Hormonal changes during puberty. IV. Longitudinal study of acrenal androgen secretions.

Longitudinal studies of plasma dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone (DHEA) were made in 13 girls aged 7 years and 14 aged 10 years, during 3 years, at 6-month intervals. Similarly, two groups of 12 boys aged 8 years and 11 years were followed. In addition, 3 girls with premature adrenarche and 4 male patients with Addison's disease were studied. In the normal girls a significant rise of plasma DHEA-S and DHEA occurred from 6 years of bone age (51.4 +/- 9.0 ng/ml and 50.5 +/-9.2 ng/100 ml, respectively) to 8 years (119. 7 +/- 19.1 ng/ml and 94.5 +/- 16.5 ng/100 ml). A further significant rise was apparent at 11 years (385.8 +/-60.9 ng/ml) and 329.0 +/- 78.4 ng/100 ml). In boys, a similar rise of DHEA-S and DHEA was observed between 6 years of bone age (75.8 %/- 12 ng/ml and 44.3 +/- 7.6 ng/100 ml) and 8 years (157.4 +/- 28.9 ng/ml and 76.1 +/- 8.9 ng/100 ml). Furhter significant rise of DHEA-S and DHEA were seen at 13 years of bone age (563.7 +/- 123.7 ng/ml and 267.9 +/- 50.0 ng/100 ml, respectively). Testosterone in both sexes rose 2-3 years later than DHEA-S and DHEA. In female patients with premature adrenarche, higher plasma levels of DHEA-S and DHEA were found when compared to normal levels at similar chronological and bone ages. Very low plasma concentrations of DHEA-S and DHEA were obsrved in the patients with Addison's disease.     

Diagnostic utility of a low-dose gonadotropin-releasing hormone test in the context of puberty disorders

OBJECTIVES: The 10-microg gonadotropin-releasing hormone (GnRH) test assesses pituitary gonadotroph responsiveness, whereas the 100-microg dose assesses maximal secretory capacity. Our aims were to establish normative data for the low-dose test in children and to evaluate the test in diagnosing common pubertal disorders. METHODS: We retrospectively classified 107 children who underwent 10-microg GnRH tests into normal prepubertal (20 boys, 10 girls), normal early pubertal (10 boys, 16 girls), constitutional delay of puberty (CDP, 13 prepubertal boys >12 years), hypogonadotropic hypogonadism (HH, 5 prepubertal boys >12 years), central precocious puberty (CPP, 19 girls) or premature thelarche/variant (13 girls). RESULTS: Peak LH response was higher in prepubertal boys >12 years compared with younger boys (p < 0.01) but showed no further change in early puberty. CDP boys had LH responses similar to prepubertal boys >12 years. HH boys showed an absent LH response which diagnosed HH with 100% sensitivity and 96% specificity. Thelarche girls had LH:FSH peak ratios lower than normal prepubertal (p = 0.001), pubertal (p < 0.05) or CPP (p = 0.001) girls. CONCLUSIONS: We have established normative values for the low-dose GnRH test in children. The test successfully differentiated HH from CDP in boys, and contributed to the differential diagnosis of CPP and premature thelarche in girls.     

Evaluation of methylation analysis for diagnostic testing in 258 referrals suspected of Prader-Willi or Angelman syndromes

