不同标准诊断的亚临床甲状腺功能减退症及甲状腺过氧化物酶抗体阳性对妊娠的影响

Comparison of the effect of different diagnostic criteria of subclinical hypothyroidism and positive TPO-Ab on pregnancy outcomes

目的 探讨不同促甲状腺激素（TSH）标准诊断的妊娠早期亚临床甲状腺功能减退症（亚甲减）及甲状腺过氧化物酶抗体（TPO-Ab）阳性对妊娠的影响.方法 采用前瞻性研究的方法,收集2011年8月至2013年2月在陕西省妇幼保健院产科首次产检并分娩的孕妇3 244例.按美国甲状腺协会标准,以血清TSH水平＞2.50 mU/L、血清游离甲状腺素（FT4）水平正常的妊娠合并亚甲减孕妇为国外标准组;按照2012年国内制定的《妊娠和产后甲状腺疾病诊治指南》标准,以血清TSH水平＞5.76 mU/L、血清FT4水平正常的妊娠合并亚甲减孕妇为国内标准组;TSH水平介于2.50～5.76 mU/L之间的妊娠合并亚甲减孕妇为研究观察组;选择TSH水平＜2.50 mU/L,且TPO-Ab检查结果阴性的健康孕妇作为对照组.对各组孕妇的TPO-Ab阳性检查结果及其与妊娠结局及并发症进行分析.结果 （1）国外标准组亚甲减孕妇共635例,发生率为19.57％（635/3 244）.国内标准组亚甲减孕妇共70例,发生率为2.16％（70/3 244）.两组亚甲减发生率比较,差异有统计学意义（P＜0.01）.研究观察组亚甲减孕妇共565例,发生率为17.42％（565/3 244）,与国内标准组的亚甲减发生率比较,差异有统计学意义（P＜0.01）;与国外标准组的亚甲减发生率比较,差异无统计学意义（P＞0.05）.（2）3 244例孕妇中TPO-Ab阳性402例,阴性2 842例.其中,国外标准组阳性318例,阳性孕妇的亚甲减发生率为79.10％（318/402）;阴性317例,阴性孕妇的亚甲减发生率为11.15％（317/2 842）,两者发生率比较,差异有统计学意义（P＜0.01）.国内标准组阳性孕妇46例,阳性孕妇的亚甲减发生率为11.44％（46/402）;阴性24例,阴性孕妇的亚甲减发生率为0.84％ （24/2 842）,两者发生率比较,差异有统计学意义（P＜0.01）.研究观察组阳性孕妇272例,阳性孕妇的亚甲减发生率为67.66％（272/402）;阴性293例,阴性孕妇的亚甲减发生率为10.31％（293/2 842）,两者发生率比较,差异有统计学意义（P＜0.01）.（3）国外标准组孕妇流产、早产、妊娠期高血压疾病、妊娠期糖尿病（GDM）等的发生率分别与对照组比较,差异均有统计学意义（P＜0.05）;胎盘早剥、胎儿窘迫发生率比较,差异均无统计学意义（P＞0.05）.国内标准组孕妇流产、早产、妊娠期高血压疾病、GDM等的发生率分别与对照组比较,差异均有统计学意义（P＜0.05）;胎盘早剥、胎儿窘迫发生率比较,差异均无统计学意义（P＞0.05）.研究观察组孕妇流产、妊娠期高血压疾病、GDM等的发生率分别与对照组比较,差异均有统计学意义（P＜0.05）;早产、胎盘早剥及胎儿窘迫的发生率比较,差异均无统计学意义（P＞0.05）.（4）国外标准组TPO-Ab阳性孕妇流产、早产、胎盘早剥、妊娠合并贫血、胎儿窘迫的发生率分别与TPO-Ab阴性孕妇比较,差异均无统计学意义（P＞0.05）;但两者的妊娠期高血压疾病、GDM的发生率比较,差异均有统计学意义（P＜0.05）.国内标准组TPO-Ab阳性孕妇流产、早产、妊娠期高血压疾病、GDM、胎盘早剥、胎儿窘迫的发生率与TPO-Ab阴性孕妇比较,呈增高趋势,但分别比较,差异均无统计学意义（P＞0.05）.研究观察组TPO-Ab阳性孕妇妊娠期高血压疾病、GDM的发生率与TPO-Ab阴性孕妇比较,差异均有统计学意义（P＜0.05）;而流产、早产、胎盘早剥、胎儿窘迫的发生率比较,差异均无统计学意义（P＞0.05）.结论 （1）妊娠早期亚甲减孕妇患病率较高,且可导致不良妊娠结局增加;（2）TPO-Ab阳性对预测甲状腺功能异常和GDM发病风险具有重要的临床意义;（3）相对比较,按我国2012年标准（血清TSH水平＞5.76mU/L）诊断亚甲减可能过于谨慎,不利于孕期管理;按美国标准（血清TSH水平＞2.5 mU/L）诊断亚甲减对孕期管理更加安全,以获得更良好的妊娠结局.

