儿童急性淋巴细胞白血病中E-钙黏蛋白甲基化对预后的影响

目的 通过Meta分析探讨在儿童及青少年成熟B细胞非霍奇金淋巴瘤治疗中应用利妥昔单抗联合化疗的疗效与安全性,为更加合理地应用利妥昔单抗提供理论依据。 方法 检索PubMed、Embase、Cochrane Library、ClinicalTrials.gov、Web of Science、中国知网、万方、维普数据库的文献,共筛选出从建库至2022年6月公开发表的利妥昔单抗治疗儿童及青少年成熟B细胞非霍奇金淋巴瘤的10篇文献,共计886例患儿。以3年无事件生存率、3年总生存率、完全缓解率、病死率和不良反应发生率作为结局指标,采用RevMan 5.4软件进行Meta分析、亚组分析、敏感性分析和发表偏倚分析。 结果 与单纯化疗组相比,利妥昔单抗联合化疗组3年无事件生存率显著提高（HR=0.38,95%CI：0.25~0.59,P<0.001）,3年总生存率显著提高（HR=0.29,95%CI：0.14~0.61,P=0.001）,完全缓解率显著提高（OR=3.72,95%CI：1.89~7.33,P<0.001）,病死率显著降低（OR=0.31,95%CI：0.17~0.57,P<0.001）。而两组的不良反应发生率差异无统计学意义（OR=1.28,95%CI：0.85~1.92,P=0.24）。 结论 在儿童及青少年成熟B细胞非霍奇金淋巴瘤治疗方案中添加利妥昔单抗可带来明显的生存益处,且不会增加不良反应的发生。     

重症监护室患儿心脏停搏后早期出现急性肾损伤的危险因素及预后分析

目的 探讨心脏停搏（cardiac arrest,CA）患儿发生急性肾损伤（acute kidney injury,AKI）的相关因素及预后的影响因素。 方法 回顾性收集2016年6月—2021年6月湖南省儿童医院儿童重症监护室发生CA患儿的病历资料。按CA恢复自发循环（return of spontaneous circulation,ROSC）48 h内是否发生AKI分为AKI组（n=50）和非AKI组（n=113）,AKI组按ROSC 7 d时预后情况分为存活组（n=21）和死亡组（n=29）。采用多因素logistic回归分析CA患儿早期发生AKI的相关因素及预后影响因素。 结果 CA后AKI发生率为30.7%（50/163）。AKI组7 d及28 d病死率分别为58.0%（29/50）、78.0%（39/50）,非AKI组为31.9%（36/113）、58.4%（66/113）。多因素logistic回归分析显示,心肺复苏时间长（OR=1.164,95%CI：1.088~1.246,P<0.001）、基线血清白蛋白低（OR=0.879,95%CI：0.806~0.958,P=0.003）、CA前应用肾上腺素（OR=2.791,95%CI：1.119~6.961,P=0.028）与CA后AKI发生密切相关;基线小儿危重病例评分低（OR=0.761,95%CI：0.612~0.945,P=0.014）、CA前应用肾上腺素（OR=7.018,95%CI：1.196~41.188,P=0.031）、CA前机械通气（OR=7.875,95%CI：1.358~45.672,P=0.021）与CA后AKI患儿死亡密切相关。 结论 CA后ROSC患儿应密切监测血清白蛋白,尤其是心肺复苏时间长、基线小儿危重病例评分低、CA前应用肾上腺素、CA前机械通气者应及早识别和干预,以降低AKI发生率和病死率。     

