TY - JOUR
T1 - Association of Maternal Hypothyroidism With Cardiovascular Diseases in the Offspring
AU - Miao, Maohua
AU - Liu, Hui
AU - Yuan, Wei
AU - Madsen, Nicolas
AU - Yu, Yongfu
AU - László, Krisztina D.
AU - Liang, Hong
AU - Ji, Honglei
AU - Li, Jiong
N1 - Funding Information:
This work was supported by grants from the National Key Research and Development Program (2016YFC1000505, 2018YFC1002801); Independent Research Fund Denmark (DFF-6110-00019B, DFF-9039-000010B); the Lundbeck Foundation (R232-2016-2462 and R265-2017-4069); the Nordic Cancer Union(R275-A15770); the Karen Elise Jensens Fond (2016); Novo Nordisk Fonden (NNF18OC0052029), Innovation-oriented Science and Technology Grant from NHC Key Laboratory of Reproduction Regulation (CX2017-06), the National Nature Science Foundation of China (82073570), the Swedish Heart and Lung Foundation (20180306), the Karolinska Institutet’s Research Foundation (2018-01547), and the Swedish Council for Working Life and Social Research (2015-00837).
Publisher Copyright:
© Copyright © 2021 Miao, Liu, Yuan, Madsen, Yu, László, Liang, Ji and Li.
PY - 2021/8/31
Y1 - 2021/8/31
N2 - Background: No previous study has examined the effect of maternal hypothyroidism on a broad spectrum of cardiovascular disease (CVD) endpoints in the offspring. Methods: A nationwide population-based cohort study based on the linkage of several Danish nationwide registries was conducted to explore whether maternal hypothyroidism is associated with offspring’s CVD. Altogether 1,041,448 singletons born between the 1st of January 1978 and the 31st of December 1998 were investigated from the age of 8 years to the 31st of December 2016. Exposure was maternal diagnosis of hypothyroidism across lifespan and the outcome of interest was a CVD diagnosis in the offspring. Cox regression models were performed to estimate the hazard ratios (HRs) of CVD. Results: Offspring born to mothers with hypothyroidism had an increased risk of CVD (hazard ratios (HR)=1.23, 95% confidence interval (CI): 1.12-1.35), and of several subcategories of CVD including hypertension, arrhythmia, and acute myocardial infarction in offspring. The magnitude of association was the most pronounced in an exposure occur during pregnancy (HR=1.71, 95% CI: 1.10-2.67), which is consistent across all the subgroup analysis, including sibling analysis. Conclusions: Maternal hypothyroidism is associated with an increased risk of CVD in offspring. Thyroid hormone insufficiency during pregnancy may predominantly contribute to the observed associations; however, the effects of a shared genetic background and a time-stable familial environment/lifestyle factors cannot be excluded.
AB - Background: No previous study has examined the effect of maternal hypothyroidism on a broad spectrum of cardiovascular disease (CVD) endpoints in the offspring. Methods: A nationwide population-based cohort study based on the linkage of several Danish nationwide registries was conducted to explore whether maternal hypothyroidism is associated with offspring’s CVD. Altogether 1,041,448 singletons born between the 1st of January 1978 and the 31st of December 1998 were investigated from the age of 8 years to the 31st of December 2016. Exposure was maternal diagnosis of hypothyroidism across lifespan and the outcome of interest was a CVD diagnosis in the offspring. Cox regression models were performed to estimate the hazard ratios (HRs) of CVD. Results: Offspring born to mothers with hypothyroidism had an increased risk of CVD (hazard ratios (HR)=1.23, 95% confidence interval (CI): 1.12-1.35), and of several subcategories of CVD including hypertension, arrhythmia, and acute myocardial infarction in offspring. The magnitude of association was the most pronounced in an exposure occur during pregnancy (HR=1.71, 95% CI: 1.10-2.67), which is consistent across all the subgroup analysis, including sibling analysis. Conclusions: Maternal hypothyroidism is associated with an increased risk of CVD in offspring. Thyroid hormone insufficiency during pregnancy may predominantly contribute to the observed associations; however, the effects of a shared genetic background and a time-stable familial environment/lifestyle factors cannot be excluded.
KW - cardiovascular disease
KW - hypothyroidism
KW - in utero exposure
KW - nationwide cohort study
KW - register-based
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U2 - 10.3389/fendo.2021.739629
DO - 10.3389/fendo.2021.739629
M3 - Article
C2 - 34531830
AN - SCOPUS:85114869685
SN - 1664-2392
VL - 12
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 739629
ER -