Objective To explore the effect of different diagnositic criteria of subclinical hypothyroidism using thyroid stimulating hormone （TSH） and positive thyroid peroxidase antibodies （TPO-Ab） on the pregnancy outcomes. Methods 3 244 pregnant women who had their antenatal care and delivered in Child and Maternity Health Hospital of Shannxi Province August from 2011 to February 2013 were recruited prospectively. According to the standard of American Thyroid Association （ATA）, pregnant women with normal serum free thyroxine （FT4） whose serum TSH level〉 2.50 mU/L were diagnosed as subclinical hypothyroidism in pregnancy （foreign standard group）. According to the Guideline of Diagnosis and Therapy of Prenatal and Postpartum Thyroid Disease made by Chinese Society of Endocrinology and Chinese Society of Perinatal Medicine in 2012, pregnant women with serum TSH level〉 5.76 mU/L, and normal FT4 were diagnosed as subclinical hypothyroidism in pregnancy（national standard group）. Pregnant women with subclinical hypothyroidism whose serum TSH levels were between 2.50-5.76 mU/L were referred as the study observed group; and pregnant women with serum TSH level〈 2.50 mU/L and negative TPO-Ab were referred as the control group. Positive TPO-Ab results and the pregnancy outcomes were analyzed. Results （1） There were 635 cases in the foreign standard group, with the incidence of 19.57% （635/3 244）. And there were 70 cases in the national standard group, with the incidence of 2.16% （70/3 244）. There were statistically significant difference between the two groups （P〈0.01）. There were 565 cases in the study observed group, with the incidence of 17.42% （565/3 244）. There was statistically significant difference（P〈 0.01） when compared with the national standard group; while there was no statistically significant difference （P〉0.05） when compared with the foreign standard group. （2） Among the 3 244 cases, 402 cases had positive TPO-Ab. 318 positive cases were in the foreign standard group, and the incidence of subclinical hypothyroidism was 79.10% （318/402）. There were 317 negative cases in the foreign standard group, with the incidence of 11.15% （317/2 842）. The difference was statistically significant （P〈0.01） between them. In the national standard group, 46 cases had positive TPO-Ab, with the incidence of 11.44% （46/402）, and 24 cases had negative result, with the incidence of 0.84% （24/2 842）. There were statistically significant difference （P〈0.01） between them. In the study observed group, 272 cases were TPO-Ab positive, with the incidence of 67.66% （272/402）, and 293 cases were negative, with the incidence of 10.31% （293/2 842）, the difference was statistically significant （P〈0.01）. （3） The incidence of miscarriage, premature delivery, gestational hypertension disease, gestational diabetes mellitus （GDM） in the foreign standard group had statistically significant differences （P〈0.05） when compared with the control group, respectively. While there was no statistically significant difference （P〉0.05） in the incidence of placental abruption or fetal distress. And the incidence of miscarriage, premature delivery, gestational hypertension disease, GDM in the national standard group had statistical significant difference （P〈0.05） compared with the control group, respectively. While there was no statistically significant difference （P〉0.05） in the incidence of placental abruption or fetal distress. This study observed group of pregnant women＇ s abortion, gestational hypertension disease, GDM incidence respectively compared with control group, the difference had statistical significance （P〈 0.05）; but in preterm labor, placental abruption, and fetal distress incidence, there were no statistically significant difference （P〉0.05）. （4） The incidence of miscarriage, premature delivery, gestational hypertension disease, GDM, placental ahruption, fetal distress in the TPO-Ab positive cases of the national standard group showed an increase trend when compared with TPO-Ab negative cases, with no statistically significant difference （P〉0.05）. The incidence of gestational hypertension disease and GDM in the TPO-Ab positive cases of the study observed group had statistical significance difference （P〈0.05） when compared with TPO-Ab negative cases; while the incidence of miscarriage, premature birth, placental abruption, fetal distress had no statistically significant difference （P〉0.05）. The incidence of gestational hypertension disease and GDM in the TPO-Ab positive cases had statistically significance difference when compared with TPO-Ab negtive cases of foreign standard group （P〈0.05）. Conclusions （1） The incidence of subclinical hypothyroidism is rather high during early pregnancy and can lead to adverse pregnancy outcome. （2） Positive TPO-Ab result has important predictive value of the thyroid dysfunction and GDM. （3） Relatively, the ATA standard of diagnosis （serum TSH level〉 2.50 mU/L） is safer for the antenatal care; the national standard （serum TSH level〉 5.76 mU/L） is not conducive to pregnancy management.