儿童嗜酸性粒细胞性胃肠炎糖皮质激素治疗的预测因素分析

目的 分析儿童嗜酸性粒细胞性胃肠炎临床特点和治疗方案的关系，探讨糖皮质激素治疗的适用情况，为儿科医师选择治疗方案提供依据。 方法 回顾性收集广州市妇女儿童医疗中心2012年1月至2020年12月收治的182例嗜酸性粒细胞性胃肠炎患儿的临床资料。根据治疗方案中是否使用糖皮质激素分为激素组和对照组，比较分析两组患儿年龄、过敏史、临床症状、实验室检查结果、内镜下表现和胃肠黏膜病理结果，对差异有统计学意义的结果进一步行logistic回归分析。 结果 182例患儿中，36例使用糖皮质激素治疗，占总人数的19.8%。激素组患儿出现血便、贫血，内镜下出现黏膜溃疡/管腔狭窄的比例，以及黏膜嗜酸性粒细胞浸润计数均明显高于对照组（n=146，P<0.05）；激素组血清白蛋白水平明显低于对照组（P<0.05）。多因素logistic回归分析结果显示，内镜下见黏膜溃疡/管腔狭窄（OR=10.830，95%CI：3.090~37.961，P<0.001）和黏膜嗜酸性粒细胞浸润计数升高（OR=0.967，95%CI：0.941~0.993，P=0.015）可提示使用糖皮质激素治疗儿童嗜酸性粒细胞性胃肠炎。 结论 内镜下见到黏膜溃疡/管腔狭窄，病理显示黏膜嗜酸性粒细胞浸润计数明显升高，均提示儿童嗜酸性粒细胞性胃肠炎的治疗方案中可采用糖皮质激素治疗。 引用格式:     

儿童造血干细胞移植后急性肾损伤相关危险因素的回顾性研究

目的 探讨造血干细胞移植（hematopoietic stem cell transplantation,HSCT）后急性肾损伤（acute kidney injury,AKI）的危险因素。 方法 回顾性研究2018年1月至2020年1月111例行HSCT患儿的临床资料。采用多因素logistic回归分析筛选出AKI发生的影响因素;采用Kaplan-Meier生存分析比较不同级别AKI患儿生存预后差异。 结果 111例HSCT患儿中,AKI发生率为52.3%（58/111）。移植物抗宿主病（Ⅱ~Ⅳ度）（OR=4.406,95%CI：1.501~12.933,P=0.007）、肝小静脉闭塞综合征（OR=4.190,95%CI：1.191~14.740,P=0.026）、血栓性微血管病（OR=10.441,95%CI：1.148~94.995,P=0.037）与HSCT患儿移植后AKI发生密切相关。AKI Ⅲ期患儿的1年生存率（28.6%±12.1%）低于NAKI（82.8%±5.2%）、AKI Ⅰ期（81.7%±7.4%）、AKI Ⅱ期（68.8%±11.6%）患儿（P<0.05）。 结论 患儿HSCT后发生Ⅲ期AKI具有较高的病死率;移植物抗宿主病、肝小静脉闭塞综合征、血栓性微血管病与HSCT后AKI发生密切相关。     

运动康复训练对支气管哮喘儿童运动能力和生活质量干预效果的系统评价

目的 系统评价运动康复训练对支气管哮喘儿童运动能力和生活质量的干预效果。 方法 检索PubMed、Cochrane Library、Web of Science、EBSCO、中国知网、维普数据库、万方数据库等数据库从建库至2021年2月关于运动康复训练对支气管哮喘儿童影响的随机对照试验。采用RevMan 5.3软件进行Meta分析。 结果 共纳入14项研究,共计990例受试者。Meta分析结果显示：（1）运动康复组运动能力优于常规治疗组：6 min步行试验的步行距离（MD=108.13,P<0.01）、自我疲劳感觉值（MD=-2.16,P<0.001）、峰值功率（MD=0.94,P=0.001）均显著优于常规治疗组;（2）在儿科哮喘生活质量问卷中,运动康复组生活质量总评分（SMD=1.28,P=0.0002）显著高于常规治疗组,活动受限评分（SMD=1.38,P=0.0002）、症状评分（SMD=1.02,P<0.001）、情感功能评分（SMD=0.86,P<0.001）均显著高于常规治疗组。 结论 运动康复训练对支气管哮喘儿童运动能力和生活质量具有一定的改善作用,但受纳入研究数量和质量的限制,作为指导临床应用还需进一步研究和验证。     