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurodevelopmental disorders with interrelated genetic mechanisms because genomic imprinting within the chromosome 15q11–13 region affects both the PWS and the AS locus. Methylation analysis is one method of distinguishing between the maternally and paternally inherited chromosome 15. Here we present clinical and molecular data on a large series of 258 referred patients, evaluated with methylation analysis: 115 with suspected PWS and 143 with suspected AS. In these patients, the clinical phenotype was graded into three groups: classical (group 1); not classical but possible (group 2); not classical and unlikely (group 3). For PWS, a fourth group consisted of hypotonic babies. DNA methylation analysis confirmed the diagnosis of PWS in 30 patients (26%) and AS in 28 patients (20%). For 21 PWS patients the mechanism was established: 15 had deletions, 4 had uniparental disomy (UPD) and 2 a presumed imprinting defect. Clinically all those with an abnormal methylation pattern had the classical phenotype and none of those with a normal methylation pattern had classical PWS. For 23 AS patients in whom a mechanism was established, 17 had a deletion, 3 had UPD and 3 had a presumed imprinting defect. There was greater clinical overlap in AS, with 26 classical AS patients having a normal methylation pattern while an abnormal methylation pattern was seen in one patient from group 2. In addition, there were a further 40 patients with a normal methylation pattern in whom AS was still a possible diagnosis. Our conclusion is that methylation analysis provides an excellent screening test for both syndromes, providing ∼99% diagnosis for PWS and for AS, a 75% diagnostic rate, supplemented for the remaining 25% with an essential basic starting point to further investigations. Received: 10 February 1998 / Accepted: 7 July 1998     

A survey on growth and sexual development of adolescent students in Changhua City: growth of body height and weight

In order to understand the physical growth and sexual development of contemporary adolescents, a cross-sectional survey was conducted during the period September 1983 to May 1984. The population came from all the pupils from 4th grade up, and all the junior and senior high students of Changhua City. By using stratified cluster sampling, 1419 boys and 1599 girls participated, ranging in age from 8 to 19 years. Body weight and height were measured. Growth spurt is a unique event during adolescence. It is well shown in the distance curves and pseudo-velocity curves of body height and weight. In boys, the growth spurt of height spanned from 12.0 to 14.8 years, with peak height velocity (PHV) at 13.5 years. In girls it was from 10.0 to 12.6 years and peaked at 11.5 years. The growth spurt of weight occurred from 12.0 to 15.9 years in boys with peak weight velocity (PWV) at 14.5 years, while girls had a growth spurt at 10.0-12.7 years with PWV at 11.5 years. Girls entered into the growth spurt about 2 years earlier, and also entered into PHV, PWV, two and three years earlier respectively than boys, while boys had a more intense and longer growth during the growth spurt than girls. Between 10.0-13.0 years girls were taller than boys, and between 12.0-13.0 years they were heavier than boys. However, from 13.5 years onward girls were soon surpassed by boys both in height and weight. Growth in height after 16.5 years in boys and after 15.5 in girls was minimal. Growth in weight in boys also became minimal after 16.5 years while girls weight even dropped a little bit after 16.5 years. At the mean age of 17.5 years, boys were 168.1 cm, girls were 156.2 cm in average, boys being 12 cm taller than girls after reaching their final height.     

Causes of precocious puberty in children referred for evaluation in hospital conditions

INTRODUCTION: Symptoms of precocious puberty (PP) in children always arouse anxiety in their parents. Many children with PP are being hospitalized for the detailed diagnostic work-up. The aim of our study was to analyze the frequency of the variants of PP in children referred to our department. MATERIAL: Retrospective analysis of 119 children (103 girls and 16 boys) referred for hospitalization in the years 2003-2005 due to signs of precocious puberty was performed. RESULTS: Premature thelarche, benign variant of puberty, was diagnosed in 62 (53%) girls, in the mean age of 3.39 (+/- 2.33) years. Their mean height was within 0.7 +/- 1.1 SD. Premature pubarche was diagnosed 30 (25%) children--22 girls and 8 boys in the mean age was 7.24 (+/- 0.81) years. Their mean height was 1.3 +/- 1.0 SD and was significantly higher than normal (p < 0.0001). Premature menarche was diagnosed in 8 (7%) girls in the mean age 4.81 +/-2.26 years. Mean height in this group was normal for age (0.9+/-0.8 SD). PP was diagnosed in 19 (16%) children (11 girls and 8 boys) in the mean age 5.91 +/- 1.63 years. Mean height in this group was 1.6 +/- 0.7 SD, and was significantly higher than the mean for age (p<0.0005). GnRH-dependent type was present in 15 children, diagnosed as idiopathic in 9 girls and 1 boy. In 5 children (4 boys and 1 girl) pathology of central nervous system was found. In 4 children GnRH-independent precocious puberty was diagnosed--in 3 caused by congenital adrenal hyperplasia and in 1 boy by tumour of testis (leydigioma). CONCLUSIONS: Girls with precocious thelarche without growth acceleration present the benign variant of puberty and need clinical follow up only. Boys with clinical signs of precocious puberty should be carefully evaluated to rule out the organic cause.     

Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chr15q11.2-q13.3. Three mechanisms are known to be involved in the pathogenesis: microdeletions, uniparental disomy (UPD) and imprinting defects. Both disorders are difficult to be definitely diagnosed at early age if no available molecular cytogenetic tests. In this study, we identified 5 AS patients with the maternal deletion and 26 PWS patients with paternal deletion on chr15q11-q13 by using an innovative multiplex-fluorescent-labeled short tandem repeats (STRs) assay based on linkage analysis, and validated by the methylation-specific PCR and array comparative genomic hybridization techniques. More interesting, one of these PWS patients was confirmed as maternal uniparental isodisomy by the STR linkage analysis. The phenotypic and genotypic characteristics of these individuals were also presented. Our results indicate that the new linkage analysis is much faster and easier for large-scale screening deletion and uniparental disomy, thus providing a valuable method for early diagnosis of PWS/AS patients, which is critical for genetic diagnosis, management and improvement of prognosis.     

Molecular, cytogenetic, and clinical investigations of Prader-Willi syndrome patients.

Thirty-seven patients presenting features of the Prader-Willi syndrome (PWS) have been examined using cytogenetic and molecular techniques. Clinical evaluation showed that 29 of these patients fulfilled diagnostic criteria for PWS. A deletion of the 15q11.2-q12 region could be identified molecularly in 21 of these cases, including several cases where the cytogenetics results were inconclusive. One clinically typical patient is deleted at only two of five loci normally included in a PWS deletion. A patient carrying a de novo 13;X translocation was not deleted for the molecular markers tested but was clinically considered to be "atypical" PWS. In addition, five cases of maternal heterodisomy and two of isodisomy for 15q11-q13 were observed. All of the eight patients who did not fulfill clinical diagnosis of PWS showed normal maternal and paternal inheritance of chromosome 15 markers; however, one of these carried a ring-15 chromosome. A comparison of clinical features between deletion patients and disomy patients shows no significant differences between the two groups. The parental ages at birth of disomic patients were significantly higher than those for deletion patients. As all typical PWS cases showed either a deletion or disomy of 15q11.2-q12, molecular examination should provide a reliable diagnostic tool. As the disomy patients do not show either any additional or more severe features than typical deletion patients do, it is likely that there is only one imprinted region on chromosome 15 (within 15q11.2-q12).     

Combined cytogenetic and molecular analyses for the diagnosis of Prader-Willi/Angelman syndromes

Prader-Willi (PWS) and Angelman (AS) are syndromes of developmental impairment that result from the loss of expression of imprinted genes in the paternal (PWS) or maternal (AS) 15q11-q13 chromosome. Diagnosis on a clinical basis is difficult in newborns and young infants; thus, a suitable molecular test capable of revealing chromosomal abnormalities is required. We used a variety of cytogenetic and molecular approaches, such as, chromosome G banding, fluorescent in situ hybridization, a DNA methylation test, and a set of chromosome 15 DNA polymorphisms to characterize a cohort of 27 PWS patients and 24 suspected AS patients. Molecular analysis enabled the reliable diagnosis of 14 PWS and 7 AS patients, and their classification into four groups: (A) 6 of these 14 PWS subjects (44 %) had deletions of paternal 15q11-q13; (B) 4 of the 7 AS patients had deletions of maternal 15q11-q13; (C) one PWS patient (8 %) had a maternal uniparental disomy (UPD) of chromosome 15; (D) the remaining reliably diagnoses of 7 PWS and 3 AS cases showed abnormal methylation patterns of 15q11-q13 chromosome, but none of the alterations shown by the above groups, although they may have harbored deletions undetected by the markers used. This study highlights the importance of using a combination of cytogenetic and molecular tests for a reliable diagnosis of PWS or AS, and for the identification of genetic alterations.     

