小于胎龄儿生长相关异常及生长激素治疗

小于胎龄儿(SGA)又称宫内生长迟缓(IUGR)，一般指出生体重低于同胎龄、同性别平均体重的第十百分位以下或同胎龄平均体重2个标准差的新生儿。人群中SGA的发生率约为3％～10％，在中国为7．5％。大部分SGA儿生后出现追赶生长而达到正常范围，但仍有10％～15％不能赶上，其中约半数至成年后身高会低于正常平均身高的2个标准差，对这部分儿童可应用生长激素(GH)，以促进生长，改善最终身高。现主要介绍SGA儿的内分泌、GH治疗对SGA儿的生长发育及代谢的影响。     

不同类型小于胎龄儿的生长发育比较

各国报道的小于胎龄儿发生率约为3％。小于胎龄儿是导致围生期患儿发病和死亡的重要原因之一,且预后与成年期多种疾病相关。仅通过出生体重来判断小于胎龄儿的生长受限不够全面,因为未考虑到小于胎龄儿的身体比例。根据孕期影响因子的来源、作用于胎儿的时间和作用严重程度的不同,会产生两类小于胎龄儿：匀称型小于胎龄儿和非匀称型小于胎龄儿。二者出生后的体格和神经发育情况可能存在差异。该文通过比较各分类指标,并在各分类指标下探讨匀称型小于胎龄儿和非匀称型小于胎龄儿的体格神经发育差异。     

生长激素治疗小于胎龄儿的有关问题

小于胎龄儿(SGA)是指出生体质量位于同胎龄平均体质量的第10百分位数以下或低于2s的小儿,其成年后易出现身材矮小、代谢性疾病及心血管疾病。近年来,重组人生长激素(rhGH)治疗身材矮小的儿童取得了不错的效果,其应用指征也得到了极大的丰富。本文就rhGH在SGA的应用,包括剂量、治疗年龄、对机体代谢的影响及不良反应进行简要综述。     

小于胎龄儿大脑的发育及与适于胎龄儿的比较

人脑生长的关键期在妊娠中期至生后二年,小于胎龄儿(SGA)的畸形发生率与死亡率都比适于胎龄儿(AGA)高,出生后体格及智能发育亦常受到影响,一些SGA出生后智能发育落后,是否与其在宫内脑发育受到影响有关?为了了解SGA大脑的发育情况,我们应用颅脑超声对SGA大脑发育情况进行了观察,并与AGA婴儿进行比较,现报告如下。对象和方法一、对象1996年11月～1997年11月在我院的SGA共48例,男21例,女27例,其中足月SGA36例,胎龄为39.7±1.4周,出生体重为2453.3±310.7g;早产SGA12例,胎龄为35.1±1.6周,出生体重为1757±298.7g。AGA共151例,男91…     

晚期早产儿与足月小于胎龄儿生长发育状况比较

目的比较均为低出生体质量的晚期早产与足月小于胎龄(SGA)儿童的生长和发育状况。方法随机选取100例出生体质量<2 500 g的3岁儿童,其中50例为晚期早产儿童,50例为足月SGA儿童,对其进行体格测量及盖赛尔(Gesell)发育量表评估。结果晚期早产和足月SGA儿童的出生体质量、出生身长相近,但3岁时晚期早产儿童的身高、体质量、头围明显优于足月SGA儿童,差异有统计学意义(P<0.05);Gesell发育评估显示,晚期早产儿童的动作能、应物能、语言能、应人能均高于足月SGA儿童,差异有统计学意义(P<0.05)。结论同为低出生体质量,晚期早产儿童的长期生长和发育状况优于足月SGA儿童。     

早产小于胎龄儿和适于胎龄儿生长发育状况随访分析

目的观察早产小于胎龄儿(SGA)和适于胎龄儿(AGA)出院后体格生长及智能发育状况。方法选择2009年2月至2012年12月出院的早产儿220例,根据出生时状况分为SGA组和AGA组,在矫正月龄7个月内定期测量身长、体质量、身长,头围,并由专职人员进行发育商测试,比较两组间差异。结果纠正1~6月龄SGA组体质量Z值均小于AGA组,差异有统计学意义(P0.05);纠正7月龄差异无统计学意义(P0.05);纠正1~5月龄SGA组身长Z值均小于AGA组,差异有统计学意义(P0.05),纠正6月龄之后差异消失;纠正1~7月龄SGA组头围Z值均小于AGA组,差异有统计学意义(P0.05)。SGA组及AGA组在纠正5~7月龄发育商分别为96.7±9.2及102.9±9.9,差异有统计学意义(P0.05);SGA组大运动、认知及语言能区得分均低于AGA组,差异有统计学意义(P0.05)。结论 SGA早产儿在纠正7月龄内体质量追赶性生长较好,但身长追赶性生长则相对较差,头围追赶最差;SGA早产儿纠正5~7月龄智能发育水平总体落后于AGA早产儿,尤以大运动、认知和语言能区落后较明显。     

