Pubertal growth in chronic renal failure

We evaluated the growth records of 15 boys and 14 girls who developed end-stage renal failure before or during puberty and who were regularly followed from the onset to the end of their pubertal growth spurt. Height data were smoothed by using the kernel estimation method. Mean values for age, height, and height velocity at defined points of the pubertal growth period were compared with those of normal children entering puberty both at an average and late age. The start of the pubertal growth spurt was delayed by 2.5 y in both sexes. Its duration and intensity were significantly reduced. Mean pubertal height gain was 17.3 cm in boys and 13.9 cm in girls, i.e. 58 and 48% of that observed in the late maturing control group. Mean height at the onset of the pubertal spurt in the patients was the same as that in the late maturing healthy girls and 1.0 SD below that of corresponding boys. During the pubertal growth spurt, mean height declined to -2.9 SD in boys and -2.3 SD in girls. Although skeletal maturation was increasingly retarded, we did not observe accelerated growth velocity during late puberty. Our data indicate that most patients reaching end-stage renal failure before or during puberty irreversibly lose growth potential during this period. Renal transplantation did not consistently improve pubertal growth.     

Sexual maturation in early adolescence and alcohol drinking and cigarette smoking in late adolescence: a prospective study of 2,129 Norwegian girls and boys

Early sexual maturation has been associated with higher involvement in risk behaviour during early and mid-adolescence. In a prospective study of 2,129 girls and boys, we investigated whether the timing of sexual maturation was associated with cigarette smoking and alcohol drinking in late adolescence and whether this relation differed between boys and girls. Nine hundred and eighty boys and 1,149 girls, who participated in a cross-sectional study in middle school, were included in a follow-up study in high school 4 years later. Self-rating of pubertal status, as registered at baseline in middle school, was used to indicate the timing of sexual maturation. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs), estimated by logistic regression, were used to assess the association between sexual maturation and alcohol drinking and daily smoking at follow-up. We found that girls who had matured early (OR 1.7, CI 1.2–2.4) or late (OR, 1.5, CI, 1.1–2.2) were both more likely to report more advanced drinking in late adolescence than were girls who were on time. Boys who had matured late were less likely (OR 0.5, CI 0.3–0.8) than boys who were on time to engage in advanced drinking. In general, daily smoking was more common among girls than boys, and more common among girls who had matured early (OR 1.5, CI 1.1–2.2) than among girls who were on time. Adjustment for social factors, e.g. parental education and marital status and parental drinking and smoking habits, did not substantially influence these results. We concluded that, for girls, but not for boys, early sexual maturation was associated with more advanced drinking and higher frequency of smoking in late adolescence. In boys, late sexual maturation was associated with reduced risk of advanced drinking.     

Growth and sexual maturation in children after kidney transplantation

Linear growth and sexual maturation were assessed in 68 long-term pediatric renal allograft recipients (43 boys) receiving daily or alternate-day prednisone therapy. Growth was analyzed both during the prepubertal period and during puberty. Height at transplantation was greater than 2 SD below the mean in 34.2% of prepubertal children. After the first posttransplant year, 59.2% of the prepubertal children had a normal height increment (greater than 4.8 cm/yr). Onset of puberty was recorded at a chronologic age of 14.6 +/- 1.9 years in boys and 13.3 +/- 1.9 years in girls. Height at onset of puberty related to chronologic age was -2.4 +/- 1.3 SD. Height velocity during puberty was within normal limits in 62.5% of the children. No significant difference in pubertal growth was detected in patients who had received transplants before and after the onset of puberty. Duration of pubertal development was within normal limits. In girls, menarche was achieved at a mean chronologic age of 15.9 years and bone age 12.9 years. Adult height was attained at an average age of 20.3 years in boys and 18.7 years in girls. Overall, one third of the children attained an adult height greater than 2 SD below the mean. Our data indicate that although poor growth before kidney transplantation has a great influence on adult height, the loss of growth potential during pubertal development seems even more important.     

