小儿死亡危险评分的临床应用

目的观察小儿死亡危险评分(PRISM评分)与PICU急性危重症患儿预后的关系。方法对2003年2-10月PICU收治急性危重症45例,回顾性评定PRISM评分,并依据评分分组,记录患儿临床资料和住院时间、预后。结果PRISM 评分<15分24例,>15分21例。两组年龄、体质量和院内感染率均无显著差异(P均>0.05)。两组死亡率分别为8.1%(2/ 24例)和38.1%(8/21例),PRISM评分<15分组死亡率明显低于>15分组(x2=4.14 P<0.05)。PRISM>15分组存活病例住院天数(13.2±6.1)d显著长于PRISM<15分组(9.7±8.5)d(t=1.74.P<0.05)。结论PRISM评分越高,死亡率随之增加。PRISM评分增高,患儿住院时间越长。PRISM评分能够准确评估急性危重症病人的严重程度和预后。     

尿IGFBP-7对危重症患儿急性肾损伤的早期预测价值

目的探讨尿胰岛素样生长因子结合蛋白7(IGFBP-7)对危重症患儿急性肾损伤(AKI)的早期预测价值。方法选择2012年5月至8月儿童重症监护病房(PICU)收治的患儿为研究对象。分为轻度AKI(AKI 1期)、严重AKI(AKI2和3期)和非AKI组。检测入PICU第一个24小时尿IGFBP-7水平,并于入PICU 24小时内行儿童死亡风险Ⅲ(PRISMⅢ)评分。以多因素logistic回归分析评估在校正混杂因素后尿IGFBP-7与AKI的关系,用受试者工作特征曲线(ROC)及曲线下面积(AUC)评价尿IGFBP-7对危重症患儿AKI的早期预测价值。结果共纳入危重症患儿144例,21例(14.6%)在样本采集120小时内发生AKI,其中严重AKI 11例。严重AKI组入PICU第一个24小时的尿IGFBP-7水平、PRISMⅢ评分均高于轻度AKI及无AKI组,差异均有统计学意义(P0.05)。Logistic回归分析显示,在校正年龄、体质量、PRISMⅢ评分后,尿IGFBP-7是严重AKI的独立危险因素(OR=2.93,95%CI:1.07～8.03,P=0.037),预测危重症患儿严重AKI的AUC值为0. 79(95%CI:0. 66～0. 92,P=0. 001)。结论尿IGFBP-7是危重症患儿严重AKI的独立预测指标,具有早期预测价值。     

����ϵͳ������֢ ����ڲ������Լ�Һ����

目的分析重症及危重症手足口病患儿脑脊液常规和生化检查结果,指导早期识别危重症手足口病患儿。方法回顾性分析2010年4至10月中国医科大学盛京医院感染科及PICU收治的197例重症和37例危重症手足口病患儿的一般临床资料和脑脊液常规生化检查,对两组结果进行分析比较。结果两组脑脊液异常总数差异有统计学意义(P<0.05),白细胞蛋白均增高患儿数量、仅白细胞增高患儿数量、仅蛋白增高患儿数量差异均有统计学意义(P<0.05)。重症组患儿脑脊液蛋白增高48例,占24.37%;危重症组患儿脑脊液蛋白增高16例,占43.24%。两组间比较差异有统计学意义(P<0.05)。两组间脑脊液白细胞数差异无统计学意义(P>0.05),而蛋白定量差异有统计学意义(P<0.05)。结论脑脊液蛋白明显增高或者单纯蛋白增高而白细胞正常的重症手足口病患儿更容易发展为危重症;危重症患儿脑脊液蛋白显著增高提示免疫机制在危重症患儿神经系统损伤中可能有重要作用。     

南非PICU患儿脓毒症流行病学调查

目的报告南非PICU危重症患儿入PICU 24 h内脓毒症发病率以及脓毒症相关病死率。     

危重症患儿炎性反应程度与胰岛功能的关系

目的探讨危重症患儿炎性反应程度与胰岛功能的变化。方法选择本院PICU2003年10月～2006年10月收治的危重症患儿96例。测定危重症患儿在疾病极期0、24h及恢复期血糖、胰岛素、C肽、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）水平。结果危重症患儿在病情极期TNF-α、CRP均明显升高,胰岛素敏感性指数显著降低（Pa〈0.01）,且在极期、恢复期变化过程中TNF-α、CRP均与胰岛素敏感性指数呈正相关。结论危重症患儿有严重的胰岛素抵抗,且炎性反应与胰岛功能可能相互影响。     

