This article was published in the BMJ today.
The whole article can be found at http://www.bmj.com/cgi/content/full/339/nov17_1/b4336Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study
Richard J Levine, senior investigator1, Lars J Vatten, professor2, Gary L Horowitz, associate professor3, Cong Qian, statistician4, Pal R Romundstad, associate professor2, Kai F Yu, senior statistician1, Anthony N Hollenberg, associate professor5, Alf I Hellevik, medical student2, Bjorn O Asvold, postdoctoral fellow2, S Ananth Karumanchi, associate professor5,6,7
1 Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Epidemiology, Statistics, and Prevention Research, Bethesda, MD 20892, USA, 2 Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway, 3 Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA, 4 Glotech, Rockville, MD, USA, 5 Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA, 6 Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA, 7 Howard Hughes Medical Institute, Boston, MA, USA
Correspondence to: R J Levine LevineRJ@mail.nih.gov
or S A Karumanchi email@example.com
To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy.
Design Nested case-control study during pregnancy and population based follow-up study after pregnancy. Setting
Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous women in the United States during 1992-5, and a Norwegian population based study (Nord-Trondelag Health Study or HUNT-2) during 1995-7 with linkage to the medical birth registry of Norway. Participants
All 141 women (cases) in the Calcium for Pre-eclampsia Prevention trial with serum measurements before 21 weeks’ gestation (baseline) and after onset of pre-eclampsia (before delivery), 141 normotensive controls with serum measurements at similar gestational ages, and 7121 women in the Nord-Trondelag Health Study whose first birth had occurred in 1967 or later and in whom serum levels of thyroid stimulating hormone had been subsequently measured.
Main outcome measures Thyroid function tests and human chorionic gonadotrophin and soluble fms-like tyrosine kinase 1 concentrations in the Calcium for Pre-eclampsia Prevention cohort and odds ratios for levels of thyroid stimulating hormone above the reference range, according to pre-eclampsia status in singleton pregnancies before the Nord-Trondelag Health Study. Results
In predelivery specimens of the Calcium for Pre-eclampsia Prevention cohort after the onset of pre-eclampsia, thyroid stimulating hormone levels increased 2.42 times above baseline compared with a 1.48 times increase in controls. The ratio of the predelivery to baseline ratio of cases to that of the controls was 1.64 (95% confidence interval 1.29 to 2.08). Free triiodothyronine decreased more in the women with pre-eclampsia than in the controls (case ratio to control ratio 0.96, 95% confidence interval 0.92 to 0.99). The predelivery specimens but not baseline samples from women with pre-eclampsia were significantly more likely than those from controls to have concentrations of thyroid stimulating hormone above the reference range (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4). Both in women who developed pre-eclampsia and in normotensive controls the increase in thyroid stimulating hormone concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1 (P for trend 0.002 and <0.001, respectively). In the Nord-Trondelag Health Study, women with a history of pre-eclampsia in their first pregnancy were more likely than other women (adjusted odds ratio 1.7, 95% confidence interval 1.1 to 2.5) to have concentrations of thyroid stimulating hormone above the reference range (>3.5 mIU/l). In particular, they were more likely to have high concentrations of thyroid stimulating hormone without thyroid peroxidase antibodies (adjusted odds ratio 2.6, 95% confidence interval 1.3 to 5.0), suggesting hypothyroid function in the absence of an autoimmune process. This association was especially strong (5.8, 1.3 to 25.5) if pre-eclampsia had occurred in both the first and the second pregnancies. Conclusion
Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later years.