Growth and Sexual Maturation in Paediatric Patients Treated by Dialysis and Following Kidney Transplantation

Linear growth and sexual maturation were assessed in 48 children during dialysis treatment and in 68 children following renal transplantation. Height at the onset of haemodialysis treatment was more than 2 SD below the mean in 33% of prepubertal children. During dialysis treatment most children showed a progressive deterioration in SD score. The onset of puberty and sexual maturation was delayed but was in accordance with bone age. After transplantation 59% of prepubertal children had a normal height increment. Onset of puberty was recorded at a chronological age of 14.6 ± 1.9 years in boys and 13.3 ± 1.9 years in girls. The peak of the pubertal growth spurt was 6.6 ± 1.6 cm/year in boys and 6.5 ± 2.9 cm/year in girls. The duration of pubertal development in transplanted children was within normal limits. In transplanted girls menarche was achieved at a mean chronological age of 15.9 years and bone age of 12.9 years. Adult height was achieved at a mean age of 20.3 years in men and 18.7 years in women. Overall, one third of the children attained an adult height more than 2 SD below the mean. These data indicate that poor growth is achieved in most children on dialysis treatment; following transplantation normal growth may be restored. However, poor growth before kidney transplantation and the loss of growth potential during pubertal development have a great influence on adult height.     

Frequent growth disorders in puberty and adolescence

About 50% of our patients with concern about their actual or final height are adolescents (girls greater than 11 years, boys greater than 13 years). Growth data of 103 adolescent patients (70 boys, 33 girls) seen in 1988/89 are analysed. 85% of the patients (90% of the boys) complained of short stature (length less than 3rd centile) whereas tall stature (height greater than 97th centile) was more frequently concerning girls (9 out of 16 patients). Genetic short stature and constitutional delay of growth and adolescence (CDGA) were most often diagnosed in short stature patients. When retardation of physical maturation is a major concern in patients with CDGA, treatment with a low dose of sex steroids leads to an acceleration of growth and pubertal development. This advancement of maturation is important for reducing the psychosocial difficulties of the concerned adolescents. Constitutional tall stature was the most frequent diagnosis in our tall adolescent patients. If predicted final height is above 185 cm for girls or 200 cm for boys the administration of height dose sex steroids (ethinylo-estraidol or conjugated oestrogen for girls, testosteron for boys) for height reduction can be tried, since a reduction in height between 3.5 cm and 7.9 cm has been reported for girls and similar data exists for boys. Nevertheless a cautious approach must be advocated for the administration of oestrogens because possible long term hazards can not yet be excluded.     

Height,weight, body mass index and pubertal development reference values for children of Turkish origin in the Netherlands

The aim of this study was to provide growth and sexual maturation reference data for Turkish children living in The Netherlands. We also compared these references with the reference data of children of Dutch origin and with Turkish reference data collected in Turkey and elsewhere in Europe. Cross-sectional growth and demographic data were collected from 2,904 children of Turkish origin and 14,500 children of Dutch origin living in the Netherlands in the age range 0–20 years. Growth references for length, height, weight for height, body mass index (BMI) and head circumference were constructed with the LMS method. Reference curves for sexual maturation and menarche were estimated by a generalised additive model. Predictive variables for height and BMI were assessed by univariate and multivariate regression analyses. Young Turkish adults were 10 cm shorter than their Dutch contemporaries. Mean height was 174.0 cm for males and 160.7 cm for females. Height differences in comparison with Dutch children started at 3 years. Height SDS was predominantly associated with target height. The height of Turkish children living in the Netherlands was similar to Turkish children in Germany and to children from high socio-economic classes in Istanbul. Compared to Dutch children, maturation stages started 0.5–0.7 years later for both sexes. In girls, median age at menarche was 12.8 years, 5 months earlier than in Dutch girls. BMI of Turkish children was higher than that of Dutch children at all ages. BMI SDS was associated with birth weight and the duration of stay of the mother in the Netherlands. Conclusion:Turkish children are considerably shorter and more overweight than Dutch children. Separate growth charts for Turkish children in The Netherlands are useful for growth monitoring.Abbreviations BMI body mass index - SD standard deviation - SES socio-economic status - TH target height     

Retrospective longitudinal growth study of boys and girls active in sport

Longitudinal records from the Wroclaw Growth Study and the Wroclaw Longitudinal Twin Study were screened for individuals who were active in sport during childhood and adolescence and who were active in sport as young adults. The resulting sample was 25 boys and 13 girls. Heights and weights of the active boys indicated a growth pattern characteristic of early maturers. which was verified in advanced skeletal, sexual and somatic maturation during adolescence. The pubertal progress of active boys suggested no differences in tempo compared to nonathletic boys. In contrast, girls active in sport presented a pattern of growth and maturation characteristic of average maturing individuals, but were taller and heavier than local reference data. Skeletal and chronological ages of active girls did not differ, and the active girls did not differ from local reference data in sexual maturation. PHV, however, was reached later by about one-half of a year. The pubertal progress of girls active in sport did not differ from that of nonathletic girls.     

Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height prediction

To determine how accurately several methods of height prediction estimate adult height, we compared height predictions calculated by the Bayley-Pinneau, Roche-Wainer-Thissen (RWT), target height, and Tanner-Whitehouse Mark I (TW-MI), and Mark II (TW-MII) methods with final adult height in 37 boys and 32 girls with short stature and constitutional delay of growth and puberty. They were first seen at a chronologic age (mean +/- SD) of 14.80 +/- 1.70 years (boys) and 12.87 +/- 2.56 years (girls). Adult height at 23.14 +/- 1.95 years and 21.05 +/- 2.02 years was 170.4 +/- 5.4 cm (boys) and 157.8 +/- 4.2 cm (girls), respectively, and thus within the lower range of normal. Height predictions were calculated for the total group and for patients with parents of normal (group 1) as well as short stature (group 2). For boys, the RWT method gave very accurate results, underestimating adult height by -0.6 cm for the total group. The prediction errors for the other methods were -7.3 cm (TW-MI), -4.2 cm (TW-MII), and +3.1 cm (Bayley-Pinneau method) or +1.7 cm (target height). For girls, no method was superior in estimating adult height. The mean prediction error was -0.8 cm, -2.1 cm, and -1.8 cm with the Bayley-Pinneau, TW-MI, and TW-MII methods, respectively. In contrast, adult height was overpredicted by +2.3 cm and +1.2 cm with the RWT and target height methods. We conclude that patients with short stature and constitutional delay of growth and puberty reach an adult height in the lower range of normal. Height prediction methods differ with respect to their accuracy and their tendency to overestimate or underestimate adult height.     

Relationships between age of puberty onset and height at age 18 years in girls and boys

Background

Changes during puberty may influence final adult height. Height is related to multiple health conditions, including lung function. We investigated the association between the age of onset of five puberty events and height at age 18 years, analyzing boys and girls separately.

Methods

Of 1456 children recruited into the Isle of Wight birth cohort (1989–1990), 1313 were followed up at age 18 years. Height was measured, and age of pubertal onset was collected at age 18 years. Cluster analysis was performed on the five puberty events in boys and girls and linear regression was applied with the clusters predicting height at age 18 years. Individual linear regression analyses assessed the age of onset of each pubertal event as a potential predictor for height at age 18 years.

Results

Of the 1313 children followed up at age 18 years, 653 were males and 660 were females. All puberty variables had high internal consistency. In girls, earlier age of menarche, breast development, and growth spurt were related to shorter height. In boys, earlier age of growth spurt and slower progression through puberty were related to taller height at age 18 years.

Conclusions

Given that boys and girls may have opposing associations between pubertal timing and adult height and that height is an important predictor of lung function, the effect of pubertal timing on respiratory health should be explored.     

Does constitutional delayed puberty cause segmental disproportion and short stature?

We have reviewed the growth of 98 boys and 34 girls with constitutional delay of growth and puberty followed until final height. At presentation chronological age was 14.1 (1.3) years (SD) in the boys and 13.0 (1.3) years in the girls. At presentation all patients were either prepubertal or in early pubertal maturation (4 ml testicular volume in the boys and breast stage II in the girls). Twenty-nine boys (30%) and 2 girls (6%) were treated with either sex or anabolic steroids. Mean height SDS in the boys at presentation was –2.7 (0.7) which rose to –1.9 (0.9) at final height attainment. This was significantly lower than the predicted final height SDS of –1.4 (0.8) and mid-parental height SDS of –0.5 (0.7). Similar results were obtained for the girls with a height SDS at presentation of –3.2 (0.8) which increased to –2.3 (0.7) at final height which was significantly lower than predicted final height SDS of –1.7 (0.6) and mid-parental height SDS of –0.8 (0.8). Both sexes had a relatively short sitting height at presentation; sitting height SDS –3.4 (1.0) and subischial leg length SDS –2.2 (1.0) in the boys and sitting height SDS –3.6 (1.1) and subischial leg length SDS –2.5 (0.7) in the girls. The relative disproportion between the segments had no significant change at final height. We are unable to explain the failure to achieve final height potential and the relatively disproportionate stature. Our data suggest that the late timing of the onset of puberty may be deleterious to spinal growth and consequently final height. The relatively short spinal length at presentation of constitutional delay of growth and puberty does not correct at the attainment of final stature.     