入住重症监护病房时非感染患儿动态监测C-反应蛋白、前降钙素和肾上腺髓质素前体预测医院感染的价值

摘要 目的 通过动态监测炎症指标评价其对医院感染预测的价值，并寻找入住PICU后最易发生医院感染的时点。方法 以入住PICU时非感染患儿为研究对象；以在PICU中发生医院感染结局为医院感染组，余为非医院感染组；收集4个时点的3项炎症指标［CRP、PCT和肾上腺髓质素前体（pro-ADM）］，分析炎症指标对医院感染的预测价值。绘制受试者特征工作（ROC）曲线，计算曲线下面积、敏感度和特异度等。结果 2014年10月1日至2015年2月28日入住复旦大学附属儿科医院PICU符合本研究纳入和排除标准的危重症患儿75例。医院感染组23例，非医院感染组52例，两组在一般情况、基础疾病和有创操作方面差异均无统计学意义（P均＞0.05）。两组危重症患儿在PICU中均分别得到238个CRP、PCT和pro-ADM值，医院感染组与非医院感染组的3个炎症指标水平差异均有统计学意义（P均<0.05），最佳界值分别为21.3 mg·L-1、0.85 ng·mL-1和0.86 nmol·L-1，受试者特征工作（ROC）曲线下面积分别为0.739、0.767和0.839。入住PICU至医院感染发生的时间为（118.9±70.8）h，入住PICU至距医院感染发生最近1次采血时点间隔为（96.5±66.4）h，医院感染发生与其最近1次采血时点间隔为（23.6±21.9）h。3个炎症指标不同组合，CRP+PCT+pro-ADM、PCT+pro-ADM、CRP+PCT和CRP+pro-ADM预测医院感染ROC曲线下面积分别为0.891、0.885、0.882和0.879；敏感度均为91.3%，特异度44.2%~63.5%。结论 CRP、PCT和pro-ADM单项及其组合均对医院感染有较好预测价值，入住PICU 4 d左右是适宜的以炎症指标判断医院感染的时点。     

PICU要加强介入肺科学技术建设与规范化发展

PICU中的患儿在生命体征稳定程度及疾病的严重性方面明显不同于其他患儿，PICU实施介入肺科学诊疗技术尤其适用于这些不容易或不能安全移动的危重症患儿。因此，在PICU加强介入肺科学技术的建设与规范化发展是救治患儿和儿童重症医学科建设的需要。     

急性呼吸衰竭时机械通气的临床应用

呼吸衰竭是儿科危重症中最常见的致死原因，我院PICU自1991年以来应用机械通气抢救急性呼吸衰竭68例，有效提高了临床抢救成功率。临床资料一、一般资料68例均为1991年以来经我院PICU抢救治疗的急性呼吸衰竭患儿（诊断标准参照第6版实用儿科学呼衰章节）。男39例，女29例；年龄     

中国25家儿科重症监护病房主要配置及住院状况调查分析

目的 调查中国儿科重症监护病房（PICU）的基本配置及住院患儿状况。方法 应用问卷调查中国25家PICU的基本配置，应用儿童危重病例评分和美国PICU出入院指南，对2004年1月1日至2005年6月30日各PICU 29 d至14周岁住院患儿均进行为期12个月的危重病例筛选。结果 中国25家PICU平均床位数（11.4±8.0）张，呼吸机数（6.1±3.7）台，44.0%（11/25）的PICU能进行中心静脉压监测。收治病例12 018例，危重病例60.5％（7 269/12 018）。危重病例中内科疾病占769%（5 590/7 269），外科疾病占16.8%（1 233/7 269），其他科室疾病占6.3%（456/ 7 269）；平均住院日6.3 d；肺炎41.4%（3 013/7 269），脓毒症95%（688/7 269），外伤5.5%（397/7 269），呼吸衰竭27.6%（2 009/7 269）； 行机械通气26.9 %（1 957/7 269），行机械通气>24 h 17.9%（1 300/7 269），ARDS 1.44%（105/7 269）。研究期间，危重病例中病死率为6.7%（485/7 269，95% CI:6.1%～7.3%），PICU中病死率为40%（485/12 018，95% CI:3.7%～4.4%）。主要疾病病死率为1.3%～61.0%，不同PICU间收治患儿及病死率均存在差异。结论 中国PICU配置仍处于初级水平，收治患儿标准及危重患儿病死率可能存在差异。     

