Abstract
BackgroundNo previous study has examined the effect of maternal hypothyroidism on a broad spectrum of cardiovascular disease (CVD) endpoints in the offspring.MethodsA 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.ResultsOffspring 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.ConclusionsMaternal 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.
Highlights
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide [1, 2]
We included all live singleton births born in Denmark from the 1st of January 1978 to the 31st of December 1998 identified from the Danish Medical Birth Register (DMBR) [14]
We further evaluated the risks according to the time of the first diagnosis of maternal hypothyroidism, i.e. before conception, during pregnancy, up to five years after delivery, and more than five years after delivery
Summary
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide [1, 2]. Sufficient expression of maternal thyroid hormones is crucial for foetal development [6]. Maternal hypothyroidism may affect the development of the foetal cardiovascular system [11, 12]. Human study has indicated an association between maternal hypothyroidism and congenital heart disease [12]. Study has suggested a programming effect of maternal thyroid function on blood pressure of offspring at the age of 20 years [13]. To our knowledge, no previous study has examined the effect of maternal hypothyroidism on a broad spectrum of CVD endpoints at elder ages. No previous study has examined the effect of maternal hypothyroidism on a broad spectrum of cardiovascular disease (CVD) endpoints in the offspring
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