When and how to combine growth hormone with a luteinizing hormone-releasing hormone analogue

The effect of combined treatment with growth hormone (GH) and a luteinizing hormone-releasing hormone (LHRH) analogue, or GH alone, on pubertal height gain was assessed in an uncontrolled study in 15 boys and 10 girls with GH deficiency (GHD). Seven boys and six girls were treated with GH alone (group 1), and eight boys and four girls were treated with a combination of GH and an LHRH analogue during puberty (group 2). Mean ages (+/- SD) at the start of GH treatment and at the onset of puberty were significantly lower in group 2 (8.0 +/- 3.3 years and 11.2 +/- 0.8 years, respectively, in boys, and 6.3 +/- 1.6 years and 10.8 +/- 0.7 years in girls) than in group 1 (12.8 +/- 1.9 years and 13.7 +/- 1.4 years in boys, and 11.2 +/- 1.0 years and 12.5 +/- 1.2 years in girls). Height at the onset of puberty was less in group 2 than in group 1, but the difference was significant only for the boys. Combination treatment was started at a mean age of 11.7 +/- 1.2 years in boys and 11.5 +/- 1.0 years in girls. The duration of the combination treatment was 5.1 +/- 1.5 years in boys and 2.3 +/- 0.7 years in girls. The duration of the period between the onset of puberty and the end of GH treatment was significantly longer in group 2 (6.8 +/- 1.2 years in boys and 5.5 +/- 1.0 years in girls) than in group 1 (4.3 +/- 1.6 years in boys and 3.6 +/- 1.4 years in girls). The pubertal height gain was also significantly greater in group 2 (36.7 +/- 6.5 cm in boys and 29.0 +/- 8.3 cm in girls) than in group 1 (21.9 +/- 4.1 cm in boys and 18.6 +/- 4.1 cm in girls). Final height was significantly greater in group 2 than in group 1 in boys. Although there was no significant difference in final height between groups in the girls, the change in height SDS from the start of GH treatment until final height was significantly greater in group 2 (2.7 +/- 1.6 in boys and 4.5 +/- 0.5 SD in girls) than in group 1 (1.0 +/- 0.8 in boys and 1.8 +/- 0.9 SD in girls), in both boys and girls. In conclusion, it appears that combination of an LHRH analogue and GH may increase the pubertal height gain and the final height of children with GHD. The improvement is attributed to the prolongation of the treatment period, permitting slow bone maturation, and to the maintenance of height velocity. This combination treatment appears to be more effective in boys than girls. To fully assess this therapeutic approach, prospective controlled studies are needed.     

Bmi in childhood and its association with height gain, timing of puberty, and final height

No large population-based study has addressed the question of how overnutrition is related to subsequent height gain in childhood, timing of puberty, and final height. The present data represent a large Swedish population-based longitudinal growth study. Height gain in childhood, timing of reaching peak height velocity and height gain during adolescence, and final height were regarded as the short-term, interim, and long-term outcomes of childhood nutritional status, i.e. body mass index (BMI) change between 2 and 8 y. Midparental height was adjusted as the genetic influence on linear growth of the child. Childhood BMI gain was related to an increased height gain during the same period, i.e. an increase of 1 BMI unit was associated with an increase in height of 0.23 cm in boys and 0.29 cm in girls. A higher BMI gain in childhood was related to an earlier onset of puberty; the impact on the timing of puberty was 0.6 y in boys and 0.7 y in girls. Each increased unit of BMI gain in childhood also reduced the height gain in adolescence, 0.88 cm for boys and 0.51 cm for girls. No direct correlation was shown between childhood BMI gain and final height. We conclude that overnutrition between 2 and 8 y of age will not be beneficial from a final height point of view, as the temporary increase in height gain in childhood will be compensated by an earlier pubertal maturity and a subnormal height gain in adolescence.     