儿童早期预警评分在识别危重患儿病情中的价值

目的 探讨儿童早期预警评分（PEWS）识别危重患儿病情的价值。方法 选取2016年1~12月由中南大学湘雅医院普通病区转入PICU或急诊收入PICU的患儿120例为PICU组,该院该期间入住普通病房的120例患儿作为对照组。对PICU组的120例患儿根据病种的不同分为呼吸/循环系统疾病亚组（55例）和神经/其他系统疾病亚组（65例）。记录患儿入院时的PEWS评分,采用受试者工作特征（ROC）曲线分析PEWS评分对病情评估的价值。结果 PICU组PEWS评分显著高于对照组（P < 0.05）。呼吸/循环系统疾病亚组的PEWS评分显著高于神经/其他系统疾病亚组（P < 0.05）。以患儿是否收住PICU为预测指标时,PEWS评分的最佳截断值为3.5分,灵敏度为85%,特异度为95%,ROC曲线下面积为0.951（95% CI：0.923~0.980）。其中神经/其他系统疾病亚组的患儿ROC曲线下面积为0.768,呼吸/循环系统疾病亚组的患儿ROC曲线下面积为0.968。PEWS评分 > 6分、4~6分及 ≤ 3分患儿的病死率分别为40%、21%、0,组间比较差异有统计学意义（P < 0.001）。结论 PEWS对识别危重症患儿病情严重程度有重要价值,且不同病种对PEWS评分的敏感性有差异;PEWS评分对患儿的预后有预测价值。     

Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children.

OBJECTIVE: To study the association of timing, duration, and intensity of hyperglycemia with pediatric intensive care unit (PICU) mortality in critically ill children. DESIGN: Retrospective cohort study. SETTING: PICU of a university-affiliated, tertiary care, children's hospital. PATIENTS: A total of 152 critically ill children receiving vasoactive infusions or mechanical ventilation. INTERVENTIONS: None. METHODS: With institutional review board approval, we reviewed a cohort of 179 consecutive children, 1 mo to 21 yrs of age, treated with mechanical ventilation or vasoactive infusions. We excluded 18 with <3 microg.kg(-1).min(-1) dopamine only, diabetes, or solid organ transplant and nine who died within 24 hrs of PICU admission. Peak blood glucose (BG) and time to peak BG during PICU admission, duration of hyperglycemia (percentage of PICU days with any BG of >126 mg/dL), and intensity of hyperglycemia (median BG during first 48 PICU hours) were analyzed for association with PICU mortality using chi-square, Student's t-test, and logistic regression. MEASUREMENTS AND MAIN RESULTS: Peak BG of >126 mg/dL occurred in 86% of patients. Compared with survivors, nonsurvivors had higher peak BG (311 +/- 115 vs. 205 +/- 80 mg/dL, p <.001). Median time to peak BG was similar in nonsurvivors (23.5 hrs; interquartile ratio, 5-236 hrs) and survivors (19 hrs; interquartile ratio, 6-113 hrs). Duration of hyperglycemia was longer in nonsurvivors (71% +/- 14% of PICU days) vs. survivors (37% +/- 5% of PICU days, p <.001). Nonsurvivors had more intense hyperglycemia during the first 48 hrs in the PICU (126 +/- 38 mg/dL) vs. survivors (116 +/- 34 mg/dL, p <.05). Univariate logistic regression analysis showed that peak BG and the duration and intensity of hyperglycemia were each associated with PICU mortality (p <.05). Multivariate modeling controlling for age and Pediatric Risk of Mortality scores showed independent association of peak BG and duration of hyperglycemia with PICU mortality (p <.05). CONCLUSIONS: Hyperglycemia is common in critically ill children. Peak BG and duration of hyperglycemia are independently associated with mortality in our PICU. A prospective, randomized trial of strict glycemic control in this subset of critically ill children who are at high risk of mortality is both warranted and feasible.     

