Pre-Eclampsia, Soluble Fms-Like Tyrosine Kinase 1, and the Risk of Reduced Thyroid Function: Nested Case-Control and Population Based Study
Year: 2010
Type: article
Study design: Observational Study
Abstract: This study investigated whether excess amounts of soluble fms-like tyrosine kinase 1 in patients with pre-eclampsia might be associated with reduced thyroid function during and after pregnancy. The first part of the study was a nested case-control study within the Calcium for Pre-eclampsia Prevention trial conducted between 1992 and 1995 in the United States. Thyroid function during pregnancy was compared in nulliparous singletons with pre-eclampsia (case group, n = 141) and without pre-eclampsia (normotensive control group, n = 141). The second part was a follow-up population-based study, the Nord-Trondelag Health Study (HUNT-2), that investigated whether pre-eclampsia in a previous pregnancy increased the risk of reduced thyroid function later in life. The HUNT-2 study participants were 7121 women who had delivered their first child during or after 1967. In the Calcium for Pre-eclampsia Prevention trial, after the onset of pre-eclampsia and before delivery, the increase in thyroid-stimulating hormone (TSH) concentrations from baseline levels was higher in the case than in the control group (2.48 vs. 1.48 times above baseline). Comparison of the TSH predelivery to baseline ratios in the cases and controls showed that the case ratio was 1.64 times higher (95% confidence interval [CI], 1.29–2.08). Significantly greater reductions occurred in levels of free triiodothyronine in women with pre-eclampsia compared to controls; the case ratio to control ratio was 0.96, with a 95% CI of 0.92–0.99. In predelivery but not baseline specimens, women with pre-eclampsia were significantly more likely than controls to have concentrations of TSH above the reference range (adjusted odds ratio [OR], 2.2; 95% CI, 1.1–4.4). The increase in TSH concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1, in both women who developed pre-eclampsia and in normotensive controls (P for trend <0.002 and <0.001, respectively). In the HUNT-2 study, the probability of having serum TSH concentrations greater than the clinical reference range (>3.5 mIU/L) was higher among women with a history of pre-eclampsia in their first pregnancy in comparison to those who did not develop pre-eclampsia in their first pregnancy (adjusted OR, 1.7; 95% CI, 1.1–2.5). The association of pre-eclampsia in the first pregnancy with high concentrations of TSH (>4.0 mIU/L) was more likely in the absence of thyroid peroxidase antibodies (adjusted OR, 2.6; 95% CI, 1.3–5.0). The association with hypothyroid function was particularly strong in women who had experienced pre-eclampsia in 2 pregnancies (adjusted OR, 5.8; 95% CI, 1.3–25.5). These findings suggest that increased serum concentration of soluble fms-like tyrosine kinase 1, especially after onset of pre-eclampsia, is associated with a greater subsequent risk of subclinical hypothyroidism during pregnancy and that a history of pre-eclampsia increases the risk of sub-clinical hypothyroidism in later years.
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1975054558