November 18, 2009 — 根據發表於11月17日線上第一版BMJ巢式案例控制研究的分析與一篇人口基礎研究，懷孕期間發生子癲前症的婦女，比其他婦女更可能在懷孕後期或之後發生甲狀腺功能低下。
Eunice Kennedy Shriver國立兒童健康與人類發展研究中心(NICHD)執行主任Susan B. Shurin醫師在新聞稿中表示，這些發現認為，有子癲前症病史者有可能發生甲狀腺功能低下。甲狀腺功能低下不難診斷，治療也不昂貴；替代治療可顯著改善病患的生活品質。
【兩篇研究】
這項分析的目標是評估懷孕期間和懷孕後，子癲前症和甲狀腺功能降低之間的關聯，使用懷孕期間巢狀案例研究 (1992-1995年間、未曾生育過之健康美國婦女的子癲前症鈣療預防計畫)的資料。納入分析的第二篇研究，是1995-1997年間以挪威人口為基礎的「Nord-Trondelag Health Study (HUNT-2)」研究，懷孕後進行追蹤，並與挪威的醫療生育登記連結。
November 18, 2009 — Women in whom preeclampsia develops during pregnancy are more likely than other women to have hypothyroidism in late pregnancy or subsequently, according to an analysis of a nested case-control study and a population-based study reported in the November 17 Online First issue of the BMJ.
"The findings suggest that the possible development of hypothyroidism is a consideration in patients with a history of preeclampsia," Susan B. Shurin, MD, acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), said in a news release. "Reduced thyroid functioning is easy to diagnose when suspected, and inexpensive to treat. Replacement therapy substantially improves quality of life of affected persons."
Two Studies
The goal of this analysis was to evaluate the association of preeclampsia with reduced thyroid function during and after pregnancy, with use of data from a nested case-control study during pregnancy (the Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous US women during 1992-1995). The second study included in this analysis, the Nord-Trondelag Health Study (HUNT-2), was a Norwegian population-based study during 1995-1997, with follow-up after pregnancy and linkage to the medical birth registry of Norway.
Study subjects were 141 women in the Calcium for Pre-eclampsia Prevention trial who had serum measurements of thyroid function before 21 weeks of gestation (baseline) and after onset of preeclampsia (before delivery), 141 normotensive control subjects with serum measurements at similar gestational ages, and 7121 women in the HUNT-2 who first delivered in 1967 or later and who had subsequent measurement of thyroid-stimulating hormone serum levels.
Study Endpoints
Primary study endpoints in the Calcium for Pre-eclampsia Prevention cohort were thyroid function tests, human chorionic gonadotropin levels, and levels of the antiangiogenic factor soluble fms-like tyrosine kinase 1. Primary study endpoints from HUNT-2 were odds ratios (ORs) for levels of thyroid-stimulating hormone above the reference range, according to preeclampsia status in singleton pregnancies before enrollment.
Thyroid-Stimulating Hormone Levels Increased
After the onset of preeclampsia, thyroid-stimulating hormone levels in predelivery specimens increased 2.42 times above baseline in patients from the Calcium for Pre-eclampsia Prevention cohort vs a 1.48 times increase in control subjects. For case patients vs control subjects, the ratio of the predelivery-to-baseline ratio was 1.64 (95% confidence interval [CI], 1.29 - 2.08). Compared with the control subjects, the women with preeclampsia had a greater decrease in free triiodothyronine levels (case-to-control ratio, 0.96; 95% CI, 0.92 - 0.99).
In women with preeclampsia, predelivery specimens, but not baseline specimens, were significantly more likely than control specimens to have concentrations of thyroid-stimulating hormone above the reference range (adjusted OR, 2.2; 95% CI, 1.1 - 4.4). The increase in thyroid-stimulating hormone concentration from baseline to predelivery was strongly associated with increasing quartiles of predelivery soluble fms-like tyrosine kinase levels, both in women in whom preeclampsia developed (P for trend = .002) and in normotensive control subjects (P for trend < .001).
In HUNT-2, women who had preeclampsia during their first pregnancy were more likely than other women to have thyroid-stimulating hormone levels greater than the reference range (> 3.5 mIU/l). Adjusted OR was 1.7 (95% CI, 1.1 - 2.5). This finding most likely reflected hypothyroid function in the absence of an autoimmune process because women with preeclampsia were more likely to have high concentrations of thyroid-stimulating hormone without thyroid peroxidase antibodies (adjusted OR, 2.6; 95% CI, 1.3 - 5.0). In women with preeclampsia in both their first and second pregnancies, this association was especially strong (OR, 5.8; 95% CI, 1.3 - 25.5).
"Many of these women still had reduced thyroid function [more than 20 years after their first pregnancies]," said lead author Richard J. Levine, MD, MPH, from NICHD's Division of Epidemiology, Statistics, and Prevention Research in Bethesda, Maryland, said in a news release. "This suggests that a history of preeclampsia may predispose women to the later development of reduced thyroid function."
Limitations of these studies include those inherent in observational studies and lack of follow-up beyond delivery in the Calcium for Pre-eclampsia Prevention trial.
"Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy," the study authors write.
The NICHD and the National Heart, Lung, and Blood Institute (NHLBI), both of the National Institutes of Health, supported this study. The Calcium for Pre-eclampsia Prevention trial was supported by NICHD and NHLBI. This substudy of the HUNT-2 was supported by the Norwegian University of Science and Technology and by the Central Norway Regional Health Authority.
One of the study authors (Dr. Karumanchi) has disclosed various financial relationships with the Burroughs Wellcome Fund, the Howard Hughes Medical Institute, the American Heart Association, Abbott, Beckman, Coulter, Roche, Johnson & Johnson, and Beth Israel Deaconess Medical Center for the use of angiogenesis-related proteins for the diagnosis and treatment of preeclampsia.
