季节与地域变化对新生儿TSH的影响及切值调整研究

葛丽莎; 潘小莉; 潘澍青; 潘云; 李海波; 庄丹燕

doi:10.16766/j.cnki.issn.1674-4152.004453

季节与地域变化对新生儿TSH的影响及切值调整研究

doi: 10.16766/j.cnki.issn.1674-4152.004453

宁波大学附属妇女儿童医院出生缺陷综合防治中心宁波市胚胎源性疾病防治重点实验室宁波市基因组医学与出生缺陷防治重点实验室，浙江宁波 315012

基金项目:

宁波市科技计划项目 2022S035

宁波市医疗卫生高端团队重大攻坚项目 2022020405

浙江省医药卫生科技计划项目 2023KY1121

详细信息

通讯作者:
庄丹燕，E-mail: nbsclab@126.com

中图分类号: R541
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出版历程
- 收稿日期: 2025-08-11

Research on the effect of seasonal and regional variations on neonatal TSH and the adjustment of TSH Cut-off

Ningbo University Affiliated Women and Children ' s Hospital Center for Comprehensive Prevention and Control of Birth Defects, Ningbo, Ningbo Key Laboratory for Embryonic Origin Diseases Prevention and Control, Ningbo Key Laboratory for Genomic Medicine and Birth Defects Prevention and Control, Ningbo, Zhejiang 315012, China

摘要

摘要: 目的分析地域和季节变化对新生儿促甲状腺激素(TSH)的影响，建立切合宁波地区实际的新生儿先天性减退症(CH)筛查的促甲状腺激素(TSH)切值，以指导本地区CH筛查。方法回顾性分析2019年1月—2023年12月在宁波地区出生的310 791例新生儿的TSH值。按宁波大市10个县市区的海岸线长短分为沿海组和内陆组，按出生季节分为春、夏、秋和冬4个组，分析地域和季节变化对TSH的影响。采用百分位数法和ROC曲线法计算切值，并结合不同切值下的筛查效能，建立符合本地区CH筛查的TSH切值。结果 310791例新生儿中，初筛阳性11359例，确诊CH 328例，高TSH 492例。沿海组TSH初筛阳性率和CH发病率均高于内陆组，差异有统计学意义(P＜0.05)。冬季TSH初筛阳性率和CH发病率均高于其他三季，差异有统计学意义(P＜0.05)。百分位数法所得四季的TSH切值分别为9.0、8.5、8.8和10.4 mIU/L，比原有切值下多漏筛52、57、59和100例；ROC曲线法所得四季的TSH切值分别为6.4、7.0、6.9和6.4 mIU/L，除春季比原有切值下多检出4例患儿，其余检出与原有切值检出患儿均一致。结论宁波地区新生儿CH发病率为0.11%，高于中国其他地区；宁波地区新生儿TSH值受地域和季节影响，以沿海和冬季较高；结合本实验室筛查效率和实际可操作性，最终确定切值为7.0 mIU/L。
- 新生儿 /
- 先天性减退症 /
- 促甲状腺激素 /
- 切值
Abstract: Objective Analyzing the influence of geographical and seasonal variations on neonatal thyroid-stimulating hormone (TSH) levels to establish a regionally appropriate TSH cut-off for neonatal congenital hypothyroidism (CH) screening in Ningbo, thereby guiding local CH screening practices. Methods The TSH of 310 791 newborns born in Ningbo from January 2019 to December 2023 were retrospectively analyzed. According to the coastline length of the 10 counties in Ningbo city, they were divided into coastal and inland groups, and then further divided into four groups according to the birth season: spring, summer, autumn, and winter. Percentile method and ROC curve analysis were used to calculate the cut-off and establish the TSH cut-off conforming to the local CH screening. Results Among 310 791 newborns screened, 11 359 cases were initially positive. 328 cases were confirmed as CH, and 492 cases were diagnosed with hyperthyrotropinemia. The positive rate of TSH screening and the incidence of CH in the coastal group were higher than those in the inland group, and the difference was statistically significant (P < 0.05). The positive rate of TSH and the incidence of CH in winter were higher than those in the other three seasons, and the difference was statistically significant (P < 0.05). The TSH cutoff values determined by the percentile method for the four seasons were 9.0, 8.5, 8.8, and 10.4 mIU/L, which would result in 52, 57, 59, and 100 additional missed cases, respectively, compared with the original cutoff. In contrast, the cutoff values derived from the ROC curve method were 6.4, 7.0, 6.9, and 6.4 mIU/L for the four seasons. Except for the spring season, where four additional cases were detected compared to the original cutoff, the number of cases identified in the other seasons remained consistent with that of the original cutoff. Conclusion The incidence of CH in newborns was 0.11%, which was higher than that in other parts of China. The TSH values in the Ningbo area were affected by region and season, and were higher in the coastal area and winter. The cut-off was determined to be 7.0 mIU/L based on the laboratory screening efficiency and the actual operability.
- Newborn /
- Congenital hypothyroidism /
- Thyroid stimulating hormone /
- Cut-off
利益冲突 无

