不同诊断标准下妊娠期亚临床甲状腺功能减退与不良妊娠结局的相关性研究
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摘要
目的比较不同诊断标准下妊娠期亚临床甲状腺功能减退(SCH)的患病率,探讨不同诊断标准下妊娠期SCH与不良妊娠结局的相关性。方法选择2016年3月至2017年10月在首都医科大学附属北京友谊医院妇产科门诊首次就诊并建立围产保健档案的妊娠妇女共5 554例进行前瞻性队列研究。于妊娠第8～10周行甲状腺过氧化物酶抗体(TPOAb)和甲状腺功能(TSH、FT4)的测定;于妊娠第24～26周、妊娠第36～37周行甲状腺功能(TSH、FT4)的测定。并随访至分娩,收集妊娠期糖尿病、妊娠期高血压疾病、胎盘早剥、前置胎盘、早产、产后出血、巨大胎儿、低出生体重儿等不良妊娠结局资料。比较不同诊断标准下SCH的发生率及妊娠期SCH与不良妊娠结局的相关性。结果按照本单位标准、2011年美国甲状腺学会(ATA)标准和2017年ATA标准分别研究SCH的患病率如下:妊娠期SCH患病率分别为8. 96%(498/5 554)、26. 53%(1 474/5 554)、7. 67%(426/5 554);按照本单位标准和2017年ATA标准诊断的SCH伴TPOAb阳性组的低出生体重儿的发生率显著高于甲状腺功能正常组(8. 77%vs. 6. 22%; 9. 52%vs. 6. 32%,P<0. 05);按照本单位标准和2017年ATA标准诊断的SCH伴TPOAb阳性组的巨大胎儿的发生率显著高于甲状腺功能正常组(8. 77%vs. 6. 80%; 9. 95%vs. 7. 03%,P <0. 05);按照2011年ATA标准诊断的SCH TPOAb阳性组、SCH TPOAb阴性组与甲状腺功能正常组比较,妊娠结局差异均无统计学意义(P> 0. 05)。结论建议本单位妊娠期特异性参考值或以TSH> 4. 0 m IU/L作为的参考值上限诊断妊娠期SCH;大多数妊娠期SCH发生于孕早期和孕中期;妊娠期SCH与巨大胎儿及低出生体重儿的发生存在相关性。
Objective To calculate and compare the prevalence of subclinical hypothyroidism with different diagnostic criteria and to analyze the correlation between subclinical hypothyroidism and adverse pregnancy outcomes. Methods This prospective cohort study included 5 554 women from the department of obstetrics and gynecology,Beijing Friendship Hospital,Capital Medical University during March 2016 to October2017. Thyrotropin( TSH),free thyroxine( FT4),and thyroid peroxidase antibody( TPOAb) were measured in 8-10 gestational weeks. Thyroid function( TSH,FT4) were examined in 24-26 and 36-37 gestational weeks. The outcome measured in follow up period was the incidence of pregnancy-induced hypertension,gestational diabetes mellitus,caesarean section,placental abruption,placenta previa,low birth weight,preterm,macrosomia. The risk of adverse pregnancy outcomes were compared with different diagnostic criteria in subclinical hypothyroidism women.The prevalence of subclinical hypothyroidism with different diagnostic criteria were calculated and correlation between subclinical hypothyroidism and pregnancy outcome during pregnancy was analyzed. Results According to the upper limit of trimester-specific TSH reference range by the hospital,specific reference range of thyroid function during pregnancy by 2011 ATA and 2017 ATA guidelines,the incidences of subclinical hypothyroidism,were 8. 96%( 498/5 554),26. 53%( 1 474/5 554) and 8. 96%( 498/5 554),respectively. There was significantly higher incidence in low birth weight among TPOAb-positive subclinical hypothyroidism( SCH) group diagnosed by the upper limit of trimester-specific TSH reference range upper by the hospital and specific reference range of thyroid function during pregnancy by the 2017 ATA guideline recommending compared to euthyroid women( 8. 77% vs. 6. 22%; 9. 52% vs. 6. 32%,P < 0. 05). There were significantly higher incidence at macrosomia among TPOAb-positive SCH group diagnosed by the upper limit of trimester-specific TSH reference range of the hospital and specific reference range of thyroid function during pregnancy by 2017 ATA guideline recommending compared to euthyroid women( 8. 77% vs. 6. 80%; 9. 95%vs. 7. 03%,P < 0. 05). In comparison with euthyroid women,there was no significantly difference in adverse pregnancy outcome in SCH groups diagnosed by specific reference range of thyroid function during pregnancy by 2011 ATA guideline recommending( P > 0. 05). Conclusion It is recommended that the specific reference value of pregnancy in this unit or the reference value of TSH > 4. 0 m IU/L as the upper limit for diagnosis of subclinical hypothyroidism during pregnancy; most of the subclinical hypothyroidism during pregnancy occurs in the first trimester and second trimester; there is a correlation between clinical hypothyroidism and the occurrence of huge fetuses and low birth weight infants.