青少年抑郁情绪及自杀意念与父母教养方式之间的关联研究

目的 研究青少年抑郁情绪及自杀意念与父母教养方式之间的关系。 方法 采用整群抽样法,于2014~2018年抽取河南省新乡市6 195名初高中生进行调查研究。调查工具包括一般社会资料问卷、父母教养方式问卷及Kutcher青少年抑郁量表（11项）。采用多因素logistic回归分析评估青少年抑郁情绪及自杀意念与父母教养方式之间的关联。 结果 有效问卷为6 194份,其中男性2 586名（41.75%）,女性3 608（58.25%）;年龄（16.4±1.9）岁（范围：11~20岁）。在6 194名青少年中,1 333名（21.52%）青少年有抑郁情绪,508名（8.20%）青少年有自杀意念。青少年的抑郁情绪与母亲的控制（OR=1.059,P<0.001）和父亲的控制呈明显正关联（OR=1.061,P<0.001）,而与母亲的关爱（OR=0.937,P<0.001）和父亲的关爱（OR=0.917,P<0.001）呈明显负关联。青少年的自杀意念与母亲的控制（OR=1.110,P<0.001）和父亲的控制（OR=1.076,P<0.001）呈明显正关联,而与母亲的关爱（OR=0.895,P<0.001）和父亲的关爱（OR=0.914,P<0.001）呈明显负关联。 结论 父母的关爱可降低青少年抑郁情绪的发生风险,而父母控制性可增加青少年抑郁情绪及自杀意念的发生风险。 引用格式:     

窒息新生儿糖代谢紊乱对近期预后的影响：一项湖北省多中心研究

目的 分析窒息新生儿糖代谢紊乱对近期预后的影响。 方法 回顾性纳入湖北省52家医院2018年1~12月收治的生后12 h内有血糖数据的窒息患儿,收集病历资料及生后1、2、6、12 h的血糖数据,允许时间误差为0.5 h。根据住院期间是否诊断脑损伤和/或死亡分为预后不良组（693例）及预后良好组（779例）。分析两组患儿生后12 h内糖代谢紊乱情况及其对近期预后的影响。 结果 预后不良组中来自二级医院（48.5% vs 42.6%）、重度窒息（19.8% vs 8.1%）、亚低温治疗（4.8% vs 1.5%）的比例及糖代谢紊乱发生率（18.8% vs 12.5%）均高于预后良好组（P<0.05）;预后不良组生后1、2、6 h糖代谢紊乱发生率均高于预后良好组（P<0.05）。多因素logistic回归分析显示,反复高血糖为窒息患儿预后不良的独立危险因素（校正后OR=2.380,95%CI：1.275~4.442,P<0.05）。 结论 窒息患儿合并反复高血糖可能提示近期预后不良,应加强对该类患儿的早期神经系统监测与管理。     

MTHFR基因多态性与儿童支气管哮喘易感性及糖皮质激素疗效的相关性

目的 探讨亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）基因多态性与儿童支气管哮喘易感性及糖皮质激素（glucocorticoid,GC）疗效的相关性。 方法 选取2018年6月至2020年12月住院治疗的儿童支气管哮喘患儿173例为观察组,均接受GC雾化吸入治疗,连续3个月。选取同期体检的健康儿童178例为对照组。采用PCR检测两组受试儿MTHFR基因C677T位点的基因型,分析两组基因型分布差异性;比较观察组不同基因型患儿治疗前后血清免疫球蛋白E、白细胞介素-8（interleukin-8,IL-8）、白三烯B4（leukotriene B4,LTB4）水平,肺功能指标差异及临床疗效差异。 结果 与对照组相比,观察组TT基因型及T等位基因频率均显著升高（P<0.001）;TT/CT基因型及T等位基因是支气管哮喘易感性的独立危险因素（OR分别为6.615、7.055,P<0.001）。GC治疗后3种基因型患儿免疫球蛋白E、IL-8和LTB4水平较治疗前显著降低,第1秒用力呼气容积（forced expiratory volume in 1 second,FEV1）、用力肺活量（forced vital capacity,FVC）、FEV1/FVC%较治疗前显著升高（P<0.001）;TT基因型患儿IL-8和LTB4水平显著低于CC基因型患儿,LTB4水平明显低于CT基因型患儿,TT基因型患儿FVC明显高于CT基因型患儿,FEV1/FVC%显著高于CC基因型患儿（P<0.05）;治疗后3种基因型患儿临床GC治疗疗效比较差异有统计学意义,其中TT基因型患儿GC疗效良好比例显著高于CC基因型患儿（P<0.05）,且TT基因型是GC疗效良好的独立影响因素（OR=2.111,P=0.018）。 结论 MTHFR基因多态性与儿童哮喘易感性及GC疗效相关,携带TT/CT基因型儿童支气管哮喘发病风险更高,TT基因型对GC治疗具有更高的敏感性。     

