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- Original article Impaired pulmonary function mediates the impact of preterm birth on later-life stroke: a 2-step, multivariable Mendelian randomization study
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Xingzhi Guo
, Peng Tang
, Chen Hou
, Yue Liu
, Rui Li
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Epidemiol Health 2023;e2023031
DOI: https://doi.org/10.4178/epih.e2023031 [Accepted]
Published online: March 3, 2023
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Corresponding author:
Rui Li,
Email: rli@nwpu.edu.cn
Abstract
Objectives
Observational studies have suggested an association between preterm birth and stroke in late adulthood, but it remains unclear whether the association is causal. The purpose of this study was to evaluate the causal effects of gestational age on stroke and to determine the pathophysiological mechanisms underlying the causal associations.
Methods
Two-sample Mendelian randomization (MR) was performed to assess the causal effects of fetal gestational duration, early preterm birth (EPB), preterm birth, or postterm birth on stroke and its subtypes. Two-step MR and multivariable MR (MVMR) were additionally used to determine the role of common stroke risk factors, including cardiovascular diseases, hypertension, pulmonary impairment, inflammation, and metabolic diseases, in mediating the causal associations between gestational age and stroke and its subtypes.
Results
Genetically predicted EPB increased the risk of cardioembolic stroke (CES) (odds ratio [OR]=1.115; 95% CI, 1.036-1.200; P=0.004) and large artery stroke (LAS) (OR=1.131; 95% CI, 1.031-1.241; P=0.009). The TSMR results showed that EPB was associated with a lower forced expiratory volume in the first second and forced vital capacity ratio (FEV1/FVC) (β=-0.020; 95% CI, -0.035 to -0.005; P=0.009), which increased the risk of CES and LAS. Further MVMR analysis showed that the associations between EPB and stroke disappeared after adjustment for FEV1/FVC.
Conclusions
Our data demonstrate that EPB is causally associated with an elevated risk of CES and LAS, and that pulmonary dysfunction mediates the causal impact of EPB on CES and LAS.
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