新生儿高促甲状腺素血症治疗决策及其影响因素

Treatment decision-making and influencing factors of neonatal hyperthyrotropinemia

摘要

目的 探究新生儿高促甲状腺素血症(hyperthyrotropinemia,HT)治疗决策及其影响因素,为是否采取治疗措施及治疗时机选择提供参考依据。方法 选择2014年6月1日至2024年6月1日在山西白求恩医院新生儿科住院的103例患儿为研究对象,根据是否需要左甲状腺素(L-T₄)治疗,分成自愈组(自行恢复至正常水平的患儿)和治疗组(需药物治疗恢复至正常)两组,采用多因素Logistic回归分析其治疗决策及影响因素,采用受试者工作特征(ROC)曲线及曲线下面积(AUC)分析预测价值。结果 与自愈组相比,治疗组患儿出生体重较低,初筛促甲状腺激素(TSH)浓度较高,呼吸窘迫史、剖宫产、合并妊娠期甲状腺功能减退症占比较高,差异均有统计学意义(Z/χ²值介于-3.582~8.005之间,P<0.05);多因素Logistic回归分析结果显示较高的初筛TSH浓度、剖宫产出生、母孕期合并甲状腺功能减退是HT患儿需要L-T₄治疗的独立危险因素(OR值分别为1.351、4.673、6.688,P<0.05),较高的出生体重为保护因素(OR=0.213,P<0.05);ROC曲线分析显示出生体重、初筛TSH浓度和两者联合预测的AUC分别为0.699、0.728、0.874,特异度分别为0.759、0.862、0.793,灵敏度分别为0.703、0.581、0.865。结论 自行恢复至正常甲状腺功能的高促甲状腺素血症患儿的出生体重较高,初筛促甲状腺激素浓度较低,两者联合可作为是否用药的参考指标。另外,临床上应重视剖宫产娩出、母孕期合并甲状腺功能减退症的新生儿的随访,必要时给予左甲状腺素治疗。

Abstract

Objective To investigate the treatment decision-making and influencing factors of neonatal hyperthyrotropinemia (HT),and to provide evidence for treatment indication assessment and timing selection. Methods A total of 103 neonates with HT who were hospitalized in the Department of Neonatology,Shanxi Bethune Hospital,from June 1,2014 to June 1,2024 were enrolled. According to whether levothyroxine (L-T₄) treatment was required,the patients were divided into a spontaneous recovery group (patients whose thyroid function returned to normal spontaneously) and a treatment group (patients requiring drug therapy to achieve normalization). Multivariate Logistic regression analysis was performed to identify treatment decision-making factors and influencing factors. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate predictive value. Results Compared with the spontaneous recovery group,neonates in the treatment group had lower birth weight,higher initial screening thyroid-stimulating hormone (TSH) concentrations,and higher proportions of respiratory distress history,cesarean delivery,and maternal hypothyroidism during pregnancy,with statistically significant differences (Z/χ ² values ranging from -3.582 to 8.005,P<0.05). Multivariate Logistic regression analysis showed that higher initial screening TSH concentration,cesarean delivery,and maternal hypothyroidism during pregnancy were independent risk factors for requiring L-T₄ treatment in neonates with HT (OR=1.351,4.673,and 6.688,respectively,P<0.05),whereas higher birth weight was a protective factor (OR=0.213,P<0.05). ROC curve analysis demonstrated that the AUCs of birth weight,initial screening TSH concentration,and their combined prediction were 0.699,0.728,and 0.874,respectively;the corresponding specificities were 0.759,0.862,and 0.793,and the sensitivities were 0.703,0.581,and 0.865,respectively. Conclusion Neonates with HT whose thyroid function normalized spontaneously tended to have higher birth weight and lower initial screening TSH concentrations. The combination of these two indicators may serve as a reference for medication decision-making. In addition,close follow-up should be emphasized for neonates delivered by cesarean section and those born to mothers complicated with hypothyroidism during pregnancy,and levothyroxine treatment should be administered when necessary.

关键词

新生儿 / 高促甲状腺素血症 / 药物治疗 / 影响因素

Key words

neonate / hyperthyrotropinemia / drug treatment / influencing factor

参考文献

[1] 中华预防医学会出生缺陷预防与控制专业委员会新生儿遗传代谢病筛查学组. 新生儿筛查遗传代谢病诊治规范专家共识[J]. 中华新生儿科杂志(中英文), 2023,38(7): 385-394.

[2] Chiesa A E, Tellechea M L. Update on neonatal isolated hyperthyrotropinemia:a systematic review[J]. Front Endocrinol (Lausanne), 2021,12: 643307.