儿童哮喘管理与哮喘控制水平的临床研究

目的 探索家庭结构对青少年抑郁、焦虑症状的影响及其作用机制。 方法 采用整群抽样法于2021年4—5月对上海市7所中学的学生进行线上问卷调查。问卷包括自编一般情况调查表、儿童期创伤问卷、儿童抑郁量表和儿童焦虑性情绪障碍筛查表。采用单因素方差分析、卡方检验、二元logistic回归、中介效应分析等方法探讨不同家庭结构青少年的抑郁和焦虑症状发生情况、儿童期创伤的差异及其中介作用。 结果 与核心家庭青少年相比,三代直系家庭的青少年出现抑郁症状的风险较低（OR=0.794,95%CI：0.649~0.972,P<0.05）,寄宿家庭的青少年出现抑郁症状的风险较高（OR=4.548,95%CI：1.113~18.580,P<0.05）;隔代家庭和寄宿家庭的青少年在儿童期创伤问卷中情感忽视维度的得分更高（P<0.05）。情感忽视在隔代家庭和寄宿家庭对青少年抑郁症状的影响中起中介作用。 结论 父母和祖辈在家庭结构中具有一定的积极影响。与父母分离会使青少年感知到更多的情感忽视,进而增加抑郁症状的发生。     

儿童碳青霉烯类耐药肺炎克雷伯菌医院感染的危险因素分析：单中心配对病例-病例-对照研究

目的 调查儿童专科医院住院患儿碳青霉烯类耐药肺炎克雷伯菌（carbapenem-resistant Klebsiella pneumonia,CRKP）感染及死亡的危险因素,为该类细菌的感染防治提供参考依据。 方法 采用配对病例-病例-对照研究的方法。回顾性纳入昆明市儿童医院2019年1月至2021年10月的81例CRKP感染患儿,81例碳青霉烯类敏感肺炎克雷伯菌（carbapenem-sensitive Klebsiella pneumonia,CSKP）感染患儿,及162例对照儿童（住院期间未分离出CRKP及CSKP的患儿）,比较分析各组儿童的基础疾病、既往住院暴露及该次住院暴露情况与CRKP感染及死亡的关联性。 结果 与对照组比较,既往3个月内有住院史与CRKP、CSKP感染存在较高关联强度（分别OR=14.25、10.07,P<0.01）;CRKP感染患儿特异的危险因素包括既往3个月内有碳青霉烯药物治疗史（OR=16.54,P<0.01）及该次住院接受中心静脉置管（OR=33.03,P<0.01）。而既往3个月内有碳青霉烯药物治疗史（OR=28.33,P<0.01）及该次住院抗生素经验性用药（OR=14.50,P<0.01）是导致CRKP患儿死亡的危险因素。 结论 患儿既往3个月内有住院史、碳青霉烯类药物治疗史,以及入院后接受侵入性操作是影响CRKP感染及预后的主要原因。儿童专科医院有必要开展入院时CRKP主动筛查,规范使用抗生素,并加强医院感染监测,以控制CRKP感染的发生。 ［中国当代儿科杂志,2022,24（9）：1008-1013］     

促性腺激素释放激素类似物在儿童中枢性性早熟中的应用

促性腺激素释放激素(GnRH)依赖性性早熟/中枢性性早熟(GDPP/CPP)是儿科内分泌系统的常见病之一,促性腺激素释放激素类似物(GnRHa)是国际上治疗CPP的主要药物,其通过抑制下丘脑-垂体-性腺轴的活动和性激素分泌,减缓CPP患儿骨龄进展、改善成年身高。在临床实践中,仍需要不断探索GnRHa治疗的获益人群,探讨GnRHa的最佳治疗方案,不断完善GnRHa长期疗效和安全性证据。     

中枢性性早熟对儿童体格及性发育的影响

中枢性性早熟（CPP）是一种青春期发育异常,表现为第二性征提前、骨格成熟和体格提前发育,最终影响儿童的成年身高,甚至可能会产生如恐惧、不安等心理行为问题。目前国际上公认治疗最好的药物为促性腺激素释放激素类似物（GnRHa）,其主要目的是改善儿童的最终成年身高;但与此同时,其对患儿的生长发育也存在一些不良反应。该文就CPP及GnRHa治疗对儿童体格及性发育的影响作一综述,以引起临床医师对此疾病及其安全用药的关注。     

