Objectives: Maternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the thyroid autoimmunity per se.
Methods: We performed a national and regional study in the Danish population. The national study was register-based, and the study population included all singleton pregnancies in Denmark from 1999-2015 (n=1,014,775). The regional study included the biochemical measurement of TSH, thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region Pregnancy Cohort which was established from 2011-2015 (n=14,573). Information on outcome of preeclampsia was obtained from hospital diagnoses in the Danish National Hospital Register. The associations between maternal thyroid function and thyroid autoimmunity and outcome of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders (e.g. maternal age, smoking, diabetes).
Results: In the nationwide study cohort, altogether 2.2% of pregnant women with no history of thyroid disease (reference group) were diagnosed with preeclampsia in the pregnancy. The prevalence of preeclampsia was 3.0% among pregnant women with hypothyroidism (aOR of 1.3 (95% CI: 1.2-1.4)) and 4.3% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.7 (95% CI: 1.3-2.1). In the regional cohort, altogether 2.4% of women with early pregnancy TSH in the range from 0.1-2.49 mIU/l (reference group) were diagnosed with preeclampsia in the pregnancy. The prevalence of preeclampsia was 3.2% among women with early pregnancy TSH in the range from 2.5 to 4.99 mIU/l (aOR 1.1 (95% CI: 0.8-1.5), and 6.4% among women with TSH at or above 5.0 mIU/l (aOR 2.3 (95% CI: 1.2-4.4)). Considering thyroid autoimmunity, preeclampsia was diagnosed in 2.2% of women who were positive for TPO-Ab (> 59 U/ml) and/or Tg-Ab (> 33 U/ml) in the early pregnancy with an aOR of 0.9 (95% CI: 0.6-1.2).
Conclusions: In two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia.
10 Sep 2022 - 13 Sep 2022