Objective To calculate and compare the prevalence of subclinical hypothyroidism with different diagnostic criteria and to analyze the correlation between subclinical hypothyroidism and adverse pregnancy outcomes. Methods This prospective cohort study included 5 554 women from the department of obstetrics and gynecology,Beijing Friendship Hospital,Capital Medical University during March 2016 to October2017. Thyrotropin( TSH),free thyroxine( FT4),and thyroid peroxidase antibody( TPOAb) were measured in 8-10 gestational weeks. Thyroid function( TSH,FT4) were examined in 24-26 and 36-37 gestational weeks. The outcome measured in follow up period was the incidence of pregnancy-induced hypertension,gestational diabetes mellitus,caesarean section,placental abruption,placenta previa,low birth weight,preterm,macrosomia. The risk of adverse pregnancy outcomes were compared with different diagnostic criteria in subclinical hypothyroidism women.The prevalence of subclinical hypothyroidism with different diagnostic criteria were calculated and correlation between subclinical hypothyroidism and pregnancy outcome during pregnancy was analyzed. Results According to the upper limit of trimester-specific TSH reference range by the hospital,specific reference range of thyroid function during pregnancy by 2011 ATA and 2017 ATA guidelines,the incidences of subclinical hypothyroidism,were 8. 96%( 498/5 554),26. 53%( 1 474/5 554) and 8. 96%( 498/5 554),respectively. There was significantly higher incidence in low birth weight among TPOAb-positive subclinical hypothyroidism( SCH) group diagnosed by the upper limit of trimester-specific TSH reference range upper by the hospital and specific reference range of thyroid function during pregnancy by the 2017 ATA guideline recommending compared to euthyroid women( 8. 77% vs. 6. 22%; 9. 52% vs. 6. 32%,P < 0. 05). There were significantly higher incidence at macrosomia among TPOAb-positive SCH group diagnosed by the upper limit of trimester-specific TSH reference range of the hospital and specific reference range of thyroid function during pregnancy by 2017 ATA guideline recommending compared to euthyroid women( 8. 77% vs. 6. 80%; 9. 95%vs. 7. 03%,P < 0. 05). In comparison with euthyroid women,there was no significantly difference in adverse pregnancy outcome in SCH groups diagnosed by specific reference range of thyroid function during pregnancy by 2011 ATA guideline recommending( P > 0. 05). Conclusion It is recommended that the specific reference value of pregnancy in this unit or the reference value of TSH > 4. 0 m IU/L as the upper limit for diagnosis of subclinical hypothyroidism during pregnancy; most of the subclinical hypothyroidism during pregnancy occurs in the first trimester and second trimester; there is a correlation between clinical hypothyroidism and the occurrence of huge fetuses and low birth weight infants.
引文
[1]Stagnaro-Green A,Abalovich M,Alexander E,et al.Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum[J].Thyroid,2011,21(10):1081-1125.
[2]中华医学会内分泌学分会,中华医学会围产医学分会.妊娠和产后甲状腺疾病诊治指南[J].中华内分泌代谢杂志,2012,28(5):354-371.
