儿童特发性性早熟环境危险因素及其身心发育分离研究
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摘要
目的探讨早期生长发育和成长环境、玉米赤霉烯酮(ZEA)及二氯二苯二氯乙烯(p,p'-DDE)两种环境内分泌干扰物与特发性性早熟(IPP)的关系;分析IPP儿童生理发育与心理发育的相关性。
方法采用病例对照研究方法,病例组为临床确诊的IPP儿童,共78例;对照组为与病例组年龄、性别成组匹配的正常体检儿童,共100例。对所有研究对象的宫内生长和出生后生长速率、母孕期疾病及心理应激、母亲和同辈亲属早发育史、家庭经济条件、童年期带养及饮食习惯等进行问卷调查,并留取血标本。采用logistic回归模型筛选IPP儿童早期生长发育和成长环境中的危险因素;采用酶标免疫分析定量法测定血清ZEA浓度和气相色谱内标法测定p,p′-DDE的浓度,比较两组间差异的统计学意义以分析其与IPP的相关性。再分析早期生长发育与成长环境和两种环境内分泌干扰物联合作用对IPP的影响,分别分析二者间的统计学交互作用和生物学交互作用;统计学交互作用通过构造乘积项早期生长发育与成长环境×环境内分泌干扰物,在logistic回归模型中分析乘积项的参数估计值;生物学交互作用通过构造新变量建立logistic回归模型及Excel计算表,分析三个评价指标:相对超危险度比(RERI)、归因比(AP)和交互作用指数(S)。
对所有研究对象进行身高、体重、腰围、骨龄、磁共振波谱等生理发育指标的检查;同时运用儿童抑郁量表和Conners儿童行为量表评定心理健康状况,运用韦氏儿童智力量表和STROOP试验评定认知功能发育。分析IPP儿童生理及心理发育成熟度与对照组儿童的差异。以早期生长发育和成长环境中的危险因素作为控制变量,在控制这些危险因素后,分析这种差异是否持续存在。
结果病例组中的早产、小于胎龄儿(SGA)、母孕期疾病、母孕期心理创伤、家庭经济状况佳、非城市居住地、收养儿、母亲月经初潮早(≤12岁)、同辈亲属早发育、婴幼儿期父亲陪伴少、学龄前期父亲陪伴少、学龄期父亲陪伴少的比率均显著高于对照组(P<0.05);多因素非条件logistic回归分析显示,SGA、母孕期疾病、母亲月经初潮早、同辈亲属早发育、学龄前期父亲陪伴少为IPP的危险因素。病例组ZEA的浓度及阳性检出率显著高于对照组(P<0.01);而两组儿童血清p,p′-DDE的浓度差异无显著性,病例组p,p′-DDE阳性检出率显著高于对照组(P<0.05)。对早期生长发育与成长环境和ZEA联合作用分析显示,二者之间无统计学交互作用,logistic回归模型中早期生长发育与成长环境×ZEA的P值为0.791。但存在生物学交互作用,RERI=34.562,AP =0.745,S =4.193。
IPP儿童骨龄显著高于对照组儿童(P=0.000),而身高、体重、腰围、BMI及磁共振波谱等与对照组差异无显著性。IPP儿童心身障碍及总的行为问题检出率显著高于对照组(P<0.05),加工速度智商显著低于对照组。校正骨龄后,IPP儿童言语理解、知觉推理、工作记忆、加工速度分量表智商及总智商均显著低于对照组(P<0.05)。在控制了早期生长发育与成长环境中的的危险因素后,IPP儿童骨龄仍高于对照组儿童,加工速度智商及校正骨龄后各项智商水平仍低于对照组儿童(P<0.05)。
结论儿童早期生长发育与成长环境和玉米赤霉烯酮的相加作用与IPP关联强度增加。IPP儿童存在生理发育提前及心理发育滞后,也即存在身心发育分离现象;且在校正了早期生长发育与成长环境的各危险因素后,这种分离现象持续存在。
Objective To evaluate the effects of early physical developments and growth environments, ZEA and p,p'-DDE on IPP patients, and the association between physical developments and mental developments in IPP patients.
Methods A case-control study was conducted among 78 IPP patients and 100 controlled children with age, sex mated. Growth speed of prenatal and after birth, disease and psychopathological symptoms during pregnancy, early puberty of mother and same-degree relatives, family economic condition, accompany of parents in childhood and diet habits were assessed through questionnaires. Multivariate logistic regression was used to estimated early g physical developments and growth environments on odds of IPP; risk factors of IPP were selected. Serum ZEA and p,p′-DDE were tested with ELISA and gas chromatography respectively and the results were analyzed between two groups. The effects of combination of risk factors of early physical developments and growth environments and EDCs on IPP were also analyzed. Statistical interaction and biological interaction were analyzed respectively. A product variable, early physical developments and growth environments×EDCs, was set in logistic regression model. Statistical interaction was evaluated by odds ratio of product variable. A new viariable setted in logistic regression modle and Excel sheet were used to calculatethe measures of biological interaction. Three measures of biological interaction were presented: RERI, the relative excess risk due to interaction; AP, the attributable proportion due to interaction; and S, the synergy index. Physical developments, including height, weight, waistline, bone age and 1H-MRS, were evaluated. Mental developments were also tested by using Children’s Depression Inventory, Conners parent rating scale, WISC-Ⅳand STROOP test. Variations of physical and mental developments between IPP patients and the control were analyzed. Risk factors of early physical developments and growth environments were selected and regarded as control variables. After controlling the relative risk factors, those variations were reanalyzed.