GnRHa治疗中枢性性早熟女童对终身高的影响

目的：观察促性腺激素释放激素类似物（GnRHa）对治疗中枢性性早熟（central precocious puberty,CPP）女童终身高的作用及相关因素。方法：对26例CPP女童应用GnRHa治疗前后预测身高、骨龄的标准差分值［HtSDS(BA)］、终身高、体重指数（BMI）、初潮情况等进行评价,分析它们与终身高的相关性。结果：治疗前预测身高为151.5±5.7 cm;停药时预测身高为158.4±5.2 cm;终身高为158.0±4.0 cm,高于靶身高155.3±4.4 cm (P<0.01)。终身高与初始身高、预测身高、HtSDS(BA)正相关。治疗前BMI为17.1±2.1、治疗后BMI为19.9±3.2,两者呈正相关。停药后平均13.2±6.1个月后初潮,平均初潮年龄为12.2±0.7岁。结论：GnRHa治疗CPP可有效地改善终身高,终身高与治疗前身高及预测身高等密切相关,停药后患儿青春发育与正常儿童相似。［中国当代儿科杂志,2009,11（5）：374-376］     

Combined therapy with GnRH analog plus growth hormone in central precocious puberty

GnRH analogues (GnRHa) arrest pubertal development, and slow growth velocity (GV) and bone maturation, thus improving adult height in central precocious puberty (CPP). In some patients, however, GV decreases to such an extent that it compromises the improvement in predicted adult height (PAH) and therefore the addition of GH is suggested. Of 20 patients with idiopathic CPP (treated with GnRHa [depot-triptorelin] at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 yr) whose GV fell below the 25th percentile for chronological age (CA), ten received, in addition to the GnRHa, GH at a dose of 0.3 mg/kg/wk, s.c. 6 days weekly, for 2-4 yr. Ten patients matched for BA, CA, and duration of GnRHa treatment who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of the addition of GH. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 yr in GnRHa + GH vs 13.0 +/- 0.1 yr in the control group. At the conclusion of the study all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH + GnRHa showed an adult height significantly higher (p<0.001) than pretreatment PAH (160.6 +/- 1.3 vs 152.7 +/- 1.7 cm). Height SDS for BA significantly increased from -1.5 +/- 0.2 at start of GnRHa to -0.21 +/- 0.2 at adult height (p<0.001). Target height was significantly exceeded. The GnRH alone treated group reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs 155.5 +/- 1.9 cm). Height SDS for BA did not change (from -1.0 +/- 0.3 at start of GnRHa to -0.7 +/- 0.4 at adult height). Target height was just reached but not significantly exceeded. The gain in centimeters obtained calculated between pretreatment PAH and final height was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRH analogue while in patients treated with GnRH analogue alone the gain was just 1.6 cm +/- 1.2 (p=0.001). Furthermore, no side effects, bone age progression, or ovarian cysts, were observed in GnRHa + GH treated patients. In conclusion, a gain of 7.9 cm in adult height represents a significant improvement which justifies the addition of GH for 2-3 yr to conventional treatment with GnRH analogues in patients with central precocious puberty, and with a decrease in growth velocity so marked as to impair predicted adult height to below the third percentile.     

促性腺激素释放激素类似物对特发性中枢性性早熟女童体重指数影响的长期观察

目的：动态研究促性腺激素释放激素类似物（GnRHa）治疗对特发性中枢性性早熟（ICPP）女童体重指数（BMI）的影响。方法：对2003年1月至2006年1月确诊为ICPP 的134例女童进行随访研究,其中57例给予GnRHa治疗（疗程1.69±0.43年）,测量治疗前、治疗结束时及近成年身高时的身高、体重、骨龄及BMI等,并与未治疗组（77例）比较。结果：（1）GnRHa治疗组在治疗结束时的预测终身高标准差分值（SDS）较治疗前明显升高（P0.05）,且近成年身高SDS明显高于靶身高SDS（P0.05）;近成年身高时的BMI SDS比治疗前和未治疗组明显降低（P<0.01）,但治疗前、治疗结束时及近成年身高时BMI平均值都在±1SD内,处于正常范围。结论：GnRHa对改善ICPP女童终身高有显著疗效;GnRHa治疗后的BMI改变处于正常范围。     

