Final height in short children born small for gestational age treated with growth hormone

The aim of this observational study was to assess the long-term growth responses to GH treatment of children born small for gestational age (SGA). GH treatment was begun before puberty and continued to final height (FH). Seventy-seven short (height SD score below -2) prepubertal children born SGA (below -2 SD for birth weight and/or birth length), with a broad range of GH secretory capacity, were treated with GH in a daily dose of 33 microg/kg (0.1 U/kg), beginning before the onset of puberty. We observed a difference between adult and pretreatment projected height of 1.3 SD (9 cm) for the entire group. Among the children treated for >2 y before puberty, this mean gain (i.e. difference) in final height was 1.7 SD, whereas the mean gain was 0.9 SD among those in whom treatment was begun <2 y before puberty. Better catch-up growth was observed in the younger (r=-0.56, p<0.0001), shorter (r=-0.49, p<0.0001), and lighter (r=-0.46, p<0.0001) subjects. We conclude that GH treatment improves the final height of short children born SGA. The height gain attained before the onset of puberty is maintained to final height. The younger, shorter, and lighter the child at the start of GH treatment, the better the response. Moreover, most of these SGA individuals treated with GH reach their target height.     

Growth and growth hormone in children born small for gestational age

Although most children born small for gestational age catch up in growth by age 2 y, up to 14% remain more than 2 standard deviations below the mean for height. Recombinant growth hormone is approved by the US Food and Drug Administration and by the European Agency for Evaluation of Medicinal Products for the treatment of children born small for gestational age who fail to manifest catch-up growth by 2 y or 4 y, respectively.

Conclusion: We conclude from clinical studies that growth hormone therapy can induce catch-up growth in these children.     

Growth hormone therapy in short children born small for gestational age

Being born small for gestational age (SGA) is one of the most common causes of childhood short stature, and recombinant GH therapy has been recently licensed to promote growth in short SGA children from the age of 4 years old. Studies are now reporting very encouraging effects on adult height gains, especially in those children who started GH therapy early, at least 2 years prior to the onset of puberty. Compared to the age at starting treatment, the GH dose has a less significant impact on final height, and more attention needs to be paid now to identify earlier those SGA children who fail to catch-up spontaneously. The benefits are not just in terms of height, but also in body composition and possibly blood pressure and lipid levels. However the risk of side effects and long-term complications, particularly related to the expected metabolic effects of GH in inducing insulin resistance and hyperinsulinaemia, need to be carefully monitored especially in SGA children with a family history of type 2 diabetes. Recently, GH therapy was found to amplify the adrenarche of short SGA children and to induce a pro-inflammatory shift, as judged by a rise of neutrophil count and circulating interleukin-6 (IL-6), and a fall in adiponectin levels. Further progress is anticipated to assess the addition of insulin-sensitizing therapy to attenuate the GH-induced hyperinsulinemia, in order to alter the pro-inflammatory course, to avoid excessive release of adrenal androgens, and to slow down the potential rapid tempo of pubertal progression in SGA children. In the meantime, post-SGA short stature is rapidly becoming one of the prime indications for GH therapy in childhood.     

Growth hormone secretion and sensitivity in children born small for gestational age

This short communication discusses aspects of growth hormone (GH) secretion and GH insensitivity in short children born short for gestational age (SGA).     

Natural growth in children born small for gestational age with and without catch-up growth

This first report from a population-based postnatal growth study of 3650 healthy Swedish subjects born at full term provides new reference values for height and weight and shows that over the last 20 years there has been a small secular trend in height (0.2–0.4 SDS over the whole age range) in Sweden in both boys and girls. Within this cohort, 111 (3.1%) were of low birth weight (below –2 SDS) and 141 (3.5%) were of low birth length (below –2 SDS); 54 (1.5%) were both light and short at birth. Of the children born small for gestational age, 87% showed full catch-up growth within 2 years of life. They attained puberty at a normal or early age and reached a mean final height of –0.7 SDS. The remaining subgroup of 13% born small for gestational age remained below –2 SDS throughout childhood and reached puberty somewhat early. Their mean final height was –1.7 SDS. The current data set is too small to identify possible background factors, but it is being expanded with this objective in mind.     

Efficacy and safety of growth hormone treatment in children born small for gestational age in Japan

Growth-promoting effects and safety of growth hormone (GH) treatment in prepubertal short-statured children born small for gestational age (SGA) were evaluated in a multicenter, open-label, randomized parallel-group comparison study. Patients were randomized to two dose groups; 34 and 33 patients received GH at 0.033 and 0.067 mg/kg/day for one year, respectively. The increase of the mean height velocity standard deviation score (SDS) was significantly (p <0.0001) higher in the 0.067-mg group (from -1.4 to 4.7) than that in the 0.033-mg group (-1.9 to 2.6). A significant (p <0.0001) increase in the mean height SDS was established in the 0.067-mg group; increases of -3.1 to -2.5 vs -3.1 to -2.2 in the 0.033- and 0.067-mg groups, respectively. The trial was non-eventful. Oral glucose tolerance tests indicated a mostly normal pattern of plasma glucose before and after 12-month GH treatment. The growth-promoting effect was significantly higher with GH treatment at 0.067 mg/kg/day.     

