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

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

Research output: Contribution to journalArticleScientificpeer-review

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 (

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.

Original languageEnglish
Pages (from-to)778–789
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number2
DOIs
Publication statusPublished - 2018

Fingerprint

Antibodies
Thyrotropin
Autoimmunity
Netherlands
Dependency (Psychology)

Keywords

  • AMERICAN THYROID ASSOCIATION
  • DISEASE
  • GENERATION R
  • LEVOTHYROXINE TREATMENT
  • MANAGEMENT
  • PROSPECTIVE COHORT
  • REFERENCE INTERVALS
  • RISK
  • SUBCLINICAL HYPOTHYROIDISM
  • WOMEN

Cite this

Korevaar, T. I. M., Pop, V. J. M., Chaker, L., Goddijn, M., De Rijke, Y. B., Bisschop, P. H., ... Peeters, R. P. (2018). Dose dependency and a functional cut-off for TPO-antibody positivity during pregnancy. Journal of Clinical Endocrinology and Metabolism, 103(2), 778–789. https://doi.org/10.1210/jc.2017-01560
Korevaar, Tim I M ; Pop, V.J.M. ; 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. / Dose dependency and a functional cut-off for TPO-antibody positivity during pregnancy. In: Journal of Clinical Endocrinology and Metabolism. 2018 ; Vol. 103, No. 2. pp. 778–789.
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title = "Dose dependency and a functional cut-off for TPO-antibody positivity during pregnancy",
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 (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.",
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author = "Korevaar, {Tim I M} and V.J.M. Pop and Layal Chaker and Mariette Goddijn and {De Rijke}, {Yolanda B} and Bisschop, {Peter H} and Broeren, {Maarten A} and Jaddoe, {Vincent W V} and Marco Medici and Visser, {Theo J} and Steegers, {Eric A P} and Vrijkotte, {Tanja G} and Peeters, {Robin P}",
year = "2018",
doi = "10.1210/jc.2017-01560",
language = "English",
volume = "103",
pages = "778–789",
journal = "Journal of Clinical Endocrinology and Metabolism",
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publisher = "ENDOCRINE SOC",
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}

Korevaar, TIM, Pop, VJM, Chaker, L, Goddijn, M, De Rijke, YB, Bisschop, PH, Broeren, MA, Jaddoe, VWV, Medici, M, Visser, TJ, Steegers, EAP, Vrijkotte, TG & Peeters, RP 2018, 'Dose dependency and a functional cut-off for TPO-antibody positivity during pregnancy', Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 2, pp. 778–789. https://doi.org/10.1210/jc.2017-01560

Dose dependency and a functional cut-off for TPO-antibody positivity during pregnancy. / Korevaar, Tim I M; Pop, V.J.M.; 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.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 2, 2018, p. 778–789.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Dose dependency and a functional cut-off for TPO-antibody positivity during pregnancy

AU - Korevaar, Tim I M

AU - Pop, V.J.M.

AU - Chaker, Layal

AU - Goddijn, Mariette

AU - De Rijke, Yolanda B

AU - Bisschop, Peter H

AU - Broeren, Maarten A

AU - Jaddoe, Vincent W V

AU - Medici, Marco

AU - Visser, Theo J

AU - Steegers, Eric A P

AU - Vrijkotte, Tanja G

AU - Peeters, Robin P

PY - 2018

Y1 - 2018

N2 - 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 (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.

AB - 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 (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.

KW - AMERICAN THYROID ASSOCIATION

KW - DISEASE

KW - GENERATION R

KW - LEVOTHYROXINE TREATMENT

KW - MANAGEMENT

KW - PROSPECTIVE COHORT

KW - REFERENCE INTERVALS

KW - RISK

KW - SUBCLINICAL HYPOTHYROIDISM

KW - WOMEN

U2 - 10.1210/jc.2017-01560

DO - 10.1210/jc.2017-01560

M3 - Article

VL - 103

SP - 778

EP - 789

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -