Dose Dependency and a Functional Cutoff for TPO-Antibody Positivity During Pregnancy

作者：Korevaar Tim I. M.; Pop Victor J.; Chaker Layal; Goddijn Mariette; de Rijke Yolanda B.; Bisschop Peter H.; Broeren Maarten A.; Jaddoe Vincent W. V.; Medici Marco; Visser Theo J.; Steegers Eric A. P.; Vrijkotte Tanja G.; Peeters Robin P.

来源：Journal of Clinical Endocrinology & Metabolism, 2018, 103(2): 778-789.

DOI：10.1210/jc.2017-01560

Objective: 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.
Design: Individual participant meta-analysis of three prospective birth cohorts: the Amsterdam Born Children and their Development study, and the Holistic Approach to Pregnancy.
Setting: Population-based studies in the Netherlands (2002 to 2014).
Participants: A total of 11,212 pregnant women (<20 weeks' gestation).
Main Outcome Measures: Thyrotropin (TSH) and FT4 concentrations, premature delivery.
Results: 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.
Conclusions: 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.

• 出版日期2018-2