孕早期单纯甲状腺过氧化物酶抗体阳性与胎儿生长的关联

doi:10.19723/j.issn.1671-167X.2023.05.017

摘要/Abstract

摘要：

目的: 研究孕早期单纯甲状腺过氧化物酶抗体(thyroid peroxidase antibody, TPOAb)阳性与胎儿生长的关联。方法: 采用出生队列研究设计, 选取末次月经在2016年5月至2019年4月且在北京市通州区妇幼保健院分娩的16 446名单胎孕妇, 按照孕早期甲状腺功能状态分为单纯TPOAb阳性组(n=1 654)和甲状腺功能正常组(n=14 792)。三次超声测量胎儿生长指标由超声科医生在常规产前超声检查时按照统一方法测量得到, 采用基于位置、尺度、形状参数的广义加性模型, 校正胎龄及性别计算超声测量胎儿生长指标Z评分, 胎儿生长结局指标包括预测胎儿体质量、腹围、双顶径(biparietal diameter, BPD)、股骨长和头围的Z评分以及胎儿生长受限。采用广义估计方程分析单纯TPOAb阳性与多次重复测量的胎儿生长结局指标的关联。对广义估计方程分析中有统计学意义的关联结果, 进一步采用广义线性模型分析单纯TPOAb阳性与不同孕周的结局指标之间的关联。结果: 三次超声测量孕周中位数分别为23.6(23.3, 24.1)、30.3(29.7, 30.9)和37.3(37.0, 37.7)周。单纯TPOAb阳性组BPD的Z评分比甲状腺功能正常组高0.057(95%CI: 0.014~0.100, P=0.009)。进一步根据孕周进行分层分析, 结果比较稳定(P＜0.05), 与甲状腺功能正常组相比较, 单纯TPOAb阳性组BPD的Z评分在21~25孕周高0.052, 在29~32孕周高0.055, 在36~40孕周高0.068。单纯TPOAb阳性组与甲状腺功能正常组预测胎儿体质量、腹围、股骨长和头围的Z评分以及胎儿生长受限的差异没有统计学意义(P>0.05)。结论: 孕早期单纯TPOAb阳性略微增宽胎儿BPD, 但未见其影响其他生长指标, 该结果的可重复性与实际意义有待确定。

关键词: 甲状腺过氧化物酶抗体, 妊娠初期, 胎儿发育, 甲状腺疾病

Abstract:

Objective: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. Methods: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. Results: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. Conclusion: The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.

Key words: Thyroid peroxidase antibody, Pregnancy trimester, first, Fetal development, Thyroid di-seases

中图分类号:

R714.256

徐金辉,韩娜,苏涛,林力孜,计岳龙,周双,包鹤龄,刘峥,罗树生,徐相蓉,王海俊. 孕早期单纯甲状腺过氧化物酶抗体阳性与胎儿生长的关联[J]. 北京大学学报（医学版）, 2023, 55(5): 886-892.

Jin-hui XU,Na HAN,Tao SU,Li-zi LIN,Yue-long JI,Shuang ZHOU,He-ling BAO,Zheng LIU,Shu-sheng LUO,Xiang-rong XU,Hai-jun WANG. Association of maternal isolated thyroid peroxidase antibody positive in the first trimester with fetal growth[J]. Journal of Peking University (Health Sciences), 2023, 55(5): 886-892.

