Does growth hormone treatment improve final height attainment of children with intrauterine growth retardation?

Twenty four children (five girls, 19 boys) who had intrauterine growth retardation were treated with daily subcutaneous biosynthetic human growth hormone, initially in a dose of either 15 or 30 U/m2/week for the first year and in the latter dose for the next two years. Six patients (one girl, five boys) had no dysmorphic signs and 18 (four girls, 14 boys) had signs of Russel-Silver syndrome. All had birth weights below the third centile when adjusted for gestation age and all the children were below the third height centile at the start of treatment. Mean age was 6.3 years (range 2.1-9.7) when growth hormone treatment was started. All had normal growth hormone secretion to either a pharmacological or physiological test. In the first year of treatment, height velocity SD score increased from -0.75 to +3.6 in the group treated with 30 U/m2/week, and from -0.77 to +1.4 in the lower dose group. After three years of treatment, mean height velocity SD score was +1.1, irrespective of which initial treatment dose had been administered during the first year. There was no difference in the growth response of children with or without dysmorphic features. However, despite the sustained increase in growth rate, there was no significant change in height for bone age SD score, pointing to an unaltered final height outcome.     

Growth hormone treatment in short children with intrauterine growth retardation

The aim of this prospective controlled study was to assess the effect of rhGH in short prepubertal children with intrauterine growth retardation and normal growth hormone status. Twenty-six children were randomized into treatment (12F, 4M) and control (6F, 4M) groups. Mean ages were 5.3 (1.3) yr and 4.3 (1.7) yr, respectively. rhGH (Genotropin) was used at a dose of 0.2 IU/kg/day as daily s.c. injections for two years. In the treated group, mean height SDS increased from -3.0 (0.5) to -1.9 (0.7) and height velocity SDS showed a significant increase from -1.3 (2.0) to 3.7 (1.8) in the first year (p < 0.001) and 1.6 (1.8) (p < 0.01) in the second year of treatment. In the controls, height SDS, initially -2.7 (1.4), and height velocity SDS, initially -0.9 (1.1), remained essentially the same during two years of follow-up. Height SDS for bone age changed by 0.6 in the treated group and 0.4 in the control group. Target height SDS--initial height SDS in the treated group improved by 1.1 SD but declined in the control group. IGF-I levels increased from 9.5 (4.2) nmol/l (72 [31.8] ng/ml) to 32.5 (27.0) nmol/l (244.4 [202.8] ng/ml) (p = 0.004) in the treated group while no change was observed in the controls. No adverse effects were encountered during rhGH therapy. It was concluded that rhGH treatment induces a significant increase in growth velocity in the short term. This outcome, as opposed to the unchanged indices in the control group over the same period, may be indicative of an improved height prognosis in short children born with intrauterine growth retardation treated with rhGH.     

Adult height in children with prepubertal short stature secondary to intrauterine growth retardation

In a retrospective study of 47 children seen before puberty for growth retardation secondary to intrauterine growth retardation (IUGR), 23 boys had a final height of 161.9 ± 8.0 cm and 24 girls a final height of 147.6 ± 7.2 cm, values that were significantly lower than the target heights of these patients ( p < 0.001). This reduction in adult height indicates the possible usefulness of growth hormone therapy in children with IUGR.     

Sustained effect of human growth hormone therapy on children with intrauterine growth retardation

Previous studies have not clarified whether human growth hormone (HGH) therapy can significantly increase the height of patients with intrauterine growth retardation (IUGR). To determine whether the initial increase in growth rate is sustained through subsequent treatment, 19 prepubertal patients who had IUGR were treated with HGH. Ten of them received a second treatment course. Growth rates (in centimeters per year) were 4.8 +/- 1.4 (mean +/- SD) for the pretreatment period, 7.6 +/- 2.3 for the first treatment period, 4.2 +/- 2.5 for the interval between treatments, 5.9 +/- 1.4 for the second treatment period, and 4.3 +/- 2.6 for the posttreatment period. Growth rates for the two treatment periods were significantly greater than for the periods before, interval between, and posttreatment. Height expressed as the number of standard deviations below the mean for age increased significantly between the onset of treatment and the most recent measurement. These data indicate that HGH has a sustained positive effect on increasing growth rates in children with IUGR, although the magnitude of the effect may decrease with further treatment. Furthermore, we suggest that it is worthwhile to treat patients who have IUGR with HGH for prolonged periods of time, if supplies exceed those necessary to treat children with growth hormone deficiency.     

Effects of growth hormone therapy in prepubertal children with short stature secondary to intrauterine growth retardation

A total of 130 short children were included in a French multicentre study and randomized between a control group (group A) and two groups treated with daily subcutaneous injections of GH at doses of 0.7 IU/kg/week (group B) and 1.4 IU/kg/week (group C) for 2 years. Height velocity was significantly increased ( p <0.0005) in groups B and C, with a greater increase in group C than in group B ( p < 0.001). The benefit after 2 years compared with controls was 4.3 cm in group B and 5.9 cm in group C. The rate of bone maturation was not affected by GH therapy. These results led to the conclusion that 2 years of treatment with GH improves final height prognosis in children with short stature secondary to IUGR, and that this effect is dose dependent. The effect on final height has still to be demonstrated.     