Results Relative to the control, the rates of preterm birth, SGA, disease and psychopathological symptoms during pregnancy, better family economic condition, lived in rural, adoption, early maternal menarche (≤12y), early puberty of same-degree relatives, father absence during all childhood were significantly high in IPP patients (P<0.05). In the multivariate logistic regression models, SGA, disease during pregnancy, early maternal menarche, early puberty of same-degree relatives and father absence in 4-6 years old persisted as risk factors of IPP. Concentration of ZEA and positive rates in IPP group were significantly higher than the control. There was no difference of the concentration of p,p′-DDE between two groups, while the positive rate of p,p′-DDE in IPP group was significantly higher than the control (P<0.05). There was no statistical interaction between two risk factors of early physical developments and growth environments and ZEA. P value of product variable was 0.791. There was biological interaction between two risk factors (RERI=34.562,AP =0.745,S =4.193).
The bone age of IPP patients were significantly higher than that of the control (P=0.000), there were no difference between two groups in other physical developments, such as height, weight, waistline, BMI and 1H-MRS. In the tests of mental health, psychosomatic disorder and positive rate of total behavior problems in IPP group were significantly higher than the control (P<0.05). Processing Speed intelligence quotient (IQ) in IPP group were significantly lower than the control (P<0.05). After adjusting for bone age, Verbal Comprehension, Perceptual Reasoning, Working Memory, Processing Speed, and total IQ in IPP group were all significantly lower than the control (P<0.05). After adjusting for risk factors of early physical developments and growth environments, the bone age of IPP patients were still higher than the control, and Processing Speed IQ and all IQ items after adjusting for bone age were also lower than the control (P<0.05).
Conclusions The effects of early physical developments and growth environments and ZEA on IPP have synergism. Physical developments are advanced, and cognitive functions are lagggard in IPP patients. That is there is mismatch between physical development and cognitive function. Even after adjusting for risk factors of early physical developments and growth environments, this mismatch is still existed.
方法采用病例对照研究方法,病例组为临床确诊的IPP儿童,共78例;对照组为与病例组年龄、性别成组匹配的正常体检儿童,共100例。对所有研究对象的宫内生长和出生后生长速率、母孕期疾病及心理应激、母亲和同辈亲属早发育史、家庭经济条件、童年期带养及饮食习惯等进行问卷调查,并留取血标本。采用logistic回归模型筛选IPP儿童早期生长发育和成长环境中的危险因素;采用酶标免疫分析定量法测定血清ZEA浓度和气相色谱内标法测定p,p′-DDE的浓度,比较两组间差异的统计学意义以分析其与IPP的相关性。再分析早期生长发育与成长环境和两种环境内分泌干扰物联合作用对IPP的影响,分别分析二者间的统计学交互作用和生物学交互作用;统计学交互作用通过构造乘积项早期生长发育与成长环境×环境内分泌干扰物,在logistic回归模型中分析乘积项的参数估计值;生物学交互作用通过构造新变量建立logistic回归模型及Excel计算表,分析三个评价指标:相对超危险度比(RERI)、归因比(AP)和交互作用指数(S)。
对所有研究对象进行身高、体重、腰围、骨龄、磁共振波谱等生理发育指标的检查;同时运用儿童抑郁量表和Conners儿童行为量表评定心理健康状况,运用韦氏儿童智力量表和STROOP试验评定认知功能发育。分析IPP儿童生理及心理发育成熟度与对照组儿童的差异。以早期生长发育和成长环境中的危险因素作为控制变量,在控制这些危险因素后,分析这种差异是否持续存在。
结果病例组中的早产、小于胎龄儿(SGA)、母孕期疾病、母孕期心理创伤、家庭经济状况佳、非城市居住地、收养儿、母亲月经初潮早(≤12岁)、同辈亲属早发育、婴幼儿期父亲陪伴少、学龄前期父亲陪伴少、学龄期父亲陪伴少的比率均显著高于对照组(P<0.05);多因素非条件logistic回归分析显示,SGA、母孕期疾病、母亲月经初潮早、同辈亲属早发育、学龄前期父亲陪伴少为IPP的危险因素。病例组ZEA的浓度及阳性检出率显著高于对照组(P<0.01);而两组儿童血清p,p′-DDE的浓度差异无显著性,病例组p,p′-DDE阳性检出率显著高于对照组(P<0.05)。对早期生长发育与成长环境和ZEA联合作用分析显示,二者之间无统计学交互作用,logistic回归模型中早期生长发育与成长环境×ZEA的P值为0.791。但存在生物学交互作用,RERI=34.562,AP =0.745,S =4.193。
IPP儿童骨龄显著高于对照组儿童(P=0.000),而身高、体重、腰围、BMI及磁共振波谱等与对照组差异无显著性。IPP儿童心身障碍及总的行为问题检出率显著高于对照组(P<0.05),加工速度智商显著低于对照组。校正骨龄后,IPP儿童言语理解、知觉推理、工作记忆、加工速度分量表智商及总智商均显著低于对照组(P<0.05)。在控制了早期生长发育与成长环境中的的危险因素后,IPP儿童骨龄仍高于对照组儿童,加工速度智商及校正骨龄后各项智商水平仍低于对照组儿童(P<0.05)。
结论儿童早期生长发育与成长环境和玉米赤霉烯酮的相加作用与IPP关联强度增加。IPP儿童存在生理发育提前及心理发育滞后,也即存在身心发育分离现象;且在校正了早期生长发育与成长环境的各危险因素后,这种分离现象持续存在。
Objective To evaluate the effects of early physical developments and growth environments, ZEA and p,p'-DDE on IPP patients, and the association between physical developments and mental developments in IPP patients.