Longitudinal follow-up of growth in children born small for gestational age

Postnatal growth was followed in a population-based group of 123 small-for-gestational-age (SGA, birth weight < -2 SD) children (66 boys and 57 girls) to four years of age in order to determine the incidence and time of catch-up growth. Gestational age was determined by ultrasound in gestational weeks 16–17 in all pregnancies, thus eliminating the problem of distinguishing between SGA and preterm infants. Infants with well-defined causes for slow growth rate, i.e. those infants with chromosomal disorders, severe malformations, intrauterine viral infections or cerebral palsy, were excluded. The boys showed an extremely fast weight catch-up, 85% of them reaching weights greater than -2 SD at the age of three months and remaining above this level to the end of the study period. Such a fast catch-up growth was observed in only two-thirds of the girls, but at four years of age 85?4 of the girls were also above -2SD. Length catch-up was more gradual than weight catch-up. Of the boys, 54% had lengths below -2 SD at birth, 26% at 1 year of age, 22% at 2 years of age, 17% at 2.5 years of age and 11% (n= 8) at 4 years of age. Corresponding figures for girls were: 69% at birth, 28%) at 1 year, 15% at 2 years, 12% at 2.5 years and 5%) (n = 3) at 4 years. At 4 years of age, only six boys and three girls remained below -2 SD for both weight and height. We conclude that in Sweden the prognosis for catch-up growth for an SGA child, when children with well-defined causes of growth disturbances are excluded, is very good and it is extremely rare for the child still to have a height below -2 SD by the age of 4 years.     

生长激素治疗宫内生长迟缓生后持续矮小儿的临床研究

目的 用生长激素治疗宫内生长迟缓（IUGR）生后持续矮小和生长激素缺乏症（GHD）儿，并进行疗效评估。方法 分泌型重组人生长激素，剂量0.1U(kg.d) ,每日1次，于晚上睡觉前30min皮下注射，结果 IUGR组及GHD组经6个月治疗后身高增长率分别为1.03cm/月及1.12cm/月，两组间差异不显著，血清胰岛素样生长因子I（IGF-I）两组均有升高，GHD组升高程度大于IUGR组。结论 生长激素对策 后持续矮小及GHD儿均有良好治疗效果。     

Reduced insulin sensitivity during growth hormone therapy for short children born small for gestational age

OBJECTIVES: To examine the influence of recombinant human growth hormone (rhGH) therapy on insulin sensitivity in short children born small for gestational age (SGA). STUDY DESIGN: Twelve short (height standard deviation score, -3.2 +/- 0.1) non-GH-deficient children SGA (7 boys/5 girls) were studied at 9.3 +/- 1.0 years of age. The insulin sensitivity index was measured with Bergman's minimal model before (11 children) and during (12 children) rhGH therapy (21 +/- 6 months) administered daily at 20 IU/m(2) per week. No child had a change in pubertal status during the study. In addition, 5 children who remained prepubertal had insulin sensitivity remeasured 3 months after rhGH therapy was suspended. RESULTS: With rhGH therapy, insulin sensitivity fell 44% +/- 10% (P =.018), with a compensatory rise in the acute insulin response of 123% +/- 59% (P <.009). Reassessment of insulin sensitivity in 5 children (3 boys/2 girls) 3 months after suspension of rhGH occurred at 9.9 +/- 0.7 years. Insulin sensitivity remained unchanged after rhGH therapy was stopped: 31.6 (20.5-42.3) before treatment, 11.5 (5.7-24.4) with treatment, and 10.7 (6.2-16.9) 10(-4). min(-1) microU/mL after treatment. CONCLUSIONS: Children SGA are known to have reduced insulin sensitivity. There was a further reduction in insulin sensitivity with rhGH therapy that did not recover 3 months after rhGH therapy was stopped.     