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表 1 2019—2023年新生儿CH发病率统计分析[例(%)]

Table 1. Statistical analysis of the incidence of congenital hypothyroidism in neonates from 2019 to 2023 [cases (%)]

年份	筛查	初筛阳性	CH	高TSH
2019	78 165	2 442(3.12)	57(0.07)	76(0.10)
2020	63 888	2 546(3.99)	70(0.11)	90(0.14)
2021	59 533	2 068(3.47)	70(0.12)	99(0.17)
2022	56 587	1 946(3.44)	52(0.09)	91(0.16)
2023	52 618	2 357(4.48)	79(0.15)	136(0.26)
χ²值		196.950	19.732	53.337
P值		＜0.001	0.001	＜0.001

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表 2 不同地区新生儿TSH筛查情况分析

Table 2. Analysis of neonatal TSH screening in different regions

地区	筛查例数	TSH[M(P₂₅, P₇₅), mIU/L]	初筛阳性[例(%)]	CH[例(%)]	高TSH[例(%)]	漏筛[例(‰)]
地区	筛查例数	TSH[M(P₂₅, P₇₅), mIU/L]	初筛阳性[例(%)]	CH[例(%)]	高TSH[例(%)]	CH	高TSH
内陆组	192 247	2.1(1.3，3.3)	4 992(2.60)	177(0.09)	246(0.13)	5(0.03)	22(0.11)
沿海组	118 544	2.7(1.6，4.2)	6 367(5.37)	141(0.12)	203(0.17)	5(0.04)	21(0.18)
统计量		-89.760^a	1 602.837^b	5.181^b	9.523^b	0.596^b	2.085^b
P值		＜0.001	＜0.001	0.023	0.002	0.520	0.158
注：^a为Z值，^b为χ²值。

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表 3 不同季节新生儿TSH筛查情况分析

Table 3. Analysis of neonatal TSH screening in different seasons

季节	筛查例数	TSH[M(P₂₅, P₇₅), mIU/L]	初筛阳性[例(%)]	CH [例(%)]	高TSH [例(%)]	漏筛[例(‰)]
季节	筛查例数	TSH[M(P₂₅, P₇₅), mIU/L]	初筛阳性[例(%)]	CH [例(%)]	高TSH [例(%)]	CH	高TSH
春季	74 891	2.3(1.4，3.6)	2548(3.40)	71(0.09)	92(0.12)	3(0.04)	14(0.19)
夏季	80 377	2.2(1.3，3.4)	2023(2.52)	78(0.10)	103(0.13)	5(0.06)	12(0.15)
秋季	81 921	2.2(1.3，3.5)	2500(3.05)	72(0.09)	115(0.14)	1(0.01)	9(0.11)
冬季	73 602	2.7(1.6，4.2)	4288(5.83)	97(0.13)	139(0.19)	1(0.01)	8(0.11)
统计量		3 686.289^a	1 379.016^b	8.555^b	14.058^b	5.076^b	2.296^b
P值		＜0.001	＜0.001	0.036	0.003	0.166	0.513
注：春季为3、4、5月；夏季为6、7、8月；秋季为9、10、11月；冬季为12、1、2月。^a为Z值，^b为χ²值。

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表 4 不同季节新生儿TSH切值分析(百分位数法)

Table 4. Analysis of neonatal TSH cutoff values in different seasons (percentile method)