Anabolic steroid and gonadotropin releasing hormone analog combined treatment increased pubertal height gain and adult height in two children who entered puberty with short stature

We studied the effect of gonadal suppression treatment in combination with anabolic steroid on pubertal height gain and adult height in two children who entered puberty with short stature. Patient 1 was a female with idiopathic short stature. She received combined treatment with an anabolic steroid (stanozolol) and a gonadotropin releasing hormone analog (leuprorelin acetate). Her pubertal height gain was 28.5 cm, which is greater than that in normal height girls (20-25 cm). Patient 2 was a male with Aarskog syndrome. Although his growth hormone (GH) secretion was normal, he received GH treatment. Since GH administration did not accelerate his growth, he received combined treatment with stanozolol and leuprorelin acetate. His pubertal height gain was 27.0 cm, which is greater than that observed in GH deficient boys treated with GH alone (21.9 cm). Combined treatment with stanozolol and leuprorelin acetate appears to be effective in increasing pubertal height gain and adult height in children who enter puberty with short stature.     

Long-Term Results with a Slow-Release Gonadotrophin-Releasing Hormone Agonist in Central Precocious Puberty

ABSTRACT. As part of an ongoing international multicentre study, 19 children (14 girls, 5 boys) with central precocious puberty (CPP) were treated with a slow-release gonadotrophin-releasing hormone (GnRH) agonist, triptorelin, for 4 years. After 3 years of treatment, height velocity stabilized at 4.0 cm/year. Predicted adult height (mean ± SD) increased from 158.9 ± 6.8 to 164.9 ± 6.6 cm in girls (n = 14, p < 0.01), and from 174.4 ± 18.5 to 184.3 ± 17.1 cm in boys (n = 4, p < 0.05). In 12 additional girls who had started the multicentre study but discontinued triptorelin treatment after 2.2 ± 0.5 years, menses started 9.8 ± 3.7 months after cessation of treatment in all but one patient. Height velocity increased over the first 6 months after discontinuation of treatment, from 3.6 ± 0.1 to 5.4 ± 2.5 cm/year, and remained higher than pretreatment values in the second 6 months, but decreased subsequently. Bone maturation increased, and no significant improvement in predicted adult height was observed. For auxological reasons, therefore, it may be advisable to continue triptorelin treatment for as long as possible. Concomitant growth hormone (GH) therapy was initiated in three girls with CPP with height velocities of 3.2–3.6 cm/year after 3 years of treatment with triptorelin and predicted adult heights of less than the third centile for Dutch girls. Prior to the administration of GH, all patients had subnormal 24-hour GH profiles and GH responses to arginine provocation. GH treatment increased height velocity markedly in all girls, and improved predicted adult height. It is concluded that triptorelin therapy improves predicted adult height. In children with CPP and genetic short stature, with a markedly decreased height velocity during triptorelin therapy, concomitant administration of a GnRH agonist and GH may have advantages. Further extensive studies are required.     

Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene

OBJECTIVES: Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) are ubiquitous toxic environmental contaminants. Prenatal and early life exposures affect pubertal events in experimental animals. We studied whether prenatal or lactational exposures to background levels of PCBs or DDE were associated with altered pubertal growth and development in humans.Study design: Follow-up of 594 children from an existing North Carolina cohort whose prenatal and lactational exposures had previously been measured. Height, weight, and stage of pubertal development were assessed through annual mail questionnaires. RESULTS: Height of boys at puberty increased with transplacental exposure to DDE, as did weight adjusted for height; adjusted means for those with the highest exposures (maternal concentration 4+ ppm fat) were 6.3 cm taller and 6.9 kg larger than those with the lowest (0 to 1 ppm). There was no effect on the ages at which pubertal stages were attained. Lactational exposures to DDE had no apparent effects; neither did transplacental or lactational exposure to PCBs. Girls with the highest transplacental PCB exposures were heavier for their heights than other girls by 5.4 kg, but differences were significant only if the analysis was restricted to white girls. CONCLUSIONS: Prenatal exposures at background levels may affect body size at puberty.     