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

OBJECTIVE: To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. PATIENTS: 31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were treated for a mean (SD) of 3.4 (1.0) years and were followed up for 4.0 (1.2) years after the treatment was stopped. RESULTS: The rate of bone maturation decreased during treatment and the predicted adult height increased from 158.2 (7.4) cm to 163.9 (7.5) cm at the end of treatment (p < 0.001). When treatment was stopped bone maturation accelerated, resulting in a final height of 161.6 (7.0) cm, which was higher than the predicted adult height at the start of treatment (p < 0.001). Height at the start of treatment was the most important factor positively influencing final height (r = 0.75, p < 0.001). Bone age at cessation of treatment negatively influenced final height (r = -0.52, p = 0.03). A negative correlation between bone age and height increment after discontinuation of treatment was observed (r = -0.85, p = 0.001). Residual growth capacity was optimal when bone age on cessation of treatment was 12 to 12.5 years. Body mass index increased during treatment and remained high on cessation. At final height, the ratio of sitting height to subischial leg length was normal. Menarche occurred at 12.3 (1.1) years, and at a median (range) of 1.1 (0.4 to 2.6) years after treatment was stopped. The ovaries were normal on pelvic ultrasonography. CONCLUSIONS: Treatment of CPP with triptorelin increases final height, with normal body proportions, and seems to increase body mass index. The best results were achieved in girls who were taller at the start of treatment. Puberty was resumed after treatment, without the occurrence of polycystic ovaries.     

下丘脑-垂体-性腺轴抑制程度对中枢性性早熟女童成年预测身高的影响

目的 研究促性腺激素释放激素类似物(GnRHa)治疗过程中下丘脑-垂体-性腺轴(HPGA)抑制程度与中枢性性早熟(CPP)女童成年预测身高(PAH)的关系,以指导临床个体化调节GnRHa 治疗剂量。方法 收集75 例CPP 女童的临床资料,记录GnRHa 治疗的不同时间点身高、骨龄(BA)、子宫卵巢容积及LH、FSH 峰值、E2 水平,计算各时间点PAH,分析PAH 改善(ΔPAH=PAH-靶身高)的情况及其与HPGA 抑制的关系,并采用阈值效应分析寻找ΔPAH 的最佳HPGA 抑制范围。结果 GnRHa 治疗后PAH 较治疗初期有明显改善。ΔPAH 与ΔBA 呈负相关;治疗24 月时ΔPAH 与LH 呈负相关。将子宫容积控制在2.3~3.0 mL 之间,LH 控制在0.8 IU/L 以下,FSH 控制在2.4 IU/L 以下对延缓BA 的增长及改善PAH 有利。结论 GnRHa 治疗能改善CPP 女童的PAH。选择合适的GnRHa 治疗剂量,将子宫容积、LH、FSH 控制在一定范围内,有利于延缓BA 及改善PAH。     

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist.

OBJECTIVE: To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. PATIENTS: 31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were treated for a mean (SD) of 3.4 (1.0) years and were followed up for 4.0 (1.2) years after the treatment was stopped. RESULTS: The rate of bone maturation decreased during treatment and the predicted adult height increased from 158.2 (7.4) cm to 163.9 (7.5) cm at the end of treatment (p < 0.001). When treatment was stopped bone maturation accelerated, resulting in a final height of 161.6 (7.0) cm, which was higher than the predicted adult height at the start of treatment (p < 0.001). Height at the start of treatment was the most important factor positively influencing final height (r = 0.75, p < 0.001). Bone age at cessation of treatment negatively influenced final height (r = -0.52, p = 0.03). A negative correlation between bone age and height increment after discontinuation of treatment was observed (r = -0.85, p = 0.001). Residual growth capacity was optimal when bone age on cessation of treatment was 12 to 12.5 years. Body mass index increased during treatment and remained high on cessation. At final height, the ratio of sitting height to subischial leg length was normal. Menarche occurred at 12.3 (1.1) years, and at a median (range) of 1.1 (0.4 to 2.6) years after treatment was stopped. The ovaries were normal on pelvic ultrasonography. CONCLUSIONS: Treatment of CPP with triptorelin increases final height, with normal body proportions, and seems to increase body mass index. The best results were achieved in girls who were taller at the start of treatment. Puberty was resumed after treatment, without the occurrence of polycystic ovaries.     

Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution

Out of 35 girls with idiopathic central precocious puberty (CPP) treated with gonadotropin-releasing hormone agonist (GnRHa) (depot-triptorelin) at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 years whose growth velocity fell below the 25th percentile for chronological age (CA), 17 received growth hormone (GH) in addition at a dose of 0.3 mg/kg/week, s.c., 6 days per week, for 2-4 years. The other 18, matched for bone age (BA), CA and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, remained on GnRHa alone, and were used as a control group to evaluate GH efficacy. No patient was GH deficient. Both groups discontinued treatment at a comparable BA (mean +/- SD): BA 13.4 +/- 0.6 in GnRHa plus GH group vs 13.0 +/- 0.5 years in the GnRHa alone group. The 35 patients have reached adult height (i.e. growth during the preceding year was less than 1 cm, with a BA of over 15 years). Patients of the group treated with GH plus GnRHa showed an adult height (161.2 +/- 4.8 cm) significantly higher (p < 0.001) than pre-treatment predicted adult height (PAH) calculated according to tables either for accelerated girls (153.2 +/- 5.0 cm) or for average girls (148.6 +/- 4.3 cm). The adult height of the GnRH alone treated group (156.6 +/- 5.7) was not significantly higher than pre-treatment PAH if calculated on Bayley and Pinneau tables for accelerated girls (153.9 +/- 3.8 cm), whilst it remained significantly higher if calculated on tables for average girls (149.6 +/- 4.0 cm) (p < 0.001). The gain between pre-treatment PAH and final height was 8.2 +/- 4.8 cm according to tables for accelerated girls and 12.7 +/- 4.8 cm according to tables for average girls in patients treated with GH plus GnRHa; while in patients treated with GnRH alone the gain calculated between pre-treatment PAH for accelerated girls was just 2.3 +/- 2.9 cm and 7.1 +/- 2.7 cm greater than pre-treatment PAH for average girls. The difference between the gain obtained in the two groups (about 6 cm) remained the same, however PAH was calculated. The addition of GH to GnRHa in a larger cohort of patients with CPP with a longer follow-up confirms the safety of the combined treatment and the still significant but more variable gain in the group with the combined treatment, probably due to the larger number of patients analyzed. Caution is advised in using such an invasive and expensive treatment, and there is need for further studies before widespread clinical use outside a research setting.     

Gonadotrophin-Releasing Hormone Agonist Treatment of Central Precocious Puberty: an Analysis of Growth Data in a Developmental Context

ABSTRACT. Growth and skeletal maturation was assessed in 83 girls with central precocious puberty (CPP) during pituitary—gonadal suppression induced by treatment with a gonadotrophin-releasing hormone agonist (GnRHa). The mean pretreatment chronological age (CA) was 6.3 years and the mean bone age (BA) was 10.6 years. During the suppression of gonadal sex steroid secretion, mean height velocity (HV) decreased from a pretreatment value of 10.8 cm/year to 5.9 (year 1, n = 83), 4.9 (year 2, n = 72), 4.2 (year 3, n = 49, and 4.4 (year 4, n = 23) cm/year. During each interval, there was a negative correlation between HV and the pretreatment BA. In addition, the rate of skeletal maturation was reduced during GnRHa treatment (ΔBA/ΔCA = 0.6 ± 0.1 over 3 years, n = 45). The rate of skeletal maturation during therapy was also negatively correlated with pretreatment BA. Predicted adult stature, based upon z -scores of height for BA, increased significantly and progressively during therapy but the changes in height SDS for BA varied significantly. Since HV, ΔBA/ΔCA, and the change in height SDS for BA (ΔHT SDS for BA) during pituitary—gonadal suppression all correlated with the initial degree of skeletal maturation, the effect of GnRHa therapy on Final adult height in children with CPP will be best understood if growth data are assessed within a developmental framework.