【作者】 王晨阳；

【导师】 刘世平；

【作者基本信息】 延安大学 ， 儿科学（专业学位）， 2022， 硕士

【摘要】 目的:探讨首次就诊于延安大学附属医院儿科不同性别、不同年龄段、不同类型矮小症患儿血清维生素D营养及分布状况,并研究维生素D在诊断生长激素缺乏症中的价值。方法:选取2019年1月至2022年2月延安大学附属医院儿科首次确诊且符合纳排标准的身材矮小儿童101例。分组如下:1、按性别分为男性组(63例)与女性组(38例);2、按年龄分为学龄前期组(29例)、非学龄期组(72例);3、按病因分为特发性矮小症组(55例)、生长激素缺乏症组(46例)。回顾性调查分析对比各组间一般状况及血清25-羟维生素D(25-(OH)D)水平,进一步探讨各组间矮小症儿童维生素D的营养分布状况,并用单因素二元Logistic回归分析各生长参数和临床指标(如血清维生素D)是否为生长激素缺乏症的独立影响因素,再将得出的独立影响因素进一步作受试者工作曲线(ROC曲线)分析,评价其在诊断生长激素缺乏症方面的价值。结果:根据纳入标准及排除标准,共纳入101名平均年龄在8.8±2.7岁的儿童及青少年,年龄分布范围为3～14岁;矮小症患儿维生素D水平的平均值为15.0±6.7ng/ml,处于不足阶段,其中最低为4.2ng/ml,最高为37.85ng/ml;维生素D缺乏者共42名,占比41.6%,含量为9.1±1.9ng/ml;不足者共39名,占比38.6%,含量为16.3±2.2ng/ml;充足者共19名,占比18.8%,含量为25.5±5.1ng/ml;1、按性别分组:男性组63名,女性组38名,两组年龄比较差异无统计学意义(Z=-1.946,P=0.052,>0.05),具有可比性。根据单向有序资料非参数检验,男性矮小症儿童在维生素D营养等级分布与女性矮小症儿童比较,差别无统计学意义(Z=-0.094,P=0.925,>0.05),且男女患儿在血清维生素D水平上比较亦无统计学差异(Z=-0.547,P=0.585,>0.05),提示在本研究中,男女矮小症儿童在维生素D水平和等级分布上不存在差别。2、按年龄分组:学龄前期组29名、非学龄前期组72名,根据卡方检验,两组患儿的性别构成比比较差异无统计学意义(P=0.343,>0.05),具有可比性。两组儿童的维生素D水平比较差异有统计学意义(Z=-2.988,P=0.003,<0.05),学龄前期组血清维生素D水平(18.0(12.3～23.5mg/ml)较非学龄前期组(12.4(9.5～17.8)mg/ml)高;不同年龄分期矮小症儿童的维生素D营养等级分布比较差异亦有统计学意义(Z=-2.671,P=0.008,<0.05),学龄前期组矮小症儿童维生素D缺乏率(24.1%)小于非学龄期(48.6%),充足率(34.5%)大于非学龄期(13.9%),总体来看,学龄前期矮小症儿童维生素D营养状态明显优于非学龄前期;3、按病因分组:生长激素缺乏症(GHD)组共46名,特发性矮小症(ISS)组共55名,两组在性别构成及年龄方面比较差异均无统计学意义(χ~2=0.488,P=0.485,Z=-1.946,P=0.052,>0.05),具有可比性。根据非参数检验,不同类型矮小症患儿的维生素D营养状态等级分布比较差异有统计学意义(Z=-2.933,p=0.003,<0.05),GHD组患儿维生素D缺乏率(56.5%)较ISS组(29.1%)高,且两组患儿血清维生素D水平比较亦有统计学差异(Z=-2.653,P=0.008,<0.01),GHD组的维生素D水平(10.8(9.5～17.1)mg/ml)明显低于ISS组(16.7(10.8～20.8)mg/ml),总体来说,GHD组的维生素D营养状况较ISS组差。4、单因素二元Logistic回归分析:以GHD的诊断标准(GH激发峰值<10μg/L),将发生GHD赋值为1,不发生GHD(即ISS)赋值为0,并以GHD作为因变量,将各项生长参数及临床指标包括性别、年龄、身高、体重、BMI、骨龄、BAD、维生素D水平分别作为自变量,进行单因素二元Logistic回归分析,结果显示维生素D水平与GHD的发生显著关联(P=0.015,<0.05),且维生素D水平是GHD的保护因素(β=-0.084,<0;OR=0.920,<1)。5、ROC曲线评价维生素D水平对GHD的预判能力:将单因素二元Logistic回归分析得出的独立影响因素---血清维生素D水平作为检验变量作ROC曲线分析,结果显示维生素D水平预测模型的曲线下面积为0.700,P=0.008,<0.05;当血清维生素D含量小于15.665ng/ml时,敏感度为0.739,特异度为0.6,对GHD的发生有一定预判作用。结论:1、本研究中101例矮小症患儿血清维生素D平均含量为15.0±6.7ng/ml,其中80.2%的患儿血清维生素D水平处于不足和缺乏阶段,因而临床医生及家长应注意矮小症儿童血清维生素D的监测与补充。2、本研究中矮小症患儿血清维生素D营养状况与性别无关。3、本研究中矮小症患儿随着年龄增长,维生素D不足与缺乏率也随之增高。4、本研究中GHD组维生素D营养状况较ISS组差,二分类Logistic回归显示维生素D水平是GHD保护因素,ROC曲线分析维生素D在小于15.665ng/ml时对GHD的诊断有一定的价值。更多还原

【Abstract】 Objective: To investigate the nutritional status and distribution of vitamin D in serum of children with different gender,different age groups and different types of short stature in the Department of Pediatrics of Yan’an University Affiliated Hospital for the first time,and to study the value of vitamin D in the diagnosis of growth hormone deficiency.Methods: From january2019 to february2022,101 short stature children who were first diagnosed in pediatrics of Yan’an University Affiliated Hospital and met the Naxi criteria were selected.The groups were as follows: 1.According to gender,they were divided into male group(63 cases)and female group(38 cases);2.They were divided into pre-school age group(29 cases)and non school age