Spontaneous growth in idiopathic short stature. European Study Group

Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.     

Constitutional delay of growth and puberty: from presentation to final height

This retrospective study evaluated clinical characteristics of patients with constitutional delay of growth and puberty (CDGP) at presentation, during puberty and at final height. The records of 151 children (105 boys, 46 girls) with CDGP were reviewed and the results were evaluated with respect to findings in healthy Turkish schoolchildren. CDGP was twice as frequent in boys as in girls. Height and weight deficit and short sitting height of the children were evident at presentation and continued up to final height. Mean age of onset of puberty was retarded by 2.5 years in girls and by 3 years in boys. The time between onset of puberty and pubertal growth spurt was shorter in both girls and boys than in the controls. Peak growth velocity was compromised in both girls and boys. Forty-one patients (30 boys, 11 girls) reached final height (FH). Mean FH was shorter than both target height and predicted adult height. The Bayley-Pinneau method was found to be a better predictor of FH than either the Tanner-Whitehouse method or target height. FH also showed correlation with the father's height. There was no effect of testosterone treatment on final height. Height deficit at onset of puberty, shorter duration between onset of puberty and pubertal growth spurt, compromised peak growth velocity and short upper segment due to delayed puberty, are findings which may explain the decreased final height of children with CDGP.     

Spontaneous growth in idiopathic short stature. European Study Group.

Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.     

Influence of growth hormone treatment on pubertal timing and pubertal growth in children with idiopathic short stature. Dutch Growth Hormone Working Group

We studied the influence of recombinant human growth hormone (rhGH) on pubertal timing and pubertal growth in children with idiopathic short stature (ISS), and evaluated whether this was different between children with and without intra-uterine growth retardation (IUGR). Twenty-six (18 M, 6 IUGR; 'treated') subjects were treated with rhGH (6-7 days/week, dosage: 14-28 IU/m2 per week [i.e. 0.2-0.3 mg/kg per week]). Fifty-eight subjects (31 M, 9 IUGR; 'controls') were not treated. All subjects attained final height. Prepubertal height gain was significantly larger in the treated children compared to control children (M: 0.66 SDS, 95% confidence interval [CI] 0.41 to 0.92; F. 0.92 SDS, CI 0.58 to 1.26). Pubertal height gain, peak height velocity and duration of puberty were similar for the treated and control subjects. rhGH advanced the age at peak height velocity by 0.7 years (CI 0.3 to 1.0) in boys, and the age at onset of puberty by 1.1 years (CI 0.3 to 1.9) in girls. The gain in final height was 2-3 cm. Age and height SDS at start were the most important predictors for pubertal height gain, total height gain and final height in a multivariate regression analysis. Total height gain of treated subjects with IUGR was less than that of treated subjects without IUGR. In conclusion, rhGH did not affect pubertal growth in children with ISS, and slightly improved their final height. rhGH treatment should be started early to improve height as much as possible before the onset of puberty.     

Statural growth in Williams-Beuren syndrome

The spontaneous growth of 165 patients (75 girls and 90 boys) with Williams-Beuren syndrome was analysed in a mixed longitudinal and cross-sectional manner. Mean (±1 SD) length at birth was 48.2±2.6 cm in girls (n=52) and 49.0±3.0 cm in boys (n=65). Intrauterine growth retardation (length below –2 SD of the normal population) was present in 35% of the girls and 22% of the boys. Poor growth was noted during the first 2 years of life. Until age 9 years in girls and 11 years in boys, mean growth followed the 3rd percentile. A pubertal growth spurt with normal growth rate was seen at age 10 years in girls and 13 years in boys, i.e. 1 to 2 years earlier than normal. Menarche also occurred earlier than normal at a mean age of 11.6±1.5 years (n=28). Mean adult height was 153.9±6.9 cm in girls (n=17) and 168.2±6.9 cm in boys (n=27), approximately corresponding to the 3rd percentile in both sexes and correlating with the genetic height potential (target height). The mean deficit of adult height compared to target height was 10.2 cm in girls and 9.1 cm in boys. Skeletal development progressed at an approximately normal rate in both sexes.