Methods A case-control study was conducted among 78 IPP patients and 100 controlled children with age, sex mated. Growth speed of prenatal and after birth, disease and psychopathological symptoms during pregnancy, early puberty of mother and same-degree relatives, family economic condition, accompany of parents in childhood and diet habits were assessed through questionnaires. Multivariate logistic regression was used to estimated early g physical developments and growth environments on odds of IPP; risk factors of IPP were selected. Serum ZEA and p,p′-DDE were tested with ELISA and gas chromatography respectively and the results were analyzed between two groups. The effects of combination of risk factors of early physical developments and growth environments and EDCs on IPP were also analyzed. Statistical interaction and biological interaction were analyzed respectively. A product variable, early physical developments and growth environments×EDCs, was set in logistic regression model. Statistical interaction was evaluated by odds ratio of product variable. A new viariable setted in logistic regression modle and Excel sheet were used to calculatethe measures of biological interaction. Three measures of biological interaction were presented: RERI, the relative excess risk due to interaction; AP, the attributable proportion due to interaction; and S, the synergy index. Physical developments, including height, weight, waistline, bone age and 1H-MRS, were evaluated. Mental developments were also tested by using Children’s Depression Inventory, Conners parent rating scale, WISC-Ⅳand STROOP test. Variations of physical and mental developments between IPP patients and the control were analyzed. Risk factors of early physical developments and growth environments were selected and regarded as control variables. After controlling the relative risk factors, those variations were reanalyzed.
Results Relative to the control, the rates of preterm birth, SGA, disease and psychopathological symptoms during pregnancy, better family economic condition, lived in rural, adoption, early maternal menarche (≤12y), early puberty of same-degree relatives, father absence during all childhood were significantly high in IPP patients (P<0.05). In the multivariate logistic regression models, SGA, disease during pregnancy, early maternal menarche, early puberty of same-degree relatives and father absence in 4-6 years old persisted as risk factors of IPP. Concentration of ZEA and positive rates in IPP group were significantly higher than the control. There was no difference of the concentration of p,p′-DDE between two groups, while the positive rate of p,p′-DDE in IPP group was significantly higher than the control (P<0.05). There was no statistical interaction between two risk factors of early physical developments and growth environments and ZEA. P value of product variable was 0.791. There was biological interaction between two risk factors (RERI=34.562,AP =0.745,S =4.193).
The bone age of IPP patients were significantly higher than that of the control (P=0.000), there were no difference between two groups in other physical developments, such as height, weight, waistline, BMI and 1H-MRS. In the tests of mental health, psychosomatic disorder and positive rate of total behavior problems in IPP group were significantly higher than the control (P<0.05). Processing Speed intelligence quotient (IQ) in IPP group were significantly lower than the control (P<0.05). After adjusting for bone age, Verbal Comprehension, Perceptual Reasoning, Working Memory, Processing Speed, and total IQ in IPP group were all significantly lower than the control (P<0.05). After adjusting for risk factors of early physical developments and growth environments, the bone age of IPP patients were still higher than the control, and Processing Speed IQ and all IQ items after adjusting for bone age were also lower than the control (P<0.05).
Conclusions The effects of early physical developments and growth environments and ZEA on IPP have synergism. Physical developments are advanced, and cognitive functions are lagggard in IPP patients. That is there is mismatch between physical development and cognitive function. Even after adjusting for risk factors of early physical developments and growth environments, this mismatch is still existed.
引文
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