Infancy Growth Pattern Related to Growth Hormone Deficiency

ABSTRACT. Linear growth during the first three years of life can be represented mathematically in terms of the "ICP-growth model", using a combination of a quickly decelerating Infancy component with the addition of a slowly decelerating Childhood component, the latter acting from the second half of the first postnatal year. The growth pattern for supine length of four children with growth hormone (GH) deficiency is related here to the first two components of this growth model. Basically, all four infants displayed a pattern in line with the exponential shape of the Infancy component to the age when GH therapy was initiated. This observation indicates the existence of the Infancy component as it has been adopted for the ICP-model, and also that it represents the part of postnatal linear growth which seems to be independent of GH. The onset of the Childhood component in healthy subjects has been observed as an abrupt increase in growth rate during the second half of the first year of life. A similar abrupt increase was observed in this study at the time of the initiation of GH therapy (16–27 months). This observation gives some further empirical support to the hypothesis that the child's age at onset of the Childhood component defines the as yet undetermined age at which GH begins to exert a significant influence on linear growth. ICP-based growth charts provide an improved instrument for early detection of GH deficiency.     

Growth Response to Human Growth Hormone Treatment in Children with Partial and Total Growth Hormone Deficiency

ABSTRACT. The growth response during the first and second years of human growth hormone (hGH) treatment was studied in 14 prepubertal children with so-called "partial" GH deficiency (peak GH between 8 and 15 mU/1) and compared to 28 prepubertal children with "total" GH deficiency (peak GH less than 8 mU/1). There was no difference in growth acceleration between children with partial and total GH deficiency, when initial covariables were taken into account. In a stepwise multiple regression analysis initial stature, pre-treatment growth velocity and skinfold thickness were shown to be most related to growth response, but after exclusion of 3 children with a genetic form of total GH deficiency and partial TSH deficiency this relationship was lost. GH levels during provocation tests and auxological criteria have a poor predictive value for growth response to hGH therapy.     

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??Objective??To describe height velocity in pre-pubertal Growth Hormone Deficiency??GHD?? children without recombinant human growth hormone??rhGH?? treatment and explore the height velocity targets for the first year in response to rhGH treatment. Methods??Analyze retrospectively the height velocity data without??HV0?? and one year after ??HV1?? rhGH treatment in physiologic dose??0.7 U/??kg·w???? in pre-pubertal GHD children above 3 years old who were diagnosed from Jan??2000 to Dec??2009 in our hospital. The GHD patients who were included for calculation of HV0 had peak GH value in GH provocative test less than 7 ng/ml. HV0 was calculated according to age??HV0-CA??342 patients?? and bone age??HV0-BA??257 patients?? respectively. According to the peak GH value in GH provocative test??the patients who were included for calculation of HV1 were divided into GHD-1 group????0.33 nmol/L??140 patients?? and GHD-2 group??7.0??9.9 μg/L??33 patients??. Results??Within every bone age group??GHD-1 group had significantly higher HV1 than GHD-2 group??P??0.05????11.0??10.5-11.5?? cm/a??n??34?? vs. 9.9??9.1-10.8?? cm/a??n??6?? when bone age was less than 3 years??10.4??9.8-10.9?? cm/a??n??48?? vs. 8.8??8.3??9.2?? cm/a??n??8?? when bone age was between 3 to 5 years??and 9.5??9.1-9.9?? cm/a??n??58?? vs. 8.5??8.0-9.1?? cm/a??n??19?? when bone age was between 6 to 10 years. The mean HV1 of GHD-2 was very close to the 25th percentile??P25?? of GHD-1 group. They both were significantly higher than HV0-BA. Conclusion??The recommended height velocity target for the first year after rhGH treatment in pre-
pubertal GHD children is the P25 of HV1 of GHD-1 group. It should be at least 9.9 cm/a??8.7 cm/a and 8.3 cm/a when the bone age is less than 3 years??3 to 5 years and 6 to 10 years?? respectively.     

