The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
J Clin Endocrinol Metab. 2018 Feb 1;103(2):778-789. doi: 10.1210/jc.2017-01560.
To investigate a dose dependency of thyroperoxidase antibody (TPOAb) concentrations in relation to thyroid function and premature delivery and define a population-based, pregnancy-specific, functional cutoff for TPOAb positivity.
Individual participant meta-analysis of three prospective birth cohorts: the Amsterdam Born Children and their Development study, and the Holistic Approach to Pregnancy.
Population-based studies in the Netherlands (2002 to 2014).
A total of 11,212 pregnant women (<20 weeks' gestation).
Thyrotropin (TSH) and FT4 concentrations, premature delivery.
In all cohorts, there was a dose-dependent positive association of TPOAb concentrations with TSH concentrations, as well as a dose-dependent negative association with FT4 concentrations during early pregnancy (all P < 0.0001). There was a dose-dependent association of TPOAb concentrations with the risk of premature delivery, which was also modified by TSH concentrations. Women with TPOAb concentrations from the 92nd percentile upward had a higher TSH and a higher risk of a TSH >2.5 mU/L (range, 19.4% to 51.3%). Stratified analyses showed that women with TPOAb concentrations below manufacturer cutoffs already had a higher risk of premature delivery, especially when TSH concentrations were high or in the high-normal range.
This study demonstrated a dose-dependent relationship between TPOAbs and thyroid function as well as the risk of premature delivery. Furthermore, our results indicate that the currently used cutoffs for TPOAb positivity may be too high. Furthermore, the use of a population-based cutoff for TPOAbs may identify women with a clinically relevant extent of thyroid autoimmunity and a higher risk of premature delivery but that would not be considered TPOAb positive or eligible for treatment otherwise.
研究甲状腺过氧化物酶抗体（TPOAb）浓度与甲状腺功能和早产的相关性及其剂量依赖性，并确定基于人群、妊娠特异性的 TPOAb 阳性功能切点。
对三项前瞻性出生队列的个体参与者进行荟萃分析：阿姆斯特丹出生儿童及其发育研究和整体妊娠方法。
荷兰的基于人群的研究（2002 年至 2014 年）。
共纳入 11212 名孕妇（<20 孕周）。
促甲状腺激素（TSH）和游离甲状腺素（FT4）浓度，早产。
在所有队列中，TPOAb 浓度与 TSH 浓度呈剂量依赖性正相关，与妊娠早期 FT4 浓度呈剂量依赖性负相关（均 P < 0.0001）。TPOAb 浓度与早产风险呈剂量依赖性相关，且与 TSH 浓度相关。TPOAb 浓度处于第 92 百分位以上的女性 TSH 更高，TSH >2.5 mU/L 的风险更高（范围 19.4%至 51.3%）。分层分析显示，TPOAb 浓度低于制造商界值的女性早产风险已经更高，尤其是 TSH 浓度较高或处于高正常范围时。
本研究表明 TPOAb 与甲状腺功能及早产风险之间存在剂量依赖性关系。此外，我们的结果表明，目前用于 TPOAb 阳性的切点可能过高。此外，使用基于人群的 TPOAb 切点可以识别出具有临床相关程度甲状腺自身免疫且早产风险更高的女性，但在其他情况下，这些女性不会被认为是 TPOAb 阳性或有资格接受治疗。