动态监测血乳酸与小儿危重病例评分的相关性

目的 探讨动态监测PICU患儿血乳酸与小儿危重病例评分(PCIS)的相关性.方法 对77例入住南通大学附属常州儿童医院儿科重症监护病房的患儿立即进行PCIS,根据评分结果分为极危重组(23例)、危重组(32例)、非危重组(22例).并检测患儿动脉血乳酸水平,每6 h监测1次,并测出乳酸峰值.比较各组间乳酸监测指标(入PICU乳酸水平、乳酸峰值)和PCIS,进行相关性分析,探讨其与患儿预后的相关性.结果 极危重组血乳酸水平:入PICU时乳酸[(5.28±3.69) mmol·L-1]、乳酸峰值[(8.54±4.32) mmol·L-1]明显高于危重组和非危重组(F=3.98,3.12,Pa<0.01),而PCIS[(65.79±2.34) 分]明显低于其他2组(F=4.23,P<0.01);死亡组 PCIS[(62.35±4.22) 分]低于存活组[(89.21±5.36) 分](t=3.15,P<0.01),而血乳酸水平[(5.31±4.05) mmol·L-1]高于存活组[(3.22±2.13) mmol·L-1](t=2.32,P<0.05);PCIS与血乳酸水平呈负相关(r=-0.889,P<0.01).结论 血乳酸升高的PICU危重患儿病情更重、预后更差,PCIS评分可有效评估患儿的病情和预后,并与乳酸水平存在显著负相关.动态监测血乳酸水平是反映危重病患儿病情严重程度和预测患儿转归的较好指标.     

脓毒症患儿血清白蛋白水平与预后的相关性分析

目的 探讨脓毒症患儿血清白蛋白水平与其病情严重程度和预后的相关性。方法 回顾性收集2010年2～7月在湖南省儿童医院PICU住院诊断为脓毒症的连续病例的病史资料,提取一般情况、临床表现、实验室检查指标、疾病严重程度和预后等资料。依据入住PICU 24 h内的血清白蛋白水平分为重度低白蛋白血症组（≤25 g·L-1）,中度低白蛋白血症组（～30 g·L-1）,轻度低白蛋白血症组（～35 g·L-1）和正常白蛋白组（>35 g·L-1）。分析血清白蛋白水平与脓毒症患儿的临床表现、实验室指标、疾病严重程度和预后的相关性。采用Logistic回归分析血清白蛋白水平和预后的相关性。结果 符合脓毒症诊断标准的212例患儿进入分析,其中重度低白蛋白血症组24例,中度低白蛋白血症组50例,轻度低白蛋白血症组61例,正常白蛋白组77例。①重度低白蛋白血症组腹泻、腹胀、肠鸣音减弱、应激性溃疡、水肿和脏器功能衰竭数量>3个的发生率显著增高（P<0.05）。②随着血清白蛋白水平的降低, WBC计数、CRP≥8 mg·L-1和PCT＞2 mg·L-1的发生率呈升高趋势（P<0.05）;血糖≥6.7 mmol·L-1的发生率和乳酸水平呈升高趋势（P<0.05）。③随着血清白蛋白水平的降低,PRISM Ⅲ评分、严重脓毒症和脓毒性休克发生率呈升高趋势（P<0.05）,PICS评分呈下降趋势（P<0.05）。④多因素Logistic回归分析结果显示,严重脓毒症和脓毒性休克、重度低白蛋白血症、PRISMⅢ评分≥8分是脓毒症患儿死亡的危险因素,OR值(95%CI)分别为8.20（1.33～18.96）、2.85（1.34～10.73）和1.22（1.02～15.78）。⑤存活患儿第1、3和7天血清白蛋白水平呈升高趋势,且显著高于死亡患儿。结论 血清白蛋白水平与炎症感染指标的相关性较好,血清白蛋白水平≤25 g·L-1可作为脓毒症患儿死亡的危险因素。     

