (15 %), compared to the catch-up - group (31,4 %). The GH therapy (n 64) started before the age of 6 (n 38) or after 6 (n 26), doesn't improve the negative outcome.

Growth hormone does not alter CYP2A6 activity in growth hormone-deficient children.

A large number of metabolic alterations are increasingly being treated with growth hormone. Despite the fact that growth hormone is known to be the main regulator of several hepatic drug metabolizing enzymes in rodents, few studies deal with the effect of growth hormone on hepatic enzyme activities in human beings. The aim of this study was to determine the effects of growth hormone replacement therapy for 4 weeks on CYP2A6 activity in children, because changes in this enzyme activity may have important therapeutic and toxic consequences. A total of 31 growth hormone-deficient children (age range 4.1-13.1 years; mean age 9.88 +/- 2.89 years) participated. The genotypes of CYP2A6 gene, CYP2A6*1A, CYP2A6*1B, CYP2A6*4, CYP2A6*1x2 and CYP2A6*9, were determined by polymerase chain reaction. To assess the enzyme activity, we used caffeine as a probe drug at two points in time: before starting growth hormone therapy (Day 0) and after 4 weeks of growth hormone therapy (Day A). Caffeine and metabolite concentrations in urine were assayed by high-pressure liquid chromatography. The metabolite ratio 1,7-dimethilxanthine to 1,7-dimethylurate (17U/17X) served to indicate CYP2A6 activity. Median value and 95% confidence interval at baseline was 1.08 (0.98-1.24). The value after treatment was 1.08 (0.86-1.21). Data comparison between periods showed lack of statistically significant differences (P > 0.05). The relative change, measured by the ratio of medians and 90% confidence interval, was 1.02 (0.84-1.19). There were no significant differences when the ratio between genotype groups were compared. These results indicate that growth hormone replacement therapy of growth hormone-deficient children for 4 weeks does not modify the CYP2A6 activity and hence the efficacy or toxicity of the CYP2A6 substrate compounds.

Major determinants of height development in Turner syndrome (TS) patients treated with GH: analysis of 987 patients from KIGS.

Little is known about factors determining height outcome during GH treatment in Turner syndrome (TS). We investigated 987 TS children within the Kabi International Growth Study (KIGS) who had reached near adult height (NAH) after >4 y GH treatment (including >1 y before puberty). Through multiple regression analysis we developed a model for NAH and total gain. Our results were as follows (median): 1) At start, age 9.7 yrs, height (HT) 118.0 cm (0.0 TS SDS), projected adult height 146.1 cm, GH dose 0.27 mg/kg wk; 2) NAH HT 151.0 cm (1.5 TS SDS); 3) Prepubertal gain 21.2 cm (1.6 TS SDS); 4) Pubertal gain 9.4 cm (0.0 TS SDS). NAH correlated (r = 0.67) with (ranked) HT at GH start (+), 1 year responsiveness to GH (+), MPH (+), age at puberty onset (+), age at GH start (-), and dose (+). The same factors explained (R = 0.90) the total HT gain. However, HT at GH start correlated negatively. Karyotype had no influence on outcome. Evidently, height at GH start (the taller, the better), age at GH start (the younger, the better), the responsiveness to GH (the higher, the better) and age at puberty (the later, the better) determine NAH.

Lack of effect of growth hormone replacement therapy on CYP1A2 and xanthine oxidase activities in growth hormone-deficient children.

BACKGROUND AND OBJECTIVES: The recombinant human growth hormone (rhGH) is being increasingly used for a number of metabolic alterations. GH is the main regulator of several hepatic drug metabolizing enzymes in rodents. In addition, GH could play a major role in defining the interface between pharmacogenetics and development. However, little is known about the effect of GH on the activity of hepatic enzymes in children. The aim of this study was to determine the effect of rhGH replacement therapy for 4 weeks on CYP1A2 and xanthine oxidase (XO) activities in children. METHODS: We used caffeine as a probe drug to assess the enzyme activities at two points in time: before starting GH treatment (day 0) and after 4 weeks on rhGH therapy (day A). A total of 31 GH-deficient children (age range: 4.1-13.1 years, mean age: 9.88+/-2.89 years) participated. Urinary concentrations of caffeine and metabolites were determined by high-performance liquid chromatography (HPLC) to calculate the metabolite ratios: (AFMU+1X+1U)/17U for CYP1A2 and 1U/(1X+1U) for XO. RESULTS: Four weeks of GH substitution did not importantly alter the markers of the enzyme activities measured in this study. Median values and 95% confidence intervals (CI) at baseline were 5.17 (3.87-5.59) for the CYP1A2 ratio and 0.62 (0.56-0.65) for the XO ratio. These values, after treatment, were 4.57 (3.90-5.97) for the CYP1A2 marker and 0.62 (0.59-0.67) for the XO ratio. Data comparison between periods showed lack of statistically significant differences (P>0.05). The relative changes measured by the ratios of medians and 90% CI were 1.14 (0.90-1.31) and 0.99 (0.94-1.06) for CYP1A2 and XO, respectively. CONCLUSIONS: The absence of significant changes in the markers of enzyme activities CYP1A2 and XO suggests that rhGH replacement therapy of GH-deficient children for 4 weeks could not noticeably modify the efficacy or toxicity of substrates of these metabolic enzymes.

Effects of growth hormone deficiency and rhGH replacement therapy on the 6beta-hydroxycortisol/free cortisol ratio, a marker of CYP3A activity, in growth hormone-deficient children.

OBJECTIVE: To determine the effect of both growth hormone deficiency (GHD) and rhGH replacement therapy on CYP3A activity as well as the potential influence of gender. METHODS: The sample consisted of 35 GHD children (16 males and 19 females), aged 2.9-13.1 years, and a control group of 35 healthy children matched for age and sex. The urinary ratio 6beta-hydroxycortisol/free cortisol was used as a marker of CYP3A activity. In patients, urine samples were collected at two times, prior to starting rhGH replacement treatment and 30 days after beginning therapy. RESULTS: A significantly higher metabolic activity in GHD children was observed in relation to controls ( P=0.0001) without sex differences. Paired comparisons demonstrated a sexually dimorphic effect of rhGH therapy on the CYP3A activity. While boys displayed a significant decrease ( P=0.003), girls showed no significantly different values of CYP3A marker ( P>0.05). Unpaired comparison between controls and GHD children after therapy demonstrated absence of significant differences in boys ( P>0.05) and a strikingly higher activity in girls ( P=0.0001). CONCLUSIONS: The data suggests that: (a) GHD in children increases CYP3A activity in a non-sex-dependent manner, (b) rhGH treatment for 30 days to GHD children results in a sexually dimorphic effect on CYP3A activity, with a significant decrease in males toward normalization in relation to controls and non-significant changes in females. The results of this study may have important clinical implications for GHD children, since changes in CYP3A activity importantly affect the metabolism of both steroid hormones and CYP3A substrate drugs.