[3]De Groot L,Abalovich M,Alexander EK,et al.Management of thyroid dysfunction during pregnancy and postpartum:an Endocrine Society clinical practice guideline[J].J Clin Endocrinol Metab,2012,97(8):2543-2565.
[4]Brent GA.The debate over thyroid-function screening in pregnancy[J].N Engl J Med,2012,366(6):562-563.
[5]Lazarus J,Brown RS,Daumerie C,et al.2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children[J].Eur Thyroid J,2014,3(2):76-94.
[6]张晓璐.妊娠期甲状腺疾病的临床流行病学调查[D].北京:首都医科大学,2013.
[7]Bliddal S,Boas M,Hilsted L,et al.Thyroid function and autoimmunity in Danish pregnant women after an iodine fortification program and associations with obstetric outcomes[J].Eur J Endocrinol,2015,173(6):709-718.
[8]Rashid M,Rashid MH.Obstetric management of thyroid disease[J].Obstet Gynecol Surv,2007,62(10):680-688.
[9]李元宾,滕卫平,单忠艳,等.妊娠中期妇女亚临床甲状腺异常对后代智力发育影响的研究[J].中华内分泌代谢杂志,2008,24(6):601-604.
[10]Gardosi J.New definition of small for gestational age based on fetal growth potential[J].Horm Res,2006,65 Suppl 3:15-18.
[11]Li CY,Shah ZY,Mao JY,et al.Assessment of thyroid function during first-trimester pregnancy:what is the rational upper limit of serum TSHduring the first trimester in Chinese pregnant women[J]?J Clin Endocrinol Metab,2014,99(1):73-79.
[12]Tudela CM,Casey BM,Mc Intire DD,et al.Relationship of subclinical thyroid disease to the incidence of gestational diabetes[J].Obstet Gynecol,2012,119(5):983-988.
[13]Cleary-Goldman J,Malone FD,Lambert-Messerlian G,et al.Maternal thyroid hypofunction and pregnancy outcome[J].Obstet Gynecol,2008,112(1):85-92.
[14]Ashoor G,Maiz N,Rotas M,et al.Maternal thyroid function at 11-13weeks of gestation and spontaneous preterm delivery[J].Obstet Gynecol,2011,117(2 Pt 1):293-298.
[15]Ghafoor F,Mansoor M,Malik T,et al.Role of thyroid peroxidase antibodies in the outcome of pregnancy[J].J Coll Physicians Surg Pak,2006,16(7):468-471.
[16]Negro R,Schwartz A,Gismondi R,et al.Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes[J].J Clin Endocrinol Metab,2011,96(6):E920-924.
[17]Sahu MT,Das V,Mittal S,et al.Overt and subclinical thyroid dysfunction among indian pregnant women and its effect on maternal and fetal outcome[J].Arch Gynecol Obstet,2010,281(2):215-220.
[18]Matalon S,Sheiner E,Levy A,et al.Relationship of treated maternal hypothyroidism and perinatal outcome[J].J Reprod Med,2006,51(1):59-63.
[19]Cleary-Goldman J,Malone FD,Lambert-Messerlian G,et al.Maternal thyroid hypofunction and pregnancy outcome[J].Obstet Gynecol,2008,112(1):85-92.
[20]Ohashi M,Furukawa S,Michikata K,et al.Risk-based screening for thyroid dysfunction during pregnancy[J].J Pregnancy,2013,2013:619718.
[21]LeungAS,Millar LK,KooningsPP,MontoroM,MestmanJH.Perinatal outcome in hypothyroid pregnancies.Obstet Gynecol 1993;81:349-53.
[22]Wilson C.Endocrine disorders in pregnancy:updated guidelines for the management of thyroid disorders in pregnancy[J].Nat Rev Endocrinol,2012,8(11):624.
[23]M?nnist9 T,Mendola P,Reddy U,et al.Neonatal outcomes and birth weight in pregnancies complicated by maternal thyroid disease[J].Am J Epidemiol,2013,178(5):731-740.
[2]中华医学会内分泌学分会,中华医学会围产医学分会.妊娠和产后甲状腺疾病诊治指南[J].中华内分泌代谢杂志,2012,28(5):354-371.