危重患儿血糖与胰岛素水平的临床分析

目的 分析危重患儿血糖和胰岛素水平变化,探讨危重患儿高血糖发生相关机制.方法 检测2007年1至12月我院PICU收治的51例危重患儿入院时血糖和胰岛素水平变化,并与15例健康体检儿检测结果进行对照分析.结果 (1)各种基础疾病下的危重患儿入院24 h内血糖均值均高于正常范围,以感染性休克组为最高[(11.35±6.21)mmol/L];患儿入院5 d内每日血糖均值波动情况以入院当天为最高,其后持续高于正常.(2)人院24 h内肺部感染、颅内感染和感染性休克患儿血胰岛素水平分别为(17.65±16.85)mU/L、(13.45±7.33)mU/L、(16.24±12.41)mU/L,均高于对照组[(8.70±6.57)mU/L],而先天性心脏病组[(6.75±3.22)mU/L]略低于正常组,但各组间差异无显著性(F=0.356,P=0.127);入院当天和第3天、第5天患儿血胰岛素平均水平均高于正常对照组[(8.70±6.57)mU/L];根据血糖水平,将患儿分为血糖正常组和高血糖组,两组血胰岛素水平分别为(5.44±3.38)mU/L、(14.22±12.29)mU/L,高血糖组胰岛素水平明显高于对照组.(3)患儿危重评分(PIM Ⅱ)均值为12.69±16.82,共死亡8例,病死率为15.6%;死亡患儿血糖和胰岛素水平均明显高于存活患儿(P＜0.05).(4)血糖和血胰岛素水平间无明显线性关系;危重症评分和血胰岛素水平无线性相关性;血糖和危重症评分间线性相关性不显著.结论 危重症患儿常出现高血糖和高胰岛素血症,两者在一定程度上间接反映疾病严重程度,也是判断预后的间接指标;高血糖与胰岛素相对不足或(和)胰岛素抵抗有关,至于其确切的关系需要进一步研究证实.     

Serum insulin-like growth factor 1 and growth hormone levels of hypoxic-ischemic newborns

A number of growth factors, their binding proteins, and their receptors have been shown to be induced in the hypoxic-ischemic (HI) brain. In this prospective study, we aimed at determining the levels of insulin-like growth factor 1 (IGF-1), growth hormone (GH), and cortisol in HI babies and at identifying whether they differ from the levels of control infants. The serum IGF-1 levels were measured after the first 12-24 h of life, and the measurements were repeated on the 5th and 10th days of life for babies with HI encephalopathy (n = 18) and on the 10th day of life for controls (n = 19). Blood samples for measurement of cortisol and GH from both HI and control groups were collected after the first 12-24 h of life. There were 11 babies in the mild-to-moderate (stages I and II) group and 7 babies in the severe (stage III) group according to Sarnat and Sarnat. The IGF-1 levels of the HI group measured after 12-24 h [78.5 +/- 27.9 (range 9-123.4) ng/ml] and on the 10th day [72.2 +/- 36.8 (range 29.7-159.2) ng/ml] of life were statistically significantly lower than the IGF-1 levels of the control group [121.5 +/- 50.4 (range 74.4-280.5) ng/ml and 133.1 +/- 34.4 (range 65.9-202) ng/ml, respectively] (p = 0.002 and p = 0.001, respectively). But there was no statistically significant difference between mild-to-moderate HI group and severe HI group in terms of IGF-1 levels after 12-24 h and 5 and 10 days of life (p > 0.05). Also there was no statistically significant difference in IGF-1 values after the first 12-24 h and after 10 days of life between HI subjects who died or survived (p > 0.05). The GH levels of the HI group after the first 12-24 h of life [34.6 +/- 32.3 (range 0.1-120) mIU/l] were statistically significantly higher than those in the control group [10.4 +/- 4.5 (range 3.7-16.9) mIU/l] (p = 0.005). There was no statistically significant difference in the serum cortisol levels between HI and control groups after the first 12-24 h of life [18.7 +/- 17.0 (range 1.6-65.1) microg/dl vs. 10.8 +/- 5.4 (range 3.0-23.2) microg/dl] (p > 0.05). No statistically significant correlation was found between IGF-1 levels and GH and cortisol levels of the HI encephalopathy group [r = -0.113 (p > 0.05) and r = 0.108 (p > 0.05), respectively]. In conclusion, this study showed decreased levels of serum IGF-1 and increased levels of GH which may be secondary to serum IGF-1 influx from the circulation to the brain as a protective mechanism or may be due to some cytokines which alter the GH/IGF axis, inhibit the action of IGF-1, and stimulate IGF-binding protein 1.     

