Dose-dependency and a functional cut-off for TPO-antibody positivity during pregnancy.

Dose-dependency and a functional cut-off for TPO-antibody positivity during pregnancy.

J Clin Endocrinol Metab. 2017 Dec 12;:

Authors: Korevaar TIM, Pop VJ, Chaker L, Goddijn M, de Rijke YB, Bisschop PH, Broeren MA, Jaddoe VWV, Medici M, Visser TJ, Steegers EAP, Vrijkotte TG, Peeters RP

Abstract
Objective: To investigate a dose-dependency of TPOAb concentrations in relation to thyroid function and premature delivery, and define a population-based, pregnancy-specific, functional cut-off for TPOAb positivity.
Design: Individual participant meta-analysis of three prospective birth cohorts (Generation R, ABCD study and HAPPY study).
Setting: Population-based studies in the Netherlands (2002-2014).
Participants: 11 212 pregnant women (<20 weeks).
Main outcome measures: TSH and FT4 concentrations, premature delivery.
Results: In all cohorts, there was a dose-dependent positive association of TPOAb concentrations with TSH concentrations, and 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 upwards had a higher TSH and a higher risk of a TSH above 2.5 mU/L (range 19.4% to 51.3%). Stratified analyses showed that women with TPOAb concentrations below manufacturer cut-offs 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 cut-offs for TPOAb positivity may be too high. Furthermore, the use of a population-based cut-off for TPOAbs may identify women with a clinically relevant extent of thyroid autoimmunity and a higher risk or premature delivery, but that would not be considered TPOAb positive or eligible for treatment otherwise.

PMID: 29240902 [PubMed - as supplied by publisher]

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