小于胎龄儿相关因素的研究

为了解不同类型胎儿体格发育(出生体重、身长、头围)情况及小于胎龄儿相关因素,自1999年5月～2000年12月,对在我院分娩的单胎活产新生儿及其母亲424对,进行前瞻性调查.结果显示小于胎龄儿(SGA)36例,发生率为8.5%,适于胎龄儿(AGA)294例,大于胎龄儿(LGA)94例,SGA组除出生体重外,身长、头围三项指标均低,与AGA组有非常显著意义(P值均＜0.001).影响SGA体格发育Logis-tic回归分析最主要危险因素为母孕早期剧吐、被动吸烟、贫血、羊水量过少和母患妊高征.母亲身高、文化程度、胎盘重量与胎儿体格发育呈正相关.SGA组新生儿生后五天内发病率最高为33.3%,与AGA组的2.7%比较有非常显著意义(P＜0.01).因此,防治常见妊娠合并症,加强孕期营养,提高自我保护意识,将有助于降低SGA发生.     

小于胎龄儿相关因素的研究

为了解不同类型胎儿体格发育（出生体重，身长，头围）情况及小于胎龄儿相关因素，自1999年5月－2000年12月，对在我院分娩的单胎活产新生儿及其母亲424对，进行前瞻性调查。结果显示：小于胎龄儿（SGA）36例，发生率为8．5％，适于胎龄儿（AGA）294例，大于胎龄儿（LGA）94例，SGA组除出生体重外，身长，头围三项指标均低，与AGA组有非常显著意义（P值均＜0．001），影响SGA体格发育Logistic回归分析：最主要危险因素为母孕早期剧吐，被动吸烟，贫血，羊水量过少和母患妊高征，母亲身高，文化程度，胎盘重量与胎儿体格发育呈正相关，SGA组新生儿生后五天内发病率最高为33．3％，与AGA组的2．7％比较有非常显著意义（P＜0．01），因此，防治常见妊娠合并症，加强孕期营养，提高自我保护意识，将有助于降低SGA发生。     

小于胎龄儿的研究进展

我国小于胎龄儿（SGA）发生率并不低。发病机制复杂,包括胎盘、孕母和胎儿因素,其中胎儿因素越来越受到重视,尤其遗传学方面的进展。生后管理涉及追赶性生长和生长以外多系统近远期并发症的防治,前者需注意适度追赶和生长激素应用的禁忌证,后者涉及神经发育和认知、心血管和代谢并发症、青春期发育和生殖健康等。宫内和宫外生长迟缓（IUGR/EUGR）因有相似的风险,需受到临床医生同样的重视。     

Cranial ultrasound in preterm infants: long term follow up.

One hundred and twenty nine high risk preterm infants (gestational ages 26-36 weeks, mean 31.2 weeks; birth weights 800-3880 g, mean 1490 g) were studied by cranial ultrasound during the neonatal period, over a period of one week to three months, and at the age of 1 year. Neonatal ultrasound scanning was performed with an ATL Mk III real time echoscope, and follow up ultrasound scans at the age of 1 were performed with an Octoson static compound scanner. The neonatal scans of 66 infants were abnormal. Cerebroventricular haemorrhages were detected in 53 infants and other lesions in 19, six of whom also had haemorrhages. Posthaemorrhagic changes developed in 30 infants. The follow up scans at 1 year were abnormal in 27 children. One large parenchymal cyst was detected. All 27 scans showed ventricular dilatations; 19 were asymmetrical. About 95% of the children with normal neonatal scans and 60% with abnormal neonatal scans had normal scans at 1 year. The size and shape of the ventricular system had changed in 20% of all infants. As no major changes were seen in the ultrasound images of those studied beyond the age of 2 months cranial ultrasound follow up in high risk preterm infants should therefore be continued until the age of 2-3 months; follow up beyond that age would only rarely be necessary.     

Comparison of growth hormone releasing hormone therapy and growth hormone therapy in growth hormone deficiency

Seven children with growth hormone deficiency of hypothalamic origin responded to an i.v. bolus of growth hormone releasing hormone (GHRH) (1–29)-NH2 with a mean serum increase of 10.7 ng/ml growth hormone (GH) (range 2.5–29.3 ng/ml). Continuous s.c. administration of GHRH of 4–6 g/kg twice daily for at least 6 months did not improve the growth rate in five of the patients. One patient increased his growth rate from 1.9 to 3.8 cm/year and another from 3.5 to 8.2 cm/year; however, the growth rate of the latter patient then decreased to 5.4 cm/year. When treatment was changed to recombinant human growth hormone (rhGH) in a dose of 2 U/m² daily, given s.c. at bedtime, the growth rate improved in all patients to a mean of 8.5 cm/year (range: 6.2 to 14.6). Presently GHRH cannot be recommended for the routine therapy of children with growth hormone deficiency since a single daily dose of rhGH produced catch-up growth which GHRH therapy did not.Abbreviations GH growth hormone - GHD growth hormone deficiency - GHRH growth hormone releasing hormone - hGH human growth hormone - rhGH recombinant human growth hormone - SM C/IGF I somatomedin C/insulin-like growth factor I On the occasion of the 85th birthday of Prof. Dr.Dr.h.c. mult. Adolf Butenandt     