Endocrine profile of children with intrauterine growth retardation

BACKGROUND: Intrauterine growth retardation (IUGR) is a major cause of short stature in childhood. Most but not all children experience catch-up growth by 2 years of age. METHODS: We investigated the endocrine profile (thyroid function, prolactin, cortisol, C-peptide and insulin-like growth factor-I [IGF-IJ levels) of 57 children with IUGR, aged 2-10 years, and compared it with 30 controls whose birth weight was appropriate-for-gestational-age. RESULTS: The hormonal profile for both groups was similar for thyroid hormones, prolactin, C-peptide and IGF-I. Cortisol levels were significantly lower in the IUGR group compared to controls (p <0,05). When the IUGR group was divided into 'catch-up' growth and 'non-catch-up' subgroups, the latter had significantly lower IGF-I levels (p <0.001). CONCLUSIONS: Lower cortisol levels in children born with IUGR may reflect impaired function of the hypothalamic-pituitary-adrenal axis associated with this condition. The significantly lower IGF-I levels of the 'non-catch-up' subgroup may be involved in their failure to grow.     

Insulin resistance in short children with intrauterine growth retardation

Scientific evidence is accumulating for an association between intrauterine growth retardation (IUGR) and an increased risk of developing adult degenerative diseases, such as essential hypertension, non-insulin-dependent diabetes mellitus and ischaemic heart disease. A possible underlying mechanism for these conditions is insulin resistance. In this paper, mechanisms and methods of measurement of insulin resistance are briefly reviewed, and recent studies on the evaluation of insulin resistance in short children with IUGR are summarized. In our experience, short prepubertal children with IUGR show consistent insulin resistance, which becomes particularly evident during pubertal development.     

Insulin resistance in short children with intrauterine growth retardation

Chiarelli F, di Ricco L, Mohn A, De Martino M, Verrotti A. Insulin resistance in short children with intrauterine growth retardation. Acta Pædiatr 1999; Suppl 428: 62–5. Stockholm. ISSN 0803–5326
Scientific evidence is accumulating for an association between intrauterine growth retardation (IUGR) and an increased risk of developing adult degenerative diseases, such as essential hypertension, non-insulin-dependent diabetes mellitus and ischaemic heart disease. A possible underlying mechanism for these conditions is insulin resistance. In this paper, mechanisms and methods of measurement of insulin resistance are briefly reviewed, and recent studies on the evaluation of insulin resistance in short children with IUGR are summarized. In our experience, short prepubertal children with IUGR show consistent insulin resistance, which becomes particularly evident during pubertal development. □ Intrauterine growth retardation, insulin resistance, short children     

Language development in preschool children born after asymmetrical intrauterine growth retardation

BackgroundAfter intrauterine growth retardation, many minor neurodevelopmental disorders may occur, especially in the motor skills domain, language and speech development, and cognitive functions.AimThe assessment of language development and impact of postnatal head growth in preschool children born with asymmetrical intrauterine growth retardation.MethodsExaminees were born at term with birth weight below the 10th percentile for gestational age, parity and gender. Mean age at the time of study was six years and four months. The control group was matched according to chronological and gestational age, gender and maternal education with mean age six years and five months. There were 50 children with intrauterine growth retardation and 50 controls, 28 girls and 22 boys in each group. For the assessment of language development Reynell Developmental Language Scale, the Naming test and Mottier test were performed.ResultsThere were statistically significant differences (p < 0.05) in language comprehension, total expressive language (vocabulary, structure, content), naming skills and non-words repetition. Statistically significant positive correlations were found between relative growth of the head [(Actual head circumference ? head circumference at birth)/(Body weight ? birth weight)] and language outcome. Children with neonatal complications had lower results (p < 0.05) in language comprehension and total expressive language.ConclusionIntrauterine growth retardation has a negative impact on language development which is evident in preschool years. Slow postnatal head growth is correlated with poorer language outcome. Neonatal complications were negatively correlated with language comprehension and total expressive language.     

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y; p < 0:001)and with the firstyear of observation in Group2( p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.     

Natural history of intrauterine growth retardation: pubertal growth and adult height

The evolution of height and bone age up to complete or near complete achievement of growth has been followed in 13 children born at term with a length of 42 to 46 cm, who after age 2 years had still a growth delay of -2.1 to -4.9 SD. Their mean annual growth velocity has been slightly below the average, excepted in the years preceding and following immediately the onset of puberty. The bone age, largely delayed and close to height age up to approximatively 8 years, afterwards has increased more than growth, so that the final height has always been less than the adult height predicted at age 8 years. The main factor in this difference between final and predicted height has been the fact that puberty has not been delayed. Starting at the usual age, in children whose height deficiency was still important, the pubertal growth spurt has not allowed full catch-up. Thus, in spite of delayed bone age during childhood, the mean adult height in the 13 patients of this series has been -3.43 SD versus -3.16 SD at age 2-5 years, these mean values involving different individual growth curves with absolute deterioration in 6 only of the 13 cases. These data will have to be considered when discussing the final results of therapeutic trials in children with severe and persisting intra-uterine growth retardation.     

