Thyroid Peroxidase Antibodies and Prospective Live Birth Rate: A Cohort Study of Women with Recurrent Pregnancy Loss
Open accessAbstract
Background: Thyroid autoimmunity has been associated with pregnancy loss. Suggested mechanisms include thyroid function aberrations or an underlying breach of immunotolerance. We hypothesized that thyroid autoimmunity is a marker of the latter in women with recurrent pregnancy loss. This study investigated thyroid peroxidase antibody (TPOAb) status as a predictor of live birth in women with unexplained recurrent pregnancy loss. Methods: Cohort study of 825 consecutive women with recurrent pregnancy loss followed at the tertiary referral center for Recurrent Pregnancy Loss, Copenhagen University Hospital (Rigshospitalet), from 2011 to 2017. Recurrent pregnancy loss was defined as ≥3 consecutive losses, and as unexplained by absence of antiphospholipid syndrome, parental chromosome abnormality, or uterus malformation. Upon first visit, all women were screened for thyrotropin (TSH) and TPOAbs (TPOAb positivity: ≥60 kIU/L). Adjusted logistic regression analyses included as covariates the following: maternal age, TSH, previous number of losses, body mass index, smoking, pregnancy achieved by assisted reproductive technology, and thyroxine replacement (T4) treatment. Results: We included 825 women with a total of 3246 previous losses, of whom 139 (16.8%) were TPOAb positive. TPOAb positivity was not associated with the previous number of losses ( p = 0.41). Women with unexplained recurrent pregnancy loss had a live birth rate in the first pregnancy after referral of 62.8% (285 of 454). TPOAb positivity was found in 78 of 454 (17.2%) women and was associated with a reduced live birth rate (51.3% vs. 65.2%, p = 0.02, adjusted odds ratio [aOR] 0.2 [0.1–0.6] p = 0.001). Treatment with T4 increased live birth rate significantly (aOR 3.7 [1.4–9.8], p = 0.007), and TPOAb-positive women receiving T4 had a live birth rate similar to that of TPOAb-negative women not receiving T4 ( p = 0.70). Only 30% of TPOAb-positive women and 39% of women treated with T4 during pregnancy had known thyroid disease at referral. Conclusion: In a large cohort of women with unexplained recurrent pregnancy loss, TPOAb positivity was predictive of a reduced live birth rate. However, T4 treatment improved odds of live birth. The study supports screening for TPOAbs as a risk factor in women with unexplained recurrent pregnancy loss. The beneficial effect of T4 treatment in this high-risk group needs confirmation by randomized controlled trials. Close collaboration between fertility experts and endocrinologists is paramount.
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In young fertile women, undertreatment with levothyroxine is associated with recurrent pregnancy loss.
“In young fertile women, the consequences of undertreatment with LT4 are subnormal fertility, recurrent pregnancy loss, compromised fetal growth, and neurocognitive development.”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [24]
In young fertile women, undertreatment with levothyroxine is associated with compromised fetal growth.
“In young fertile women, the consequences of undertreatment with LT4 are subnormal fertility, recurrent pregnancy loss, compromised fetal growth, and neurocognitive development.”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [24]
In young fertile women, undertreatment with levothyroxine is associated with compromised neurocognitive development.
“In young fertile women, the consequences of undertreatment with LT4 are subnormal fertility, recurrent pregnancy loss, compromised fetal growth, and neurocognitive development.”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [24]
In pregnancy, levothyroxine treatment is important to secure sufficient placental transfer of T4, needed for fetal development and to reduce adverse pregnancy outcomes such as pregnancy loss and preterm birth.
“Specifically in pregnancy, the LT4 treatment is not only important to the woman, but also to secure a sufficient placental transfer of T4, which is needed for fetal development and to reduce adverse pregnancy outcomes such as pregnancy loss and preterm birth [23, 24].”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [24]
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Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art
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Risks of suboptimal and excessive thyroid hormone replacement across ages
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“Specifically in pregnancy, the LT4 treatment is not only important to the woman, but also to secure a sufficient placental transfer of T4, which is needed for fetal development and to reduce adverse pregnancy outcomes such as pregnancy loss and preterm birth [23, 24].”
BackgroundSelf-citation
- Authors
- Bliddal, S., Feldt-Rasmussen, U., Rasmussen, Å. K., Kolte, A. M., Hilsted, L. M., Christiansen, O. B., Nielsen, C. H., & Nielsen, H. S.
- Affiliations
- Copenhagen University Hospital (DK)
- Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- Aalborg University Hospital (DK)
- Corresponding author
- Bliddal, Sofie
- ORCID
- Venue
- Thyroid®
- Publisher
- SAGE Publications
- Published
- 2019-10
- Volume
- 29
- Issue
- 10
- Pages
- 1465-1474
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2968986822
- Cited by
- 63
- References
- 54
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 15 · 2022: 10 · 2021: 10 · 2020: 6 · 2019: 4
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- green
- vbn.aau.dk
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Gentofte Hospital
- Novo Nordisk
- Rigshospitalet
- Lægeforeningen
- Novo Nordisk Fonden (NNF15OC0014622)
- Fonden til Lægevidenskabens Fremme
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- thyroid peroxidase antibodies, recurrent pregnancy loss, unexplained recurrent pregnancy loss, live birth rate, thyroid autoimmunity, thyroxine replacement, levothyroxine, immune tolerance, pregnancy outcome prediction, assisted reproduction, antithyroid drugs in pregnancy
- MeSH terms
- Abortion, Habitual, Adult, Autoantibodies, Female, Humans, Hypothyroidism, Iodide Peroxidase, Pregnancy, Risk Factors, Thyrotropin, Thyroxine, Autoimmunity, Logistic Models, Odds Ratio, Live Birth, Protective Factors
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