新生儿外周血促甲状腺激素升高与母亲甲状腺功能关系的研究

Relationship of Neonatal High Blood Thyroid-Stimulating Hormone and Their Mother′s Thyroid Function

目的探索新生儿外周血促甲状腺激素(thyroid-stimulating hormone,TSH)升高与母体甲状腺功能的关系。方法自2000年5月至2009年8月,潍坊市新生儿疾病筛查中心对在潍坊市妇幼保健院出生的615767例新生儿进行先天性甲状腺功能低下(congenital hypothyridism,CH)筛查。将筛查后确诊为CH呈阳性的195例(0.32‰,195/615767)患儿中,符合本研究要求的159对患儿及其母亲,纳入CH呈阳性患儿(母亲)组(A组);选择本次筛查认为可疑CH患儿(TSH≥15μIU/mL)及其母亲986对(不包括CH呈阳性患儿),纳入可疑CH患儿(母亲)组(B组)。同时。随机抽检2008年3月至2009年8月在潍坊市新生儿疾病筛查中心接受筛查的新生儿中,外周血TSH值正常儿及其母亲225对,纳入对照组(本研究遵循的程序符合潍坊市妇幼保健院人体试验委员会制定的伦理学标准,得到该委员会批准,分组征得受试对象监护人的知情同意,并与其签署临床研究知情同意书)。各组新生儿母亲,排除甲状腺功能异常外其他可能导致甲状腺功能异常疾病。采用新生儿干血片检测外周血TSH值法,进行CH筛查,筛选出TSH≥15μIU/mL新生儿后,采集其母肘静脉血2mL,利用电化学发光免疫检测分析系统,测定母血清中TSH、总三碘甲腺原氨酸(total triiodo thyronine,TT3)、总甲状腺素(total thyroxine,TT4)、游离三碘甲腺原氨酸(free triiodo thyronine,FT3)、游离甲状腺素(free thyroxine,FT4)、甲状腺过氧化物酶抗体(thyroid peroxidase antibody,TPO-Ab)、甲状腺球蛋白(thyroglobulin,TG)、抗甲状腺球蛋白抗体(thyroglobulin antibody,TG-Ab)等参数,并分析其甲状腺功能状态,判断母亲甲状腺功能状态变化与新生儿血TSH升高的关系。结果①A组母亲甲状腺功能异常率为23.3%(37/159),B组母亲异常率为7.00%(69/986),对照组母亲异常率为1.78%(4/225)。经χ2检验,三组母亲甲状腺功能异常率比较,差异有显著意义(P<0.01)。②A,B组母亲与对照组母亲TSH,TPO-Ab,TG和TG-Ab四项参数比较,差异有显著意义(P<0.01)。③新生儿外周血TSH升高与其母亲血清TSH,TPO-Ab,TG和TG-Ab的异常相关(P<0.01)。④应用分类变量关联分析的统计学方法进行处理显示,新生儿CH发病率与母亲血清TSH(r=0.205)、FT3(r=0.127)、FT4(r=0.206)、TPO-Ab(r=0.292)、TG(r=0.214)、TG-Ab(r=0.236)异常呈正相关;与母亲TT3(r=0.015)、TT4(r=0.065)无相关性。结论①新生儿外周血TSH升高与母亲甲状腺功能异常有关。②母亲TSH,TPO-Ab,TG和TG-Ab异常,与新生儿外周血TSH升高有关。③母亲甲状腺功能异常,可能导致新生儿CH发病。

Objective To explore the relationship between neonatal blood thyroid-stimulating hormone （TSH） and maternal thyroid function.Methods From May 2000 to August 2009,615 767 newborns in Weifang City have been screened congenital hypothyroidism （CH） by detecting TSH value of dried blood spots in the Newborn Screening Centre of Weifang City.A total of 195 cases （0.32 ‰,195/615 767） were diagnosed as CH.Among them,159 pairs of CH-positive children and their mothers were included in to group A,other 986 pairs of suspected CH children （TSH≥ 15 μIU/mL） and their mothers （not including the CH-positive children） were included into group B.At the same time,225 pairs of normal children and their mothers who received screening were recruited into control group.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Maternal and Child Health Hospital of Weifang City.Informed consent was obtained from all participants.Mothers in each group excluded patients with abnormal thyroid function and other diseases that may cause thyroid dysfunction.Detected newborn dried blood TSH value to screening for CH.Collected mother′s venous blood （2 mL） when the newborn′s TSH≥15 μIU/mL,then analyzed the relationship between mother′s thyroid function change trend and their newborn′s elevated serum TSH by electrochemiluminescence immunoassay system,including maternal serum TSH,total triiodo thyronine（TT3）,total thyroxine （TT4）,free triiodo thyronine（FT3）,free thyroxine （FT4）,thyroid peroxidase antibody（TPO-Ab）,thyroglobulin （TG）,thyroglobulin antibody（TG-Ab）.Results ①The thyroid dysfunction of mother in group A was 23.3% （37/159）,group B was 7.00% （69/986）,and control group was 1.78% （4/225）.The difference was significant among three groups by chi-square test （P〈0.01）.② There was significant difference of TSH,TPO-Ab,TG and TG-Ab of mother′s in group A,B and control group （P〈0.01）.③ The incensement of neonatal blood TSH was related to the exception of their mother′s TSH,TPO-Ab,TG and TG-Ab （P〈0.01）.④Statistical analysis showed that the incidence of CH was positively correlated with the abnormal of mother′s TSH （r=0.205）,FT3 （r=0.127）,FT4 （r=0.206）,TPO-Ab （r=0.292）,TG （r=0.214）,TG-Ab （r=0.236） and was no correlated with mother′s TT3 （r=0.015）,TT4 （r=0.065）.Conclusion ①The incensement of neonatal blood TSH was related to their mother′s thyroid dysfunction.②The newborn elevated TSH was positively correlated with the abnormal of mother′s TSH,TPO-Ab,TG and TG-Ab.③Mother thyroid dysfunction could lead to neonatal CH.