Growth curves of children with Down syndrome.

Growth curves of 105 children with Down syndrome (50 boys and 55 girls) were established. At birth height, weight and head circumference of Down syndrome children were lower than these parameters in controls. This delay remained stable until puberty. For weight there was no clear-cut pubertal growth spurt. For stature, the prepubertal growth spurt occurred earlier (at the age of 11 years in boys and 9 1/2 years in girls) than in controls but was less marked. As a result, Down syndrome patients had a short stature with a quite normal weight. These reference curves, available since prenatal diagnosis of Down syndrome is performed routinely, are helpful for monitoring normal and abnormal development in Down syndrome patients.     

Age and gender differences in the physical activity patterns of urban schoolchildren in Korea and China

Physical activity in childhood is important as it may establish adult behavior. However, few studies on physical activity in children have been conducted, especially in Asian children.We performed anthropometric measurements of 159 school children in two grades (grade 5: 10-11 years old and grade 8: 13-14 years old) from urban areas of Korea (n=79) and China (n=80). The total daily energy expenditure (TEE) was estimated for 7 consecutive days using an accelerometer.The mean height, weight, and body mass index (BMI) for boys and girls in both countries exceeded the US national reference median (CDC, 2000). Physical activity levels (PALs) were significantly higher in the grade 5 group (10-11 years old) and in girls than in boys for both grades. No significant difference in PALs or daily step-counts (STPs) was observed between 'normal' and 'overweight' subgroups based on BMI, although negative correlations were found between weight, BMI, or %body fat vs. PAL or STP among Korean girls and Chinese boys (r=0.32-0.38, all p<0.05). Daily variation in physical activity was observed in Korean children. In the Koreans (boys and girls, both grades pooled), TEE and STP were significantly lower than the 7-day average on Sundays, whereas for the Chinese population, STP did not clearly differ between the weekends and the week averages.In summary, PALs were higher in the fifth grade boys and girls than in the eighth grade children; interestingly, girls tended to have higher PALs than boys. Daily variation in physical activity was observed in Korea; children were less active on Sundays.     

A Significant Increase in the Incidence of Central Precocious Puberty among Korean Girls from 2004 to 2010

Background

Few studies have explored the trends in central precocious puberty (CPP) in Asian populations. This study assessed the prevalence and annual incidence of CPP among Korean children.

Methods

Using data from the Korean Health Insurance Review Agency from 2004 to 2010, we reviewed the records of 21,351 children, including those registered with a diagnosis of CPP for the first time and those diagnosed with CPP who were treated with gonadotropin-releasing hormone analogs.

Results

The prevalence of CPP was 55.9 per 100,000 girls and 1.7 per 100,000 boys, respectively. The overall incidence of CPP was 15.3 per 100,000 girls, and 0.6 per 100,000 boys. The annual incidence of CPP in girls significantly increased from 3.3 to 50.4 per 100,000 girls; whereas in boys, it gradually increased from 0.3 to 1.2 per 100,000 boys. The annual incidence of CPP in girls consistently increased at all ages year by year, with greater increases at older ages (≥6 years of age), and smaller increases in girls aged < 6 years. In contrast, the annual incidence remained relatively constant in boys aged < 8 years, while a small increase was observed only in boys aged 8 years. The increase of annual incidence showed significant differences depending on age and gender (P <0.0001).

