Maternal Subclinical Hypothyroidism Associated With Higher Risk of Pre-Eclampsia

Investigators assessed the impact of maternal thyroid dysfunction on hypertensive disorders of pregnancy, such as gestational hypertension and pre-eclampsia.

Compared with euthyroidism, maternal subclinical hypothyroidism has been found to be associated with increased risk for pre-eclampsia, according to the results of a study published in The Lancet Diabetes & Endocrinology.

Researchers conducted a systematic literature review and meta-analysis to assess the relationship between abnormalities in thyroid function tests and the risk of gestational hypertension and pre-eclampsia. They searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from inception to December 27, 2019, for relevant studies.

The primary study outcomes were documented gestational hypertension and pre-eclampsia as separate entities.

A total of 1539 published studies were identified, from which 19 cohorts were included in the analysis after the authors agreed to participate. The final study population included 46,528 women with a mean maternal age of 29.1 years (SD, 5.2); 39,826 (85.6%) women had sufficient data on thyroid-stimulating hormone (TSH) concentration, free thyroxine (FT₄) concentration, and thyroid peroxidase antibody status to be classified according to their thyroid function status. Among this group, 1275 participants (3.2%) had subclinical hypothyroidism, 933 (2.3%) had isolated hypothyroxinemia, 619 (1.6%) had subclinical hyperthyroidism, and 337 (0.8%) had overt hyperthyroidism.

Subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (3.6% vs 2.1%; odds ratio [OR] 1.53; 95% CI, 1.09-2.15) but not with gestational hypertension (5.7% vs 4.2%; OR 1.18; 95% CI, 0.91-1.53) compared with euthyroidism.

Subclinical hyperthyroidism and isolated hypothyroxinemia were not associated with gestational hypertension or pre-eclampsia. Compared with thyroid peroxidase antibody negativity, no association was found between thyroid peroxidase antibody positivity and gestational hypertension or pre-eclampsia.

When TSH and FT₄ were analyzed as continuous variables, a U-shaped association was observed between TSH and pre-eclampsia (P =.0001) and between TSH and the composite outcome (P <.0001). No association was found with FT₄ for any of the outcomes.

Study limitations include the observational design and the inability to include all of the published cohorts in the analysis. The researchers were also unable to include personal or familial history of hypertensive gestational disorders as part of their exclusion criteria or assess the differential risk of common subcategories of hypertensive disorders of pregnancy based on gestational age at the time of onset.

“These findings add to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy and indirectly inform the optimal TSH target for treatment in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies,” concluded the investigators.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Toloza FJK, Derakhshan A, Männistö T, et al. Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis. Lancet Diabetes Endocrinol. Published online March 4, 2022. doi:10.1016/S2213-8587(22)00007-9