Associations of Hypothyroxinemia With Risk of Preeclampsia–Eclampsia and Gestational Hypertension

OBJECTIVE: To investigate the association between hypothyroxinemia and the risk of preeclampsia–eclampsia and gestational hypertension. DESIGN: Historical cohort study. METHODS: The study included pregnant individuals who delivered live-born singletons and had at least one thyroid function assessment during pregnancy at a tertiary hospital. Hypothyroxinemia was defined as thyroid-stimulating hormone (TSH) levels within the normal reference range and free thyroxine (FT4) levels lower than the tenth percentile. Risk ratios (RRs) with 95% confidence intervals (95% CIs) for preeclampsia–eclampsia and gestational hypertension between women with and without a diagnosis of hypothyroxinemia during pregnancy were estimated using a generalized estimating equation model. RESULTS: A total of 59,463 women with live-born singletons were included in the analysis. Logistic regression models with restricted cubic spline suggested that there was a U-shaped association between FT4 levels and preeclampsia–eclampsia risk. Compared with euthyroid women, those with hypothyroxinemia had an increased risk of preeclampsia–eclampsia (RR = 1.16, 95% CI: 1.02–1.31), and the risk increased with the increasing severity of hypothyroxinemia (p for trend < 0.001). Moreover, persistent hypothyroxinemia from the first to second trimesters was associated with an increased risk of preeclampsia–eclampsia (RR = 1.37, 95% CI: 1.03–1.83), especially for women with severe hypothyroxinemia (RR = 1.70, 95% CI: 1.12–2.58). In contrast, there was no association between hypothyroxinemia and gestational hypertension. CONCLUSION: Our study suggested that hypothyroxinemia was only associated with an increased risk of preeclampsia–eclampsia, especially in women with persistent hypothyroxinemia in the first half of pregnancy. Analyses of the associated risk of gestational hypertension with hypothyroxinemia were not significant.