Low dose of insulin for assessment of growth hormone and cortisol release in short children

OBJECTIVE: In 55 prepubertal children with growth failure, aged 8.62 +/- 2.89 years, we evaluated the efficacy of a test using only half the usual dose of insulin by comparing the results with those obtained during a classical arginine tolerance test, performed separately. PATIENTS AND METHODS: The patients were randomly divided into two groups: group A consisting of 37 children received 0.05 U/kg insulin, while group B consisting of 18 patients received 0.1 U/kg insulin. Each child received the same dose of arginine per kg during the second test. RESULTS: Serum growth hormone (GH) peak levels were significantly (p < 0.01) lower in children of group A (6.59 +/- 4.10 ng/ml) than in those of group B (10.12 +/- 5.80 ng/ml). No differences of GH peak levels were found in patients of the two groups after arginine infusion. The injection of 0.05 U/kg insulin induced a significantly (p < 0.0001) lower percent decrease of serum glucose than 0.1 U/kg. No difference of the percent increase of serum cortisol induced by insulin at 0.05 U/kg and 0.1 U/kg was observed. CONCLUSION: The diagnosis of GH deficiency in children can be supported by a blunted GH response after two or more pharmacological stimuli including hypoglycaemia induced by only half the usual dose of insulin.     

血清生长激素和胰岛素样生长因子-Ⅰ在危重症中的变化及临床意义

目的 探讨血清生长激素（growth hormone,GH）和胰岛素样生长因子-Ⅰ （insulin like growth factor-Ⅰ,IGF-Ⅰ）在危重症患儿中的变化及其临床意义.方法 选择2009年1月至2012年1月同期入住PICU的脓毒症患儿42例为脓毒症组,先天性心脏病择期在体外循环下行开胸手术治疗后的患儿20例为术后组,检测入院次日及手术后次日晨血清GH和IGF-Ⅰ水平,选择健康体检儿童60例为对照组,比较组间GH、IGF-Ⅰ水平的变化.结果 脓毒症组GH水平为（6.71±6.62） ng/ml,术后组GH水平为（8.86±8.06） ng/ml,,两者均显著高于对照组（3.87±3.31） ng/ml,差异有统计学意义（P＜0.05）,而脓毒症组与术后组之间差异无统计学意义;脓毒症组IGF-Ⅰ水平为（63.72±54.17） ng/ml,与术后组（119.06±102.12） ng/ml和健康对照组（154.22±107.10） ng/ml比较,显著降低,差异有统计学意义（P＜0.05）,术后组与对照组比较差异无统计学意义;脓毒症组内存活者与死亡者比较GH无统计学意义差异,IGF-Ⅰ水平显著降低（P＜0.05）.结论 危重症时GH水平升高对机体应激具有积极作用;脓毒症时IGF-Ⅰ水平显著降低,可作为反映重症感染存在的较灵敏指标,并有助于判断预后.     

窒息新生儿血糖、皮质醇、胰岛素水平变化及其临床意义

目的观察窒息新生儿血糖（BG）、皮质醇（Co）、胰岛素（InS）水平变化，以探讨其临床意思。方法用微量法和放免法检测40例正常新生儿和50例窒息新生儿血糖、皮质醇、胰岛素。结果窒息新生儿脐血BG、InS、Co明显升高，且与窒息严重程度呈正相关（r值分别为0．36、0．31、0．33）。出生3dBG和Co水平有所降低，而InS水平无降低趋势。重度窒息组与对照组相比，各项水平差异显著（P〈0．01），且窒息组3d时BG、Co水平与脐血相比有明显差异（P〈0．05）。结论应激状态可造成BG、InS、Co升高，随窒息解除、病情缓解，胰岛素抵抗的恢复较血糖和皮质醇恢复慢。在窒息抢救时，尤其是重度窒息儿，应密切监测血糖与激素变化，且慎用糖皮质激素。     

