Pregnancy-specific reference intervals for TSH and FT4: novel insights from preconception-gestation longitudinal data

Leonie T L Warringa; Joris A J Osinga; Arash Derakhshan; Vincent W V Jaddoe; Sjoerd A A van den Berg; Robin P Peeters; Tim I M Korevaar

doi:10.1210/clinem/dgag082

Pregnancy-specific reference intervals for TSH and FT4: novel insights from preconception-gestation longitudinal data

J Clin Endocrinol Metab. 2026 Feb 28:dgag082. doi: 10.1210/clinem/dgag082. Online ahead of print.

Authors

Leonie T L Warringa^{1

2}, Joris A J Osinga^{1

2}, Arash Derakhshan^{1

2}, Vincent W V Jaddoe^{2

3}, Sjoerd A A van den Berg⁴, Robin P Peeters^{1

2}, Tim I M Korevaar^{1

2

5}

Affiliations

¹ Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.
² The Generation R study Group, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.
³ Department of Paediatrics, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.
⁴ Department of Clinical Chemistry, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.
⁵ Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, 3000 CA, Rotterdam, the Netherlands.

PMID: 41762673
DOI: 10.1210/clinem/dgag082

Abstract

Background: Pregnancy-specific changes in thyroid physiology have prompted the use of pregnancy-specific reference intervals to diagnose thyroid disease. However, such reference intervals are not widely available, and there is no evidence of their superiority over non-pregnancy reference intervals. Preconception data are understudied benchmarks to compare pregnancy-specific and non-pregnancy-specific intervals. Moreover, the added value of FT3 measurements, for example in cases of (subclinical) hyperthyroidism, remains to be quantified.

Methods: This study was embedded within Generation R Next, a population-based prospective cohort from preconception through postpartum in Rotterdam. Prevalence of thyroid disease entities was assessed using both pregnancy-specific and non-pregnancy reference intervals during pregnancy, and using non-pregnancy reference intervals in the preconception period. FT3 concentrations of both euthyroid participants and those with thyroid disease entities were compared in the preconception period and during pregnancy.

Results: The study population included 1,058 women during preconception and 2,084 women during pregnancy. The prevalence of subclinical hypothyroidism during pregnancy was 1.5% with use of non-pregnancy reference intervals and 3.6% with pregnancy-specific reference intervals, versus 2.2% during preconception. The prevalence of subclinical hyperthyroidism during pregnancy was 11.1% with use of non-pregnancy reference intervals and 1.5% with pregnancy-specific reference intervals, versus 2.0% during preconception. Additional FT3 measurements would reclassify 5.6% of subclinical hyperthyroidism cases to hyperthyroidism during preconception and 14.3% during pregnancy.

Conclusion: This is the first study to assess the prevalence of (sub)clinical thyroid disease during pregnancy comparing non-pregnancy and pregnancy-specific reference intervals, while also comparing these prevalences to preconception data from the same source population. We show that pregnancy-specific reference intervals likely result in overdiagnosis of subclinical hypothyroidism and that FT3 has limited value in diagnosing (sub)clinical thyroid disease during pregnancy.

Keywords: Preconception; Pregnancy; Reference values; Thyroid Function Tests; Thyrotropin; Thyroxine.