Growth and growth hormone secretion in children after bone marrow transplantation

Long-term sequelae of bone marrow transplantation (BMT) are a major concern among long-term survivors since the procedure has been considerably developed over the past decade. In this study, linear growth and growth hormone (GH) secretion were evaluated in 25 children (14 males and 11 females) with various neoplastic or non-neoplastic hematological disorders who had survived for more than 3 years after BMT. Impaired linear growth after BMT, as defined by a change in height standard deviation score (SDS) by more than ? 1.0 SD, was observed in 14 patients (56%). Four children showed severe growth suppression with a decrease in SD score by more than 2.0, and 10 exhibited a moderate reduction by between 1.0 and 2.0 SD. A recovery of normal height velocity was observed in those who had received BMT at a younger age. The type of disease, a difference in preconditioning regimen, the presence of chronic graft-versus-host disease or a GH secretory capacity 1 year after BMT were not contributing factors for impaired growth. A serial examination of GH secretion with insulin-induced hypoglycemia demonstrated that poor GH secretion was not necessarily a prerequisite for impaired growth. These results indicate that the secretory status of GH does not predict the future growth pattern of children who received BMT.     

Changes with growth hormone treatment in growth hormone deficient children

A total of 54 previously untreated patients (15 girls, 39 boys) with poor growth due to idiopathic growth hormone deficiency (IGHD) were treated with human growth hormone (hGH), continuously up to 4 years. All of the patients had a peak hGH level which was below 10 ng/mL after at least two pharmacological tests and/or blunted physiologic hGH secretion, and their height was below ?2.5 s.d. for age and gender. After the 1st year of therapy, height velocity (HV) increased significantly when compared with baseline (from 3.18 ±0.76 cm/year to 9.17±1.03 cm/year; P <0.001), declined during the 2nd year and then remained significantly higher than pretreatment HV. When considering improvement in height expressed by height standard deviation score (SDS), during the therapy all of the patients showed a significant gain ± 1.72±1.09 (from ?4.11±0.61 to ?2.21±0.48). The height values were significantly higher than pretreatment, but remained below ?2 s.d. after 4 years of hGH therapy in our patients. Increased height velocity has been sustained, but height improvement after therapy was inversely correlated to height SDS for chronological age of patients at the start of therapy. In conclusion post-treatment height has been shown to be related to height deficit at the beginning of therapy. Therapy was well tolerated with no local or systemic adverse effects or acceleration of bone age.     

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an iv bolus injection of growth hormone releasing hormone 1–29, 1 μg/kg, significantly enhanced the growth hormone response to the neuropeptidc, confirming the results of previous studies which used the iv route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.     

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an iv bolus injection of growth hormone releasing hormone 1–29, 1 μg/kg, significantly enhanced the growth hormone response to the neuropeptidc, confirming the results of previous studies which used the iv route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.     

Auxological, clinical and neuroradiological findings in infants with early onset growth hormone deficiency

Sixteen infants less than 2 years of age with apparently idiopathic hypopituitarism were studied. At birth, 11 of 16 patients (69%) had subnormal length associated with relative adiposity and 10 of 16 (62%) showed significant deterioration in length deficiency from birth onwards. These findings suggest that: (a) growth hormone deficiency, in a number of patients, had started well before delivery; (b) growth hormone may play a role in intrauterine growth; and (c) growth hormone may also be involved in early postnatal growth. Magnetic resonance imaging in these patients was very similar to that described in hypopituitarism of later onset. This suggests that even in the latter case, hypopituitarism may have a prenatal onset. Finally, the severity of growth failure and the coexistence of other hypopituitary symptoms at the time of diagnosis in 31 % of our patients indicate that early clinical screening of hypopituitarism is possible.     

Liver cirrhosis in cystic fibrosis--therapeutic implications and long term follow up

Experience gained from liver studies in 450 patients with cystic fibrosis, seen in a 38 year period from 1964 to 1992, is surveyed. Of these, 31 (7%) showed findings that indicated multilobular cirrhosis. There was a slight but not significant male predominance: 19 males against 12 females. Liver disease had its onset during childhood in most cases. The natural course of liver disease and of cirrhosis is protracted. All patients were routinely evaluated by way of: (i) clinical examination, (ii) biochemical studies and specifically estimation of transaminases and gamma glutamyltransferase, and (iii) liver imaging, ultrasonography, and computed tomography. The study aimed to detect early liver disease, that is multilobular cirrhosis and its complications, with a view to optimal introduction of treatment with ursodeoxycholic acid as this drug shows promise for preventing or stabilising the cirrhotic process. Effects of surgical treatment on portal hypertension are surveyed. These include portacaval shunting, partial splenectomy (considered the procedure of choice), liver transplant in the event of liver failure, or a triple transplant (liver, lungs, and heart) if necessary. One triple transplant was successfully performed in a boy of 10 years with a 2 year follow up.