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Items	Isolated TPOAb positive (n=1 654)	Euthyroid(n=14 792)	P value
Maternal age/years	29.6 (27.2, 32.6)	29.4 (27.1, 32.2)	0.021
Maternal education levels			0.005
Low (high school and below)	232 (14.0)	2 299 (15.5)
Middle (vocational college)	670 (40.5)	6 378 (43.1)
High (university and above)	752 (45.5)	6 115 (41.3)
Current employment status			0.115
Yes	1 479 (89.4)	13 027 (88.1)
No	175 (10.6)	1 765 (11.9)
Parity			0.918
Primipara	925 (55.9)	8 297 (56.1)
Multipara	729 (44.1)	6 495 (43.9)
Pre-pregnancy BMI			0.637
Underweight	165 (10.0)	1 443 (9.8)
Normal weight	1 052 (63.6)	9 599 (64.9)
Overweight	348 (21.0)	2 928 (19.8)
Obesity	89 (5.4)	822 (5.6)
Gestational age at thyroid function testing/weeks	9.0 (8.0, 10.1)	9.0 (8.0, 10.3)	0.623
TSH/(mIU/L)	1.1 (0.7, 1.6)	0.9 (0.5, 1.3)	＜ 0.001
FT4/(pmol/L)	13.5 (12.5, 14.7)	13.6 (12.7, 14.8)	＜ 0.001

Items	21-25 weeks		29-32 weeks		36-40 weeks
Items	Euthyroid (n=14 285)	Isolated TPOAb positive (n=1 606)	Euthyroid (n=14 037)	Isolated TPOAb positive (n=1 569)	Euthyroid (n=11 466)	Isolated TPOAb positive (n=1 273)
EFW/g	614.79±68.02	614.98±66.39	1529.19±181.38	1531.23±183.37	2935.17±305.42	2949.79±318.00
Z-score	-0.14±0.99	-0.13±0.98	0.00±0.99	0.00±0.99	-0.04±0.98	-0.01±1.00
AC/cm	19.07±0.92	19.08±0.92	26.11±1.27	26.14±1.28	33.04±1.54	33.10±1.59
Z-score	-0.02±0.98	0.00±0.99	-0.01±0.99	0.00±0.99	-0.03±0.98	0.00±1.00
BPD/cm	5.80±0.29	5.82±0.29	7.74±0.33	7.76±0.34	9.14±0.32	9.16±0.32
Z-score	-0.02±0.99	0.03±0.99	-0.01±0.99	0.05±1.00	-0.03±0.98	0.04±0.99
FL/cm	4.13±0.19	4.13±0.19	5.65±0.23	5.64±0.24	6.86±0.22	6.86±0.23
Z-score	-0.02±0.99	-0.03±0.98	0.00±0.99	-0.06±0.99	-0.02±0.98	-0.03±1.00
HC/cm	21.45±0.86	21.44±0.87	28.07±1.01	28.12±1.05	32.46±1.03	32.54±1.04
Z-score	-0.02±0.99	-0.01±0.99	-0.01±0.98	0.04±0.99	-0.03±0.98	0.04±0.99
FGR/%	607 (4.3)	62 (3.9)	535 (3.8)	57 (3.6)	407 (3.6)	52 (4.1)

Items	Adjust model 1		Adjusted model 2
Items	β or RR (95%CI)	P value	β or RR (95%CI)	P value
EFW	0.007 (-0.036, 0.049)	0.760	0.012 (-0.031, 0.055)	0.590
AC	0.016 (-0.025, 0.057)	0.451	0.020 (-0.022, 0.061)	0.349
BPD	0.054 (0.011, 0.097)	0.013	0.057 (0.014, 0.100)	0.009
FL	-0.026 (-0.068, 0.016)	0.224	-0.020 (-0.062, 0.023)	0.358
HC	0.028 (-0.013, 0.070)	0.183	0.031 (-0.011, 0.073)	0.148
FGR	1.02 (0.85, 1.21)	0.862	1.01 (0.84, 1.21)	0.922

Items	Adjust model 1		Adjusted model 2
Items	β (95%CI)	P value	β (95%CI)	P value
21-25 weeks	0.049 (-0.001, 0.100)	0.056	0.052 (0.001, 0.103)	0.044
29-32 weeks	0.049 (-0.002, 0.100)	0.060	0.055 (0.004, 0.107)	0.035
36-40 weeks	0.066 (0.010, 0.123)	0.022	0.068 (0.011, 0.125)	0.020

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