ACCELERATION OF DELAYED GROWTH WITH FLUOXYMESTERONE

ABSTRACT. 61 boys with constitutional delay of growth and maturation, aged 9-19 years and with a bone age (BA) lag of 1.3-5.5 years, were administered fluoxymesterone (0.05-0.24 mg/kg daily orally, relative dose increasing with age) to accelerate growth. The therapy was continuous and lasted 0.4-3.6 years. The findings are compared with 37 observation periods in a similar group of untreated boys. Growth velocity increased in every treated boy during the therapy, the mean first-year increment being 4.3±1.6 cm/year. For most boys this brought about a decrease in the height difference from peers, and so afforded the psychosocial relief that was the objective of the therapy. After therapy the velocity decreased slightly hi most boys, from a mean of 9.1±1.4 to 7.1±3.3 cm/year. The effect of the intervention on final height was assessed by three relatively independent methods of prediction. These were found to be equally valid in the 15 control boys for whom final heights are known. The effect appeared to vary individually, but on the average there appeared to be no loss of height potential. No individual boy with initial BA>10.5 years showed a substantial reduction in predicted final height.     

Investigation of Growth Hormone Secretion in Patients with Intrauterine Growth Retardation

Rochiccioli, P., Tauher, M., Moisan, V. and Pienkowski C. (Department of Paediatrics, CHU Rangneil, Toulonse Cedex, France). Investigations of growth hormone secretion in patients with intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 42, 1989.
Growth hormone (GH) deficiencies have rarely been reported in intrauterine growth retardation (IUGR). This study has investigated GH secretion using GH provocation tests, 24-hour GH secretory profiles, and insulin-like growth factor I (IGF-I) measurements in 24 children with intrauterine growth retardation. The criteria for diagnosis were a birth length and weight below the 10th percentile for gestational age. The average age at investigation was 5.5 years, and the average growth retardation was -3.3 SD. Twenty children had shown catch-up growth between the ages of 6 months and 3 years, followed by varying decreases in growth velocity. Studies of GH secretion demonstrated GH deficiency in 16 patients, with neurosecretory dysfunction in six. Treatment with pituitary GH in nine children increased mean growth velocity from 3.5 cm/year to 7 cm/year. GH therapy should thus be effective in improving the height prognosis of children with intrauterine growth retardation.     

Some Introductory Concepts of Human Growth: an Overview

ABSTRACT. Growth study methodology is described with emphasis upon cross-sectional versus longitudinal methods. The uses and advantages of velocity growth data are presented. Catch-up growth is defined and measurement ratios-indices discussed. The methodology necessary for the measurement of key indicators of human growth is described. These are body weight, recumbent length, head circumference.     

Neurosecretory Dysfunction of Growth Hormone Secretion in Thalassemia Major

ABSTRACT. The growth retardation of children with thalassemia major is multifactorial. Along the endocrine axis of growth hormone (GH), serum somatomedin has been shown to be deficient and GH response to GH-relasing hormone impaired, while GH response to provocative stimuli is normal. We studied the spontaneous secretion of GH in seven patients with thalassemia major and growth retardation. Three of the patients were hypothyroid, and the other four were euthyroid. Spontaneous secretion of GH in all seven patients was subnormal: the number of pulses, the mean pulse amplitude, and the integrated concentration of GH were all lower than in 14 age- and sex-matched (10 pubertal and 4 prepubertal) control subjects. GH response to provocative stimuli was normal in the euthyroid patients. This pattern of response corresponds with the definition of neurosecretory dysfunction of GH secretion. It is concluded that the growth retardation of patients with thalassemia major is partly due to neurosecretory dysfunction of GH secretion.     

Growth and Growth Hormone Secretion in Children Following Treatment of Brain Tumours with Radiotherapy

ABSTRACT. We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n= 20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n= 36) from -0.28 to - 1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys.
Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whom were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m²/week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to + 1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group.     

Restricted catch-up growth after cessation of steroid treatment in a growth-hormone-deficient child

The phenomenon of catch-up growth has been known for a long time but its actual stimulus has remained unidentified. Involvement of growth hormone (GH) seems likely, but it is unknown whether normal GH secretion is an absolute prerequisite for catch-up growth. We present insight to this topic by describing a child with GH deficiency who showed a biphasic pattern of catch-up growth. During the first catch-up phase, she showed restricted catch-up growth in the absence of GH therapy, while she achieved nearly complete catch-up with GH therapy. Both periods of catch-up growth are compared separately with the response to GH therapy of age-matched, GH deficient patients with similar height deficit. This observation suggests that the first phase of catch-up growth in a child with severe growth retardation may be partially GH independent, while further catch-up requires normal GH levels.     