季节	P₂₅	P₅₀	P₇₅	P₉₀	P₉₅	P₉₆	P₉₇	P₉₈	P_98.5	P₉₉
春季	1.4	2.3	3.6	5.2	6.2	6.5	7.0	7.8	8.3	9.0
夏季	1.3	2.2	3.4	4.9	5.9	6.2	6.5	7.2	7.8	8.5
秋季	1.3	2.2	3.5	5.0	6.1	6.3	7.0	7.5	8.0	8.8
冬季	1.6	2.7	4.2	5.9	7.1	7.5	8.1	8.9	9.5	10.4
合计	1.4	2.3	3.7	5.3	6.3	6.6	7.2	7.9	8.9	9.2

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表 5 不同季节新生儿TSH切值分析(ROC曲线法)

Table 5. Analysis of neonatal TSH cutoff values in different seasons (ROC curve method)

季节	切值(mIU/L)	灵敏度	1-特异度	约登指数	AUC
春季	6.4	0.928	0.043	0.885	0.973
夏季	7.0	0.914	0.023	0.891	0.965
秋季	6.9	0.949	0.028	0.921	0.984
冬季	6.4	0.928	0.043	0.885	0.973
合计	6.8	0.937	0.035	0.902	0.974

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表 6 新生儿TSH切值的筛查效能分析

Table 6. Analysis of screening performance of neonatal TSH cutoff values

季节	方法	切值(mIU/L)	真阳性(例)	假阳性(例)	真阴性(例)	假阴性(例)	PPV(%)	灵敏度(%)	特异度(%)	漏筛率(‰)
春季	原切值	7.0	163	2 385	72 326	17	6.52	90.56	96.81	0.23
	ROC	6.4	167	3 232	71 479	13	4.91	92.78	95.67	0.17
	P₉₉	9.0	111	674	74 307	69	14.14	61.67	99.46	0.92
夏季	原切值	7.0	181	1 842	78 337	17	8.94	91.41	97.70	0.21
	ROC	7.0	181	1 842	78 337	17	8.94	91.41	97.70	0.21
	P₉₉	8.5	124	681	79 498	74	15.40	62.63	99.15	0.92
秋季	原切值	7.0	187	2 313	79 411	10	7.48	94.92	97.17	0.12
	ROC	6.9	187	2 313	79 411	10	7.48	94.92	97.17	0.12
	P₉₉	8.8	128	713	81 011	69	15.22	64.97	99.13	0.84
冬季	原切值	7.0	236	4 052	69 305	9	5.50	96.33	94.47	0.12
	ROC	6.4	236	5 301	68 056	9	4.26	96.33	92.77	0.12
	P₉₉	10.4	136	617	72 740	109	18.06	55.51	99.16	1.48
合计	原切值	7.0	767	10 592	299 379	53	6.75	93.54	96.58	0.17
	ROC	6.8	768	10 722	299 249	52	6.68	93.66	96.54	0.17
	P₉₉	9.2	499	2 766	307 205	321	15.28	60.85	99.11	1.03
	拟使用值	6.0	777	19 331	290 640	43	3.86	94.76	93.76	0.14
		6.5	771	13 115	296 856	49	5.55	94.02	95.77	0.16
		7.5	666	7 298	302 161	154	8.36	81.22	97.86	0.50
注：PPV为阳性预测值。

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表 7 不同切值下CH和高TSH血症确诊和漏筛情况分析

Table 7. Analysis of confirmed cases and missed screenings of congenital hypothyroidism and hyperthyrotropinemia under different cutoff values

切值	初筛阳性[例(%)]	CH确诊[例(‰)]	高TSH确诊[例(‰)]	CH漏筛[例(‰)]	高TSH漏筛[例(‰)]
6.0	20 108(6.47)	320(1.03)	457(1.47)	8(0.03)	35(0.11)
6.5	13 886(4.47)	318(1.02)	453(1.46)	10(0.03)	39(0.13)
7.0	11 359(3.65)	318(1.02)	449(1.44)	10(0.03)	43(0.14)
7.5	7 964(2.56)	286(0.92)	380(1.22)	42(0.14)	112(0.36)
8.0	6 067(1.95)	268(0.86)	330(1.06)	60(0.19)	162(0.52)

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