group(72 cases);3.They were divided into idiopathic dwarfism group(55 cases)and growth hormone deficiency group(46 cases).The general status and serum 25 hydroxyvitamin D(25-(OH)d)levels in each group were retrospectively investigated,analyzed and compared to further explore the nutritional distribution of vitamin D in children with dwarfism among each group.Single factor binary logistic regression was used to analyze whether growth parameters and clinical indicators(such as serum vitamin D)were independent influencing factors of growth hormone deficiency,Then the independent influencing factors were further analyzed by the receiver operating curve(ROC curve)to evaluate its value in the diagnosis of growth hormone deficiency.Results: According to the inclusion criteria and exclusion criteria,101 children and adolescents with an average age of 8.8±2.7 years were included,ranging from 3 to 14 years old;The average vitamin D level of children with dwarfism was 15.0±6.7ng/ml,which was in the insufficient stage,the lowest was 4.2ng/ml,the highest was 37.85ng/ml;There were 42 vitamin D deficiency patients,accounting for 41.6%,and the content was 9.1±1.9ng/ml;There were 39 patients with deficiency,accounting for 38.6%,and the content was 16.3±2.2ng/ml;There were 19 sufficient patients,accounting for 18.8%,and the content was 25.5±5.1ng/ml;1.Grouped by gender: 63 males and 38 females.There was no significant difference in age between the two groups(Z=-1.946,P=0.052,>0.05),which were comparable.Comparison of vitamin D nutritional status between male and female children with short stature: according to the one-way ordinal data nonparametric test,male children with short stature did not differ from female children in the distribution of vitamin D nutritional status(z =-0.094,P = 0.925,> 0.05),and there was also no difference in serum vitamin D levels between male and female children(z =-0.547,P = 0.585,> 0.05),suggesting that in children with short stature,the,No differences were found in vitamin D levels and distribution between male and female children.2.Grouped by age: 29 in the preschool group and 72 in the non preschool group,there was no significant difference in the gender ratio between the two groups according to the chi square test(P = 0.343,> 0.05)and they were comparable.The difference in vitamin D levels between the two groups was significant(z =-2.988,P = 0.003,< 0.05),with the preschool group having higher serum vitamin D levels(18.0(12.3-23.5mg / ml))than the non preschool group(12.4(9.5-17.8)mg / ml;There were also significant differences in the rank distribution of vitamin D nutritional status among children with short stature at different age stages(z =-2.671,P = 0.008,< 0.05),and the percentage of children with short stature in the preschool age group with vitamin D deficiency(24.1%)was less than that in the non preschool group(48.6%)and with sufficiency(34.5%)was greater than that in the non-school age group(13.9%).Overall,the vitamin D nutritional status of