Conclusions

The annual incidence of CPP has substantially increased among Korean girls over the past 7 years. Continued monitoring of CPP trends among Korean children will be informative.     

Investigations with fluorescence in situ hybridization (FISH) demonstrate loss of the telomeres on the reciprocal chromosome in three unbalanced translocations involving chromosome 15 in the Prader-Willi and Angelman syndromes

Two patients with classical features of Angelman syndrome (AS) and one with Prader-Willi syndrome (PWS) had unbalanced reciprocal translocations involving the chromosome 15 proximal long arm and the telomeric region of chromosomes 7, 8 and 10. Fluorescence isitu hybridization (FISH) was used for the detection of chromosome 15(q11-13) deletions (with probes from the PWS/AS region) and to define the involvement of the telomere in the derivative chromosomes (with library probes and telomere-specific probes). The 15(q11-13) region was not deleted in one patient but was deleted in the other two. The telomere on the derivative chromosomes 7, 8 and 10 was deleted in all three cases. Thus, these are true reciprocal translocations in which there has been loss of the small satellited reciprocal chromosome (15) fragment.     

Final height of growth hormone-treated GH-deficient children and girls with Turner's syndrome: the Dutch experience. The Dutch Advisory Group on Growth Hormone

In the Dutch growth hormone (GH) registration database there are currently 552 GH-deficient children being treated, subcutaneously, with recombinant human GH six to seven times per week. Of those, 112 who have been treated for at least 2 years have reached final height. Mean age at start of therapy was 11.70 years. Mean GH dose was 15.5 IU/m(2) body surface per week. Mean final height was 173.2 cm (boys) and 159.7 cm (girls) and -1.36 SD of the population mean. Of the patients, 73.2% and 63.4%, respectively, reached a final height above -2 SD of the population or within target limits. FH-SDS was higher compared with the results of earlier cohorts with different treatment regimens. Target height, GH peak value at diagnosis, age at start of GH therapy, height SDS (HSDS) at start of puberty, and duration of GH therapy were significantly correlated with final height. These results, combined with those of a prospective GH dose-response study, suggest that better long-term results can be obtained with early and prolonged treatment and if the GH dose is individually adapted to the short-term growth response. In an ongoing dose-response study, 68 girls with Turner's syndrome, aged 2-11 years, were randomized into three dosage groups with a daily GH dose of: (group A) 4 IU/m(2) body surface; (group B) 4 IU/m(2) in the first year of therapy and 6 IU/m(2) thereafter; (group C) 4 IU/m(2) in the first year, 6 IU/m(2) in the second year, and 8 IU/m(2) thereafter. After 4 years of GH therapy, girls aged 12 years or older started low-dose oestrogen therapy. After 7 years of GH therapy, mean HSDS in all three groups had increased to values above the third percentile for healthy girls. Mean final height and final height gain of 25 girls was 159.1 and 12.5 cm, 161.8 and 14.6 cm, and 162.7 and 16.0 cm in groups A, B and C respectively. These long-term and final height results are more favourable than the results of earlier Dutch Turner's syndrome studies. Possible explanations are the higher GH doses and/or the younger age at start of GH therapy.     

Adrenal steroidogenic defects in children with precocious pubarche.

The occurrence of nonclassical congenital adrenal hyperplasia among children with precocious pubarche is still a matter of debate. We studied the adrenal steroid response to ACTH stimulus (Synacthen, 0.25 mg i.v. bolus) in 26 Italian children (5 boys, 21 girls) who had presented pubic hair, without other signs of virilization, at ages ranging between 0.45 and 8.8 years. The control groups comprised 8 prepubertal children (5 boys, 3 girls) and 12 children at Tanner stage 2 for pubic hair development (1 boy, 11 girls). Two patients were diagnosed as having nonclassical congenital adrenal hyperplasia: 1 due to 21-hydroxylase deficiency, the other due to 3 beta-hydroxysteroid-dehydrogenase deficiency. The remainder, classified as having idiopathic precocious pubarche (PP), had adrenal androgens higher than normal prepubertal children and similar levels to those observed in early pubertal controls. In contrast to a recent report, we confirmed that mild adrenal enzymatic defects can occur in PP, and, consequently, the use of ACTH testing in children with PP seems to be recommended.     