Assessment of differences in linear growth among populations in the WHO Multicentre Growth Reference Study

Aim: To assess differences in length/height among populations in the WHO Multicentre Growth Reference Study (MGRS) and to evaluate the appropriateness of pooling data for the purpose of constructing a single international growth standard. Methods: The MGRS collected growth data and related information from 8440 affluent children from widely differing ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the USA). Eligibility criteria included breastfeeding, no maternal smoking and environments supportive of unconstrained growth. The study combined longitudinal (birth to 24 mo) and cross-sectional (18–71 mo) components. For the longitudinal component, mother–infant pairs were enrolled at delivery and visited 21 times over the next 2 y. Rigorous methods of data collection and standardized procedures were applied across study sites. We evaluate the total variability of length attributable to sites and individuals, differences in length/height among sites, and the impact of excluding single sites on the percentiles of the remaining pooled sample. Results: Proportions of total variability attributable to sites and individuals within sites were 3% and 70%, respectively. Differences in length and height ranged from −0.33 to +0.49 and −0.41 to +0.46 standard deviation units (SDs), respectively, most values being below 0.2 SDs. Differences in length on exclusion of single sites ranged from −0.10 to +0.07, −0.07 to +0.13, and −0.25 to +0.09 SDs, for the 50th, 3rd and 97th percentiles, respectively. Corresponding values for height ranged from −0.09 to +0.08, −0.12 to +0.13, and −0.15 to +0.07 SDs.
Conclusion: The striking similarity in linear growth among children in the six sites justifies pooling the data and constructing a single international standard from birth to 5 y of age.     

婴幼儿出生至2岁身长和体重生长轨道变化的随访研究

目的 研究2岁内正常儿童身长、体重发生追赶生长或减速生长的状况及影响儿童身长变化的因素。方法 回顾性收集1996年8月至2008年12月,前瞻性收集2009年1月至2010年3月重庆医科大学附属儿童医院儿童保健科门诊体检儿童的资料。均以首次体检年龄<2月龄±15 d;﹤1岁,随访≥6次（至少每2个月随访1次）;～2岁,随访≥2次（至少每6个月随访1次）的原则进行随访。由专人测量儿童身长和体重,并于首次体检时询问并记录父母亲的身高。根据随访年龄,分为<2、～4、～6、～8、～10、～12、～18和～24月龄组。以首次体检（<2月龄±15 d）身长测量值为基础值计算百分位值,并计算其Z值。以～24月龄身长百分位值代表2岁时身长百分位值。生长参数参照2000年美国CDC儿童生长资料,本研究将追赶生长或减速生长定义为身长或体重百分位较前次年龄段百分位上升或下降≥1条主百分位线,且身长发生百分位线变化后能沿着新生长轨道生长,观察儿童生长轨道变化情况,采用Logistic回归分析儿童身长与儿童基础身长Z值及父母亲身高的相关性。结果 共有331名儿童(3 421人次测量数据)进入分析,其中男172例,女159例。①<2岁儿童179/331名（54.1%）的身长发生246人次追赶生长,229人次追赶生长1条百分位线,17人次追赶生长2条百分位线;56/331名（16.9%）儿童的身长出现63人次减速生长,均减速生长1条百分位线;各月龄组平均身长在P50～P75。②3～6、～12和～24月龄组儿童身长变化与母亲身高、儿童基础身长相关（均P<0.05）,～12月龄组身长变化同时还与父亲身高相关（P<0.05）。③<2岁儿童309人次体重发生追赶生长,232人次追赶生长1条百分位线,77人次追赶生长2条百分位线;641人次体重发生减速生长,596人次减速生长1条百分位线,45人次减速生长2条百分位线。各月龄组平均体重的百分位值不稳定。结论 儿童出生时的体格生长水平反映胎儿期生长,但不完全决定生后生长情况。判断2岁内儿童身长变化需综合考虑基础身长、父母亲身高遗传等因素。     

Growth monitoring of low birthweight infants: What references to use?

Growth charts are the mainstay of monitoring growth in babies who were born small or preterm. A variety of different charts are available, each with specific limitations. Most birthweight centile charts underestimate growth restriction in preterm babies and there are few good charts for monitoring longitudinal growth in preterm babies; it is important to be aware of the limitations of using cross-sectional data for monitoring longitudinal growth. Customised centile charts of fetal growth are used increasingly for antenatal monitoring for small-for-gestational age fetuses despite a lack of robust evidence. It is also unclear whether customised centile charts should be used for assessing birthweight, particularly in babies born at term. Faltering post-natal growth in preterm babies is very common but need not be universal with close attention to nutrition. Monitoring of growth trajectories through infancy following either fetal growth restriction or post-natal faltering growth is important to ensure proportional growth, particularly during periods of accelerated growth. This review will discuss these issues in the context of current practice in Australia and New Zealand.     

