Thyroid function and hypertensive disorders of pregnancy: Insights from a sex-specific cohort study, Mendelian randomization, and experimental validation.
Aug 2026· International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics· 0 citations· 35 references
Medicine
TL;DR
An independent observational association between hyperthyroidism and an increased risk of HDP is demonstrated, and supportive genetic evidence for a possible bidirectional association between genetically predicted TSH and HDP is provided.
Abstract
Objective
To investigate the association of a history of hypertensive disorders of pregnancy (HDP) and a higher risk of cardiovascular disease using a sex-specific cohort study, bidirectional two-sample Mendelian randomization (MR), and in vitro experiments.
Methods
Multivariable logistic regression was used to assess the association between thyroid function and HDP. We performed bidirectional two-sample MR using summary statistics from genome-wide association study meta-analyses, FinnGen, and UKB to assess the potential association between thyroid function and HDP. In vitro experiments were conducted to explore the potential biologic mechanisms underlying the observed association.
Results
In the cohort (n = 119 668), hyperthyroidism was associated with higher HDP risk (odds ratio [OR] 1.79, 95% confidfence interval [CI] 1.10-2.92, P = 0.020; fully adjusted for confounders). MR identified a potential association of genetically predicted thyroid-stimulating hormone (TSH) on HDP (OR 0.92, 95% CI 0.85-0.99, P = 0.018), but no evidence was found to support a causal effect of hypothyroidism, hyperthyroidism, or free thyroxine on HDP. Reverse MR indicated that genetically predicted pre-eclampsia was associated with elevated TSH levels (β 0.12, 95% CI 0.05-0.19, P < 0.001). In vitro experiments confirmed and provided supportive mechanistic evidence that TSH may directly induce vascular endothelial injury and dysfunction.
Conclusion
This study demonstrates an independent observational association between hyperthyroidism and an increased risk of HDP, and provides supportive genetic evidence for a possible bidirectional association between genetically predicted TSH and HDP. These findings highlight TSH as a potential biomarker for HDP risk stratification.
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Jiahuan Luo, Ruopeng Zhang, Mengjie Song et al.· Medicine· 1 citation
Background Hypertensive disorders of pregnancy (HDP), including preeclampsia, gestational hypertension, and eclampsia, are common pregnancy complications that may have long-term consequences for offspring health. Emerging evidence suggests a potential link between maternal hypertension and childhood asthma, though findings remain inconsistent. This systematic review and meta-analysis aimed to synthesize the existing evidence on the association between HDP and asthma risk in offspring. Methods A comprehensive search of PubMed, Scopus, Web of Science, and EMBASE was conducted from database inception to 3 December 2024, restricted to peer-reviewed published studies. The eligibility criteria followed the PICOS framework. Observational studies (cohort, case–control, cross-sectional) assessing the association between HDP and asthma in offspring were included. Effect measures were converted to odds ratios (OR) with 95% confidence intervals (CI), and a meta-analysis was performed using random- and fixed-effects models. Heterogeneity was assessed jointly with Cochran’s Q test (p < 0.10) and the I2 statistic, and publication bias was examined through funnel plots and Egger’s test. Results Twenty studies encompassing over three million mother–infant pairs were included. The pooled OR for asthma risk in offspring of mothers with HDP was 1.14 (95% CI: 1.07–1.21), indicating a significant association. Subgroup analyses revealed a positive association with both preeclampsia (OR: 1.20; 95% CI: 1.12–1.28) and gestational hypertension (OR: 1.18; 95% CI: 1.02–1.36). Heterogeneity was high in some subgroups, such as gestational hypertension (I2 = 92.6%; p < 0.0001), suggesting variability across studies. As a secondary outcome, the association between HDP and wheezing in the offspring was assessed. The pooled OR was 1.07 (95% CI: 0.99–1.17), not reaching statistical significance, although positive trends were observed in some subtypes. Conclusion Maternal HDP is associated with an approximately 14–20% increased risk of asthma in offspring, highlighting the need for targeted early-life monitoring and intervention strategies. Further research is warranted to elucidate underlying mechanisms and optimize maternal–fetal health outcomes. Systematic review registration IS: CRD420251000229.
Nancy D. Calzada, Carlos A. Barba, Carlos Quispe-Vicuña et al.· Frontiers in Medicine· 0 citations
Background
Few studies have investigated the association between cardiovascular health (CVH) and thyroid dysfunction, and the modifying role of depression or anxiety remains unclear.
Methods
This longitudinal study included 360,332 UK Biobank participants without thyroid disease at baseline and with complete CVH scores. We examined the associations between CVH and the risks of hyperthyroidism and hypothyroidism using Cox proportional hazards regression models, quantified the relative contributions of CVH components using weighted quantile sum regression, and evaluated the mediating role of inflammatory markers. Furthermore, we investigated the modifying effects of depression and anxiety on these associations. A multi-state model was used to explore disease trajectories.
Results
During a median follow-up of 12.53 years, 1,533 and 7,542 participants developed hyperthyroidism and hypothyroidism, respectively. After multivariable adjustment, each 5-point increase in CVH score was associated with a 7% (95% confidence interval [CI], 4% to 9%) lower risk of hyperthyroidism and an 8% (95% CI, 7% to 9%) lower risk of hypothyroidism. A high CVH score was associated with a 50% (95% CI, 37% to 60%) lower risk of hyperthyroidism and a 45% (95% CI, 38% to 50%) lower risk of hypothyroidism. Among the CVH components, obesity and tobacco exposure contributed most to disease risk. Inflammatory markers partially mediated these associations. Depression and anxiety modified the association between CVH and hypothyroidism, and CVH showed a protective effect across the disease trajectories.
Conclusion
Maintaining favorable CVH was associated with a lower risk of thyroid dysfunction, particularly among individuals with good mental health.
Jilong Bai, Rui Ren, Panting Wei et al.· Endocrinology and Metabolism· 0 citations
Genetic evidence of potential associations between antidepressant use and increased risks of Hashimoto's thyroiditis and hypothyroidism is provided, and support consideration of thyroidfunction monitoring in patients receiving antidepressant treatment, particularly those with pre-existing thyroid risk factors.
Yingxian Ling, Qisong Chen· Actas espanolas de psiquiatr...· 0 citations
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Jiawei Shi, Weijie Jiang, Hui Chen et al.· Frontiers in Endocrinology· 0 citations
This MR study supported diabetes liability and higher alcohol intake as causal risk factors for DD, whereas genetically proxied obesity and smoking traits showed no clear causal effects, suggesting that better glycemic management and lower alcohol exposure may help reduce the risk of DD.
Heng Tian, Ling Hong, Wenlai Guo et al.· Korean Journal of Family Med...· 0 citations
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