儿童身高生长追踪研究

以北京市106名儿童为样本 ,为研究各年龄生长速度的集中趋势、变异状况以及与生长速度有关的参数 ,追踪观察这些儿童自6、7岁至 18岁时共12年的身高变化 ,并做有关参数分析。报告了各年龄组身高生长速度的均值及标准差 ,该组儿童身高生长突增开始年龄 (男10.73±1 .12岁 ,女 9.00± 1.18岁 )及速度 (男4.51± 0.65cm/年 ,女 4.95± 0.79cm/年 ) ;身高生长高峰发生年龄 (男 1 3.0 7±1.08岁 ,女11.32± 1.32岁 )及速度高峰值 (男10 .01± 1.59cm/年 ,女8.13± 1.03cm/年 ) ;以及生长突增结束年龄 (男16.18± 1.02岁 ,女 13.96± 1.09岁 )。分析了最终身高与生长突增有关指标的相关关系。     

Changes in lung, airway, and chest wall function in boys and girls between 8 and 12 yr

Maximum expiratory flows, maximum inspiratory and expiratory pressures, and lung volumes were measured in 248 8-yr-old and 215 12-yr-old healthy school children. Eight-year-old girls had smaller total lung capacity but higher volume-corrected expiratory flows than boys. Maximum expiratory flow and total lung capacity increased more in girls than in boys between 8 and 12 yr. Girls had a greater increase in residual volume (0.23 liter for girls, 0.16 liter for boys) as well as lower maximum expiratory and inspiratory pressures (P less than 0.001). Girls have smaller lung volumes than boys, so one would expect smaller airways in girls, but girls generate greater flows, indicating that their airways are possibly wider than those of boys. There is also evidence of unequal growth of the airways and air spaces between 8 and 12 yr. Chest wall development appears less in girls than boys and the difference becomes more marked at 12 yr.     

Molecular characterization of Prader-Willi syndrome by real-time PCR

Prader-Willi syndrome (PWS) is a contiguous gene syndrome caused by the loss of function of genes situated within the 15q11-q13 region. The loss of function arises as a result of paternally derived mutations complemented by maternal imprinting. The molecular events underlying the disorder include interstitial deletions (70%), uniparental disomy (UPD) (25%), imprinting center defects (<5%), and rarely chromosomal translocations (<1%). The standard diagnosis of PWS is based on clinical observations and genetic investigations involving DNA methylation studies and fluorescence in situ hybridization (FISH) analysis. The absence of a paternal methylation pattern within 15q11 is sufficient for a diagnosis of PWS, and FISH analyses are used for the additional categorization of patients as either deletion or nondeletion. The main limitation of these investigations is that they neither determine the size of the molecular deletions nor permit detection of individuals with microdeletions in the PWS imprinting center that regulates imprinting in this region. We have designed and implemented a real-time PCR assay using genomic DNA and SYBR green I intercalating dye to determine the size of the chromosomal deletions in patients with PWS. This has been successfully performed on genomic DNA isolated from both peripheral blood leukocytes and buccal epithelial cells. Through this assay, the two common deletion classes in PWS were observed, and all results were 100% concordant with previous FISH assays performed on the same patients.     

Magnesium profile in autism

The aim of the present study was to determine and compare plasma and erythrocyte concentrations of magnesium in 12 autistic children (10 boys, 2 girls), 17 children with other autistic spectrum disorders (14 boys, 3 girls), 5 girls with classic Rett syndrome, and 14 normal children (7 boys, 7 girls) of the same age. No differences in intracellular Mg were found between controls and pathological subjects; however, autistic children and children with other autistic spectrum disorders had significantly lower plasma concentrations of Mg than normal subjects (p=0.013 and p=0.02, respectively). Although our study population was small, we conclude that children with autistic spectrum disorders require special dietary management. If these cases are diagnosed at an early stage, they can be helped through diet.     

