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J Clin Endocrinol Metab. 2018 Feb 1;103(2):778-789. doi: 10.1210/jc.2017-01560.

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

Author information

1
The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands.
2
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
3
Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, the Netherlands.
4
Sophia Children's Hospital, Rotterdam, the Netherlands.
5
Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands.
6
Department of Reproductive Medicine, Academic Medical Center, Amsterdam, the Netherlands.
7
Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, the Netherlands.
8
Department of Endocrinology, Academic Medical Center, Amsterdam, the Netherlands.
9
Laboratory of Clinical Chemistry and Haematology, Máxima Medical Centre, Veldhoven, the Netherlands.
10
Department of Pediatrics, Erasmus Medical Center, Rotterdam, the Netherlands.
11
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
12
Department of Obstetrics and Gynaecology, Erasmus Medical Center, Rotterdam, the Netherlands.
13
Department of Public Health, Academic Medical Center, Amsterdam, the Netherlands.

Abstract

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.

PMID:
29240902
DOI:
10.1210/jc.2017-01560
[Indexed for MEDLINE]

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