Growth of short children born small for gestational age and their response to growth hormone therapy

Growth hormone [GH] is licensed for use in children born small for gestational age (SGA) who fail to catch-up. We retrospectively compared the response of twenty children born SGA (who satisfied the auxological criteria) to growth hormone (Group I) versus randomly selected age and sex matched controls from a group of SGA children with growth related complaints, not treated with GH (Group II). After 2 years of GH therapy the HAZ increased from ?2.8 to ?1.6 in Group I, compared 2.2 to -1.7 in group II (P-value < 0.05). The percentage of pubertal children rose from 55% to 65% in cases versus 60% to 75% in the controls (P>0.05). GH resulted in increase in growth velocity Z-score during the first year and (4.3±0.5 in Group-I versus — 0.5±0.6 in Group-II, P<0.05) second year of treatment (1.7±0.4 in cases versus -0.6±0.7 in controls, P<0.05).Thus, GH improves height of short SGA children without accelerating pubertal progression.     

Postnatal management of growth failure in children born small for gestational age

Objectives

To discuss the etiology and growth consequences of small size at birth and the indications, effects, and safety of biosynthetic growth hormone therapy in children born small for gestational age.

不同剂量重组人生长激素治疗小于胎龄儿矮小症的疗效分析

目的 研究不同剂量重组人生长激素(rhGH)治疗小于胎龄儿(SGA)矮小症的效果和安全性。方法 收集SGA 矮小症患儿37 例,并根据使用剂量分为2 组:小剂量(每日0.1~0.15 IU/kg)rhGH 治疗组和大剂量rhGH 治疗组(每日0.16~0.2 IU/kg),比较两组患儿治疗后3、6、9、12 及24 个月时身高标准差的增长值(ΔHtSDS)、生长速率(HV)、血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平及空腹血糖等指标的变化。结果 大、小剂量rhGH 治疗后ΔHtSDS 及HV 均有提高,但大剂量组治疗后9、12 及24 个月时ΔHtSDS 及HV 均高于小剂量组(P<0.05)。大剂量和小剂量的rhGH 治疗均使血清IGF-1 和IGFBP-3 水平提高,且血清IGF-1 和IGFBP-3 水平与HtSDS 呈正相关。大小剂量组各有1 例患儿出现一过性空腹血糖轻微升高(均为6.1 mmol/L);两组甲状腺功能均无异常。结论 rhGH 治疗SGA 矮小症效果确切,不良反应少,其中大剂量较小剂量治疗更具优势。     

Cardiovascular risk factors in parents of short children born small for gestational age

Small for gestational age (SGA) children have a higher prevalence of cardiovascular risk factors at a young age. It is not known whether this increased risk is caused by their size at birth, a familial predisposition for cardiovascular disease or smallness at birth or a combination of these factors. The cardiovascular risk profile of parents of SGA children is unknown. We compared anthropometry, blood pressure, fasting serum lipid, glucose, and insulin levels of 482 parents (mean age 41 y) and 286 short SGA children with age- and sex-matched references. We also investigated whether these parameters correlated between parents and their offspring. Mothers had higher systolic blood pressure, fathers had a higher body mass index and parents had more frequently high fasting glucose levels than age- and sex-matched references. Children had significantly higher systolic and diastolic blood pressure than sex- and height-matched references. Twenty-four percent (mothers) and 10% (fathers) were born SGA but they did not have more cardiovascular risk factors than those born appropriate for gestational age. Cardiovascular risk factors did not correlate between parents and children. In conclusion, parents of short SGA children have a modest increase in some cardiovascular risk factors but risk factors did not correlate between parents and children.     

Pubertal development in children born small for gestational age

Reduced fetal growth appears to be associated with precocious adrenarche, early puberty and polycystic ovary syndrome with subsequent fertility problems. We investigated pubertal development and DHEAS levels in children born small for gestational age (SGA) and children born appropriate for gestational age (AGA). Physical examination was carried out twice. Mean age (+/-SD) at the first visit: SGA group, 9.1+/-1.1 yr; AGA group, 9.0+/-1.1 yr. AT FOLLOW-UP: SGA group, 11.6+/-1.0 yr; AGA group, 11.6 +/-1.1 yr. Pubertal stages of the children were assessed. Pubic hair was recorded as a measure of androgenization. Chronological age (CA) was expressed as a percentage of the age corresponding to the pubertal stage (CA/pubertal age [PA] x 100%). Estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) were measured in all children. FIRST VISIT: All children were prepubertal without signs of pubarche. DHEAS concentrations were higher in SGA children than in AGA children (p = 0.004). FOLLOW UP: Twenty SGA children and 15 AGA children were pubertal. CA/PA x 100% was lower in SGA girls than in AGA girls (p = 0.004). Since 2.5 years earlier all girls had been prepubertal, this means a more rapid progression in the SGA girls. CA/PA x 100% was similar in SGA and AGA boys (p = 0.1). DHEAS levels tended to be higher in SGA children than in AGA children (p = 0.06). These data support that a low birth weight may have long-lasting effects on pubertal development, as observed in a more rapid progression in SGA girls. In prepubertal SGA children, an exaggerated adrenarche is observed compared to AGA children, which tended to persist through puberty.