[3] 孟祥慧, 徐书杭, 刘超. 先天性甲状腺功能减退症的筛查与诊治进展[J]. 中华内科杂志, 2020,59(9): 738-740.

[4] 张珈宁, 侯新琳. 先天性甲状腺功能减退症:2020-2021年欧洲儿科内分泌学学会和欧洲内分泌学学会共识指南更新[J]. 中华新生儿科杂志, 2022,37(3): 286-288.

[5] 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M].第5版/配增值. 北京: 人民卫生出版社, 2019.

[6] 张肖肖. 极早产儿及中期早产儿高促甲状腺素血症影响因素研究[D]. 承德: 承德医学院, 2021.

[7] 田强, 崔曙东. 枸橼酸咖啡因治疗辅助生殖技术后早产儿呼吸暂停的疗效观察[J]. 南京医科大学学报(自然科学版), 2018,38(12): 1790-1792.

[8] Zhuo L, Wang Z, Yang Y, et al. Obstetric and offspring outcomes in isolated maternal hypothyroxinaemia:a systematic review and meta-analysis[J]. J Endocrinol Invest, 2023,46(6): 1087-1101.

[9] Maraka S, Ospina N M, O'Keeffe D T, et al. Subclinical hypothyroidism in pregnancy:a systematic review and meta-analysis[J]. Thyroid, 2016,26(4): 580-590.

[10] LaFranchi S H. Thyroid function in preterm/low birth weight infants:impact on diagnosis and management of thyroid dysfunction[J]. Front Endocrinol (Lausanne), 2021,12: 666207.

[11] Hashemipour M, Hovsepian S, Ansari A, et al. Screening of congenital hypothyroidism in preterm,low birth weight and very low birth weight neonates:a systematic review[J]. Pediatr Neonatol, 2018,59(1): 3-14.

[12] 高巍, 方昆. 新生儿高促甲状腺素血症自然转归及治疗时机的临床研究[J]. 现代医药卫生, 2019,35(7): 1052-1054.

[13] Ramezani Tehrani F, Nazarpour S. Delivery factors and neonatal thyroid hormone levels:a systematic review[J]. J Pediatr Endocrinol Metab, 2021,34(7): 821-833.

[14] Aguiar L, Garb J, Reiter E, et al. Can one predict resolution of neonatal hyperthyrotropinemia?[J]. J Pediatr, 2016,174: 71-77.

[15] Adamczewska K, Adamczewski Z, Stasiak M, et al. Transient hyperthyrotropinemia in outpatient children treated due to acute infections of the respiratory system[J]. Int J Environ Res Public Health, 2021,18(8): 4115.

[16] Chen X, Jin B, Xia J, et al. Effects of thyroid peroxidase antibody on maternal and neonatal outcomes in pregnant women in an iodine-sufficient area in China[J]. Int J Endocrinol,2016,2016: 6461380.

[17] 梁丽玉. 新生儿高促甲状腺激素血症的危险因素分析[J]. 创伤与急诊电子杂志, 2021,9(4): 251-256.

[18] 齐志业, 张彩营, 王琼, 等. 新生儿高促甲状腺素血症与妊娠期甲状腺功能关系的病例对照研究[J]. 中国妇幼健康研究, 2022,33(8): 1-5.

[19] Garg R, Sait H, Jindal A, et al. Factors associated with transient neonatal hyperthyrotropinemia[J]. Indian J Pediatr, 2020,87(6): 482-483.

[20] Di Dalmazi G, Carlucci M A, Semeraro D, et al. A detailed analysis of the factors influencing neonatal TSH:results from a 6-year congenital hypothyroidism screening program[J]. Front Endocrinol (Lausanne), 2020,11: 456.

[21] Cortés-Castell E, Juste M, Palazón-Bru A, et al. Factors associated with moderate neonatal hyperthyrotropinemia[J]. PLoS One, 2019,14(7): e0220040.

[22] Grob F, Van Vliet G. Avoiding the overdiagnosis of congenital hypothyroidism in premature newborns[J]. Pediatrics, 2019,144(2): e20191706.

[23] Kaluarachchi D C, Colaizy T T, Pesce L M, et al. Congenital hypothyroidism with delayed thyroid-stimulating hormone elevation in premature infants born at less than 30 weeks gestation[J]. J Perinatol, 2017,37(3): 277-282.

[24] Rasoulizadeh Z, Ordooei M, Akbarian E. Diagnostic options,physiopathology,risk factors and genetic causes of permanent congenital hypothyroidism:a narrative review[J]. Caspian J Intern Med, 2024,15(4): 570-578.