Growth Response in Prepubertal Children with Idiopathic Growth Hormone Deficiency during the First Year of Treatment with Human Growth Hormone. Analysis of the Kabi International Growth Study.

ABSTRACT. In order that children with growth hormone deficiency (GHD) reach the goal of normal adult stature, treatment modalities need to be optimized. From the large database of patients enrolled in the Kabi International Growth Study (KIGS), 257 prepubertal patients with idiopathic GHD undergoing their first year of growth hormone (GH) substitution therapy were selected. A multiple regression analysis was performed to determine both auxiological factors characterizing the patients and the factors related to the chosen treatment modalities which are of significance for the observed magnitude of the growth response. Due to the structure of the data, pretreatment height velocity and bone age-derived auxiological data were not considered. It was observed that the magnitude of the growth response was inversely correlated with chronological age and relative height (HT SDS) at the start of GH treatment but was positively correlated with mid-parental height. The growth response was also positively correlated with the GH dose (IU/kg/week) and the frequency of GH injections per week. A regression equation using these five parameters was derived, allowing the growth response of these patients to be predicted. The extension of this analytical approach in the future will allow the treatment of patients with GHD to be tailored to individual requirements.     

Growth Hormone Secretion and Growth Hormone Treatment in Children with Intrauterine Growth Retardation

Albertsson-Wikland, K. (Departments of Paediatrics II and Physiology, University of Gothenburg, Gothenburg, Sweden). Growth hormone secretion and growth hormone treatment in children with intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 35, 1989.
Few children with intrauterine growth retardation (IUGR) fail to show catch-up growth during the first year of life. There may he many reasons for this, ranging from disturbances of hormone production to hormonal unresponsiveness of target cells. This report presents preliminary data on growth hormone (GH) secretion and responses to GH treatment in 16 children with IUGR and poor catch-up growth, six of whom had Silver-Russell stigmata. GH secretion was assessed by measurement of the GH response to an arginine-insulin test and determination of spontaneous GH secretion over 24 hours. GH production was heterogeneous hut, more often than expected, children showed both a low response to GH provocation and low spontaneous secretion of GH. Five out of six of the children with Silver-Russell syndrome and seven out of 10 of the children with non-Silver-Russell IUGR gained more than 2 cm in height during 1 year of treatment with GH at a dose of 0.1 IU/kg/day. These results clearly demonstrate that some children with IUGR and poor catch-up growth secrete insufficient amounts of GH, and that many of these very short children show an improvement in growth rate during treatment with physiological doses of GH.     

Two-Year Results of Treatment with Methionyl Human Growth Hormone in Children with Turner Syndrome

ABSTRACT. Methionyl growth hormone (somatrem) in a daily dosage of 4 IU/m² body surface area was administered to 16 girls with Turner syndrome. Low dose ethinyl estradiol (0.1 μg/kg body weight) was added in girls aged 13 years or more. Mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) and 5.3 (1.3) cm/year in the first and second year, respectively. Bone age advanced 1.8 years over 2 years and predicted adult height was increased. Apart from the occurrence of anti-GH antibodies there were no side effects. In conclusion, somatrem is an efficacious and safe therapy for short stature in Turner syndrome over a period of 2 years. Longer follow-up is needed before conclusions about its effect on final height can be drawn.     

Fetal growth and postnatal growth failure in very-low-birthweight infants

Aim: To determine in a cohort of very-low-birthweight (VLBW) infants the incidence of postnatal growth failure and the influence of intrauterine growth and neonatal morbidities on the risk for severe postnatal growth failure (PNGF). Methods: The study was based on analysis of data from the Israel Neonatal Network database on VLBW infants born between 1995 and 2001. Z-score was determined for weight at birth and discharge, and severe PNGF was defined as a decline in z-score of greater than 2. Univariate analysis and multi-linear regression determined the effect of fetal growth and neonatal morbidities on the risk for severe PNGF. Results: Severe PNGF occurred in 10.6% of the cohort. The mean±SD birthweight (BW) z-score was -0.59±0.74, decreasing to -1.67±0.77 at discharge. The incidence of severe PNGF increased significantly with decreasing BW and gestational age. Each 1-unit increase in z-score BW was associated with a 2.37-fold increased risk for severe PNGF. Severe respiratory distress syndrome, patent ductus arteriosus, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia were associated with severe PNGF.

Conclusion: Severe PNGF among VLBW infants was markedly influenced by intrauterine growth as well as major morbidities. In the assessment of postnatal growth among VLBW infants, growth status at birth should be considered.