Serum IGF-I and IGFBP-3 levels of Turkish children during childhood and adolescence: establishment of reference ranges with emphasis on puberty

AIMS/METHODS: We established age- and sex-related reference ranges for serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in 807 healthy Turkish children (428 boys, 379 girls), and constructed a model for calculation of standard deviation scores of IGF-I and IGFBP-3 according to age, sex and pubertal stage. RESULTS: Serum IGF-I and IGFBP-3 concentrations tended to be higher in girls compared to boys of the same ages, but the differences were statistically significant only in pubertal ages (9-14 years) for IGF-I and only in prepubertal ages for IGFBP-3 (6-8 years) (p < 0.05). Peak IGF-I concentrations were observed earlier in girls than boys (14 vs. 15 years, Tanner stage IV vs. V) starting to decline thereafter. IGFBP-3 levels peaked at age 13 and at Tanner stage IV in both sexes with a subsequent fall. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage followed by a rapid increase in IGF-I in the early pubertal stages. A relatively steeper increase in IGF-I but not in IGFBP-3 levels was observed at age 10-11 years in girls and at 12-13 years in boys which preceded the reported age of pubertal growth spurt. At late pubertal stages, both IGF-I and IGFBP-3 either did not change or decreased by increasing age. Interrelationships between growth factors and anthropometric measurements have been described, and the physiologic consequences of these have been discussed in detail. CONCLUSIONS: Differences in the pattern of IGF-I and IGFBP-3 in the present paper and those reported in other studies emphasize the importance of locally established reference ranges. Establishment of this reference data and a standard deviation score prediction model based on age, sex and puberty will enhance the diagnostic power and utility of IGF-I and IGFBP-3 in evaluating growth disorders in our population.     

Epidemiological study of wheeze,doctor diagnosed asthma,and cough in preschool children in Leicestershire.

OBJECTIVE--To determine the cumulative prevalences of wheeze and doctor diagnosed asthma and the point prevalences of recurrent cough and wheeze in children aged 5 years and under. DESIGN--Questionnaire survey of population based random sample of children registered on regional authority''s child health index for immunisation; questionnaire completed by parents. SETTING--Leicestershire. SUBJECTS--1650 white children born in 1985-9 who were surveyed in 1990. MAIN OUTCOME MEASURES--Cumulative prevalences of wheeze and doctor diagnosed asthma and point prevalences of recurrent cough and wheeze by age and sex. RESULTS--There were 1422 replies (86.2%; 726 for boys, 696 for girls). Overall, 11.0% (95% confidence interval 9.4% to 12.6%) of children had formally been diagnosed as having asthma, the cumulative prevalence in boys (12.7%) being somewhat higher than in girls (9.2%) (age adjusted odds ratio 1.47, p = 0.03). As expected, the cumulative prevalence of asthma increased significantly with age (7.5% (13/173) in children under 1 year, 15.9% (61/383) in children of 4 years and over; p < 0.001). The cumulative prevalence of wheeze overall was 15.6% (13.7% to 17.5%), being higher in boys (17.6%) than in girls (13.5%) (odds ratio 1.38, p = 0.03). The overall prevalence of recurrent cough without colds was 21.8% (19.6% to 23.9%), with a non-significant excess in boys (23.1% v 20.4%). The overall prevalence of wheezing attacks during the previous 12 months was 13.0% (11.3% to 14.8%) with a non-significant excess in boys (14.5% v 11.5%). CONCLUSIONS--These findings are baseline results and emphasise the importance of studying the age group of interest rather than relying on the recall of parents of school age children.