children with short stature in the preschool age group was better than that in the non preschool group;3.Grouped by etiology: 46 in the growth hormone deficiency group and 55 in the idiopathic short stature group,there were no significant differences in gender composition or age between the two groups(χ2= 0.488,P = 0.485,z =-1.946,P =0.052,> 0.05),and they were comparable.According to nonparametric tests,there was a significant difference in the rank distribution of vitamin D nutritional status between children with different types of short stature(z =-2.933,P = 0.003,< 0.05),with a higher percentage of children with vitamin D lack in the GHD group(56.5%)compared with the ISS Group(29.1%)and a significant difference in the serum vitamin D levels between the two groups(z =-2.653,P = 0.008,< 0.01),The vitamin D level of the GHD group(10.8(9.5-17.1)mg/ml)was significantly smaller than that of the ISS Group(16.7(10.8-20.8)mg / ml),and overall,the vitamin D nutritional status of the ISS Group was better than that of the GHD group.4.Univariate binary logistic regression analysis:Taking GH excitation peak <10μg/L as the diagnostic criteria for GHD,the occurrence of GHD was assigned as 1,and the absence of GHD(ie ISS)was assigned as 0.With GHD as the dependent variable,various growth parameters and clinical indicators including gender,age,height,weight,BMI,bone age,BAD,and vitamin D content were used as independent variables,respectively,and a univariate binary logistic regression analysis was performed,the results showed that vitamin D level was significantly associated with GHD(P=0.015,<0.05),and vitamin D level was a protective factor for GHD(β=-0.084,<0;OR=0.920,<1).5.ROC curves assessing the predictive power of vitamin D levels for GHD:The level of vitamin D,an independent influencing factor derived from binary logistic regression analysis,was used as the testing variable for ROC curve analysis,the results showed that the area under the curve of the predictive model for vitamin D levels was 0.700,P = 0.008,< 0.05;When the serum vitamin D level was less than 15.665mg/ml,the sensitivity was 0.739,the specificity was 0.6,and it was a good predictor of GHD.Conclusions:1.In this study,the average content of serum vitamin D in 101 children with dwarfism was 15.0±6.7ng/ml,of which 80.2% were in the stage of deficiency and deficiency.Therefore,clinicians and parents should pay attention to the monitoring and supplementation of serum vitamin D in children with dwarfism.2.In this study,the serum vitamin D nutritional status of children with dwarfism was not related to gender.3.In this study,the vitamin D deficiency and deficiency rate of children with short stature increased with age.4.In this study,the nutritional status of vitamin D in GHD group was worse than that in ISS Group.Binary logistic regression showed that vitamin D level was the protective factor of GHD.ROC curve analysis of vitamin D was of certain value in the diagnosis of GHD when it was less than 15.665ng/ml.更多还原