探讨先天性甲状腺功能减退症(CH)患儿确诊时间的影响因素。

选取2016年1月1日至2021年12月31日在成都市所有助产机构出生的促甲状腺激素(TSH)初筛结果为CH阳性或可疑阳性，并且成功召回复查的11 689例活产新生儿为研究对象。将其中679例确诊为CH患儿，根据确诊时间，分别纳入早诊CH组(n＝467，生后≤30 d确诊者)与晚诊CH组(n＝212，生后>30 d确诊者)。采用χ²检验与Wilcoxon秩和检验，比较2组患儿性别、是否为足月儿、出生季节，出生医院所在区域、性质与级别，是否在出生医院采集第2次足跟血进行复查，以及滤纸片干血斑标本(DBS)检测前周转时间、DBS检测报告周转时间、CH初筛可疑阳性患儿被召回时间。对这11 689例受试儿，绘制血清TSH水平初筛值预测其发生CH的受试者工作特征(ROC)曲线，并计算曲线下面积(AUC)与约登指数，分析血清TSH水平初筛值对患儿发生CH的预测价值。本研究遵循的程序符合电子科技大学医学院附属妇女儿童医院·成都市妇女儿童中心医院伦理委员会制定的伦理学标准，并得到该伦理委员会批准[审批文号：科研伦审2021(41)号)]。

①早诊CH组和晚诊CH组患儿性别、是否为足月儿、出生季节、出生医院性质及级别构成比等分别比较，差异均无统计学意义(P>0.05)。2组患儿出生医院所在区域及是否在出生医院采集第2次足跟血进行复查比较，差异均有统计学意义(χ²＝26.39、125.80，P<0.001)。②早诊CH组患儿DBS检测前周转时间、DBS检测报告周转时间、CH初筛可疑阳性患儿被召回时间分别为11 d(9 d，14 d)，6 d(5 d，7 d)，3 d(1 d，7 d)，均显著短于晚诊CH组的14 d(11 d，18 d)，7 d(6 d，7 d)，11 d(8 d，15 d)，并且差异均有统计学意义(Z＝－8.02、P<0.001，Z＝－2.61、P＝0.009，Z＝－15.35、P<0.001)。③对11 689例受试儿绘制血清TSH水平初筛值预测其发生CH的ROC曲线结果显示，其AUC为0.871(95%CI：0.825～0.886，P<0.001)，根据约登指数最大原则，血清TSH水平初筛值预测患儿发生CH的最佳临界值为14.7 μIU/mL，此时其预测患儿发生CH的敏感度为69.1%，特异度为93.4%，约登指数为62.5%。

CH新生儿出生医院位于郊区、CH初筛可疑阳性患儿被召回时间及DBS检测前周转时间长，可能造成CH确诊时间延误。成都市卫生行政部门应针对上述因素采取相应措施，缩短CH患儿确诊时间。建议将血清TSH水平初筛值14.7 μIU/mL作为CH筛查阳性临界值，可能更有利于缩短CH患儿确诊时间。

To explore the influencing factors of diagnosis time in infants with congenital hypothyroidism (CH).

A total of 11 689 live-born infants born in all midwifery institutions in Chengdu from January 1, 2016, to December 31, 2021, with positive or suspicious positive CH in initial thyroid stimulating hormone (TSH) screening and successfully recalled for re-examination were selected as the study subjects. Among them, 679 children with confirmed CH were divided into early-diagnosed CH group (n=467, diagnosed as CH ≤ 30 d after birth) and late-diagnosed CH group (n=212, diagnosed as CH > 30 d after birth). Chi-square test and Wilcoxon rank sum test were used to compare the gender, full-term delivery, birth season, location area, ownership and accreditation level of the birth hospital, whether the second blood spot sample for re-examination was collected at the birth hospital, as well as the turnaround time of dried blood spots on filter paper (DBS) before test, turnaround time of test report of DBS, and recall time for children with suspicious positive CH in CH initial screening. Among 11 689 infants, the receiver operating characteristic (ROC) curve of initial screening value of serum TSH was plotted to predict the risk of CH, and the area under curve (AUC) and Youden index were calculated to analyze the predictive value of initial screening value of serum TSH for the occurrence of CH. The procedures followed in this study complied with the ethical standards established by the Ethics Committee of Chengdu Women′s and Children′s Central Hospital, University of Electronic Science and Technology of China, and have been approved by the Ethics Committee [Approval No. 2021(41)].

① There were no significant differences in gender, full-term delivery, birth season, the ownership and accreditation level of birth hospital between early- and late-diagnosed CH group (P>0.05). The differences in location area of birth hospital, and whether the second blood spot sample for re-examination was collected at the birth hospital between two groups were statistically significant (χ²=26.39, 125.80; P<0.001). ②The turnaround time of DBS before test, turnaround time of test report of DBS, and recall time for children with suspicious positive CH in CH initial screening was 11 d (9 d, 14 d), 6 d (5 d, 7 d), and 3 d (1 d, 7 d) respectively in early-diagnosed CH group, all of which were shorter than those of late-diagnosed CH group at 14 d (11 d, 18 d), 7 d (6 d, 7 d), 11 d (8 d, 15 d), and all the differences were statistically significant (Z=-8.02, P<0.001; Z=-2.61, P=0.009; Z=-15.35, P<0.001). ③Among the 11 689 infants, result of ROC curve of initial screening value of serum TSH to predict CH in infants showed that the AUC was 0.871 (95%CI: 0.825-0.886, P<0.001). Based on the principal of maximum Youden index, the optimal cut-off value of initial screening value of serum TSH for predicting CH in infants was 14.7 μIU/mL, and the sensitivity, specificity and Youden index were 69.1%, 93.4% and 62.5%, respectively.

Infants with CH born in suburban hospital, with a longer recall time for suspicious positive CH in CH initial screening, and with a longer turnaround time of DBS before test may cause delay in the diagnosis of CH. Chengdu municipal health administrations should take corresponding measures for the above factors and shorten the time for diagnosing CH children. It is suggested to take the initial screening value of serum TSH 14.7 μIU/mL as the positive cut-off value for CH screening may be more conducive to shortening the time for diagnosing children with CH.