Small for gestational age (SGA): endocrine and metabolic consequences and effects of growth hormone treatment

Several studies have demonstrated an association between low birth weight and impaired insulin sensitivity or even type 2 diabetes mellitus (DM2) in later life. Growth hormone (GH) is known to increase fasting and postprandial insulin levels. For that reason concern has been expressed regarding possible detrimental effects of GH therapy in children born SGA. In a Dutch trial the possible side effects of GH therapy on carbohydrate metabolism were assessed in short children born SGA after 6 years and at 6 months after discontinuation of GH therapy. This study included 79 prepubertal short children born SGA, participating in a multicenter double-blind, randomized, dose-response GH trial. Inclusion criteria were: 1) birth length SDS below -1.88, 2) age 3-11 years in boys and 3-9 years in girls, 3) height SDS < -1.88, 4) no spontaneous catch-up growth, and 5) an uncomplicated neonatal period. Mean (SD) value for age was 7.3 (2.1) years, birth length SDS -3.6, height SDS -3.0 (0.7) and BMI SDS -1.2 (1.3). All children were randomly assigned to either group A (n = 41) using 1 mg GH/m2/day or group B (n = 38) using 2 mg/m2/ d/ay (approximately 0.1 or 0.2 IU/kg/d, respectively). Standard oral glucose tolerance tests (OGTTs) were performed before and during 6 years of GH therapy and 6 months after discontinuation of GH therapy. Before GH therapy 8% of the children had impaired glucose tolerance (IGT) according to criteria of the WHO. After 6 years of GH therapy, IGT was found in 4% and after stopping GH in 10%. Mean fasting glucose increased significantly with 0.5 mMol/l after 1 year of GH therapy, without a further increase thereafter. GH therapy induced considerably higher fasting and glucose-stimulated insulin levels. None of the observed changes were different between the GH dosage groups. Children who remained prepubertal had similar glucose and insulin levels compared to children who entered puberty. HbA1c levels were always in the normal range and none of the children developed diabetes mellitus. After discontinuation of GH therapy the mean serum glucose levels remained normal and the mean serum insulin levels decreased significantly, to normal age reference values. Before the start of GH the mean systolic blood pressure was significantly higher compared to age-matched peers, whereas during GH therapy a significant decline in mean systolic blood pressure occurred, which remained similar after discontinuation of GH treatment. In conclusion, continuous, long-term GH therapy in short children born SGA has no adverse effects on glucose levels, even with GH dosages up to 2 mg/m2/day. However, as has been reported in other patient groups, GH induced higher fasting and glucose-stimulated insulin levels, indicating insulin resistance. After discontinuation of GH, serum insulin levels declined to normal age-matched reference levels. Since impaired insulin sensitivity and DM2 have been demonstrated in relatively young patients born SGA, long-term follow-up of children born SGA is advised, also after discontinuation of GH therapy.     

Activity of the growth hormone/insulin-like growth factor-I axis in critically ill children

Critical illness has an important impact on the human endocrine system. Very few studies have been performed to elucidate the alterations of the GH/IGF-I axis in acutely ill children. The aim of this study was to investigate several parameters of this axis in children with trauma (TRA) and sepsis (SEP) requiring admission to the pediatric intensive care unit (PICU). A total of 16 children, ten with TRA and six with SEP (age 1-10 years) as well as 18 healthy children (CS) of similar age and gender were included in the study. Two children, one with TRA and one with SEP, died. Serum IGF-I and -II, IGFBP-1 and -3, and GH levels were measured on days 1, 3 and 7 after admission. GH levels were higher in the patients than in CS (p = 0.04), with no difference between TRA and SEP, and were elevated during PICU stay (p = 0.05). Serum IGF-I, -II and IGFBP-3 were lower in the patients than in CS (p = 0.03, 0.02 and 0.001, respectively) with a tendency to increase up to day 7. Finally, IGFBP-1 levels were similar in the patients and CS. These findings indicate that critically ill children are characterized by low levels of IGF-I and -II as well as IGFBP-3 accompanied by elevated levels of GH, probably reflecting the development of peripheral GH resistance. No significant differences were found between the different catabolic conditions, sepsis and trauma.