Thyroid hormone unresponsiveness in two siblings with intrauterine growth retardation and exophthalmos

Two cases of a brother and a sister with thyroid hormone unresponsiveness are described. They had large goiters and high levels of thyroid hormones in the face of clinical euthyroidism. The birth weight of the brother was low for his gestational age. He was also lean and exophthalmic, as is often seen in Graves' disease.Abbreviations used TSH thyrotropin - T4 thyroxine - PBI protein-bound iodine - BMR basal metabolic rate - T3 triiodothyronine - TRH thyrotropin releasing hormone - RT3U resin triiodothyronine uptake - TBG-C thyroxine binding capacity of thyroxine binding globulin - LATS long acting thyroid stimulator - hGH human growth hormone - LH luteinizing hormone - FSH follicle stimulating hormone - Gn-RH gonadotropin releasing hormone     

The cortisol-cortisone shuttle in children born with intrauterine growth retardation.

We evaluated the involvement of a possible dysfunction of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the fetal growth retardation and poor growth rates of children born with intrauterine growth retardation (IUGR). Children with IUGR have a nephron deficit and are also at risk of developing cardiovascular diseases, high blood pressure, glucose intolerance, and dyslipidemia later in life. The major site of 11beta-HSD2 production is the kidney and its deficit causes hypertension. We investigated plasma concentrations of cortisol (F) and cortisone (E) and the F/E ratio in 26 control children and in 40 IUGR children without catch-up growth. We also determined cholesterol, HbA1C, insulin, and glucose levels in plasma. Mean F values were 106 +/- 54.2 ng/mL in control children and 114.6 +/- 53.2 ng/mL in IUGR children. Mean E values were 19.5 +/- 7.1 ng/mL in control children and 17.9 +/- 6.85 ng/mL in IUGR children. The mean F/E ratio for control children was 5.5 +/- 1.7. Eight (20%) of the IUGR children (IUGR children of group 1) had high F/E ratios more than 2 SD above the normal mean: 13.15 +/- 4.26, (p < 0.0001) as compared to control children, whereas the other 32 children (IUGR children of group 2) had normal F/E ratios: 5.40 +/- 1.43 (p = 0.68). Childhood height was significantly lower for group 1 than group 2 children (-3.63 SD and -2.92 SD, respectively: p < 0.01) and was negatively correlated with the F/E ratio (p < 0.01). Systolic blood pressure was higher for group 1 (p = 0.005) and for group 2 (p = 0.015) than for control children. The diastolic pressure in IUGR children of group 1 was higher than that in control children (p = 0.013) and slightly higher than that in group 2 (p = 0.1, ns). Cholesterol concentrations were higher in group 1 than in group 2 (p = 0.029), and controls (p = 0.017) and correlated positively with F/E (0.02 < p < 0.05). Fasting insulin concentrations were higher in group 1 than in group 2 (ns) and controls (ns). There was no difference in mean fasting glucose concentrations, or HbA1C between the three groups. Twenty percent of our children with IUGR and poor growth rates had high F/E ratios, suggesting a possible partial 11beta-HSD2 deficit. Whether these children are at high risk of developing cardiovascular diseases as adults remains to be further evaluated.     

生长激素治疗造血干细胞移植后生长障碍儿童的疗效观察

目的　 观察重组人生长激素对造血干细胞移植后生长障碍儿童的疗效和安全性。方法 　用分泌型重组人生长激素 ,剂量为 1u/kg·w ,分 6～ 7次 ,于晚上睡前3 0分钟皮下注射 ,在治疗前后对比生长指标的变化 ,并随访不良反应。结果 　经治疗6个月后身高增长率较治疗前明显提高 ,血清胰岛素样生长因子 -1亦明显升高 ,未发现有严重的不良反应。结论 　生长激素能明显促进造血干细胞移植后生长障碍儿童的身高增长 ,使用安全。     

Prolonged impairment of cellular immunity in children with intrauterine growth retardation.

Cellular immunity was studied in 17 newborn infants, in eight children aged 1 to 5 years with intrauterine growth retardation, and in age-matched control subjects. At birth T and B peripheral blood lymphocytes were decreased, and delayed cutaneous hypersensitivity to phytohemagglutinin was diminished. In vitro PHA-induced lymphocyte proliferation was similar to that in control subjects but was greater than in healthy adults. In later childhood the numbers of T lymphocytes were normal, but their proliferative capacity was significantly reduced and cutaneous hypersensitivity was minimal or absent. Prolonged impairment of cellular immunity in these children may explain their increased susceptibility to infection and inadequate response to immunization, and predispose to the development of allergic, autoimmune, and neoplastic disease.