[3]De Groot L,Abalovich M,Alexander EK,et al.Management of thyroid dysfunction during pregnancy and postpartum:an Endocrine Society clinical practice guideline[J].J Clin Endocrinol Metab,2012,97(8):2543-2565.
[4]Brent GA.The debate over thyroid-function screening in pregnancy[J].N Engl J Med,2012,366(6):562-563.
[5]Lazarus J,Brown RS,Daumerie C,et al.2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children[J].Eur Thyroid J,2014,3(2):76-94.
[6]张晓璐.妊娠期甲状腺疾病的临床流行病学调查[D].北京:首都医科大学,2013.
[7]Bliddal S,Boas M,Hilsted L,et al.Thyroid function and autoimmunity in Danish pregnant women after an iodine fortification program and associations with obstetric outcomes[J].Eur J Endocrinol,2015,173(6):709-718.
[8]Rashid M,Rashid MH.Obstetric management of thyroid disease[J].Obstet Gynecol Surv,2007,62(10):680-688.
[9]李元宾,滕卫平,单忠艳,等.妊娠中期妇女亚临床甲状腺异常对后代智力发育影响的研究[J].中华内分泌代谢杂志,2008,24(6):601-604.
[10]Gardosi J.New definition of small for gestational age based on fetal growth potential[J].Horm Res,2006,65 Suppl 3:15-18.
[11]Li CY,Shah ZY,Mao JY,et al.Assessment of thyroid function during first-trimester pregnancy:what is the rational upper limit of serum TSHduring the first trimester in Chinese pregnant women[J]?J Clin Endocrinol Metab,2014,99(1):73-79.
[12]Tudela CM,Casey BM,Mc Intire DD,et al.Relationship of subclinical thyroid disease to the incidence of gestational diabetes[J].Obstet Gynecol,2012,119(5):983-988.
[13]Cleary-Goldman J,Malone FD,Lambert-Messerlian G,et al.Maternal thyroid hypofunction and pregnancy outcome[J].Obstet Gynecol,2008,112(1):85-92.
[14]Ashoor G,Maiz N,Rotas M,et al.Maternal thyroid function at 11-13weeks of gestation and spontaneous preterm delivery[J].Obstet Gynecol,2011,117(2 Pt 1):293-298.
[15]Ghafoor F,Mansoor M,Malik T,et al.Role of thyroid peroxidase antibodies in the outcome of pregnancy[J].J Coll Physicians Surg Pak,2006,16(7):468-471.
[16]Negro R,Schwartz A,Gismondi R,et al.Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes[J].J Clin Endocrinol Metab,2011,96(6):E920-924.
[17]Sahu MT,Das V,Mittal S,et al.Overt and subclinical thyroid dysfunction among indian pregnant women and its effect on maternal and fetal outcome[J].Arch Gynecol Obstet,2010,281(2):215-220.
[18]Matalon S,Sheiner E,Levy A,et al.Relationship of treated maternal hypothyroidism and perinatal outcome[J].J Reprod Med,2006,51(1):59-63.
[19]Cleary-Goldman J,Malone FD,Lambert-Messerlian G,et al.Maternal thyroid hypofunction and pregnancy outcome[J].Obstet Gynecol,2008,112(1):85-92.
[20]Ohashi M,Furukawa S,Michikata K,et al.Risk-based screening for thyroid dysfunction during pregnancy[J].J Pregnancy,2013,2013:619718.
[21]LeungAS,Millar LK,KooningsPP,MontoroM,MestmanJH.Perinatal outcome in hypothyroid pregnancies.Obstet Gynecol 1993;81:349-53.
[22]Wilson C.Endocrine disorders in pregnancy:updated guidelines for the management of thyroid disorders in pregnancy[J].Nat Rev Endocrinol,2012,8(11):624.
[23]M?nnist9 T,Mendola P,Reddy U,et al.Neonatal outcomes and birth weight in pregnancies complicated by maternal thyroid disease[J].Am J Epidemiol,2013,178(5):731-740.