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Xingzhi Guo 1 Article
Impaired pulmonary function mediates the impact of preterm birth on later-life stroke: a 2-step, multivariable Mendelian randomization study
Xingzhi Guo, Peng Tang, Chen Hou, Yue Liu, Rui Li
Epidemiol Health. 2023;45:e2023031.   Published online March 3, 2023
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AbstractAbstract AbstractSummary PDFSupplementary Material
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.
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 Mendelian randomization (TSMR) and multivariable Mendelian randomization (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.
Genetically predicted EPB increased the risk of cardioembolic stroke (CES; odds ratio [OR], 1.115; 95% confidence interval [CI], 1.036 to 1.200; p=0.004) and large artery stroke (LAS; OR, 1.131; 95% CI, 1.031 to 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.
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.
Key Message
Genetically predicted early preterm birth (EPB) is significantly associated with an increased risk of cardioembolic stroke (CES) and large artery stroke (LAS). Further multivariable Mendelian randomization analysis demonstrates that pulmonary impairment mediates the causal impact of EPB on CES and LAS in adulthood.


Citations to this article as recorded by  
  • Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review
    Grace M. Power, Eleanor Sanderson, Panagiota Pagoni, Abigail Fraser, Tim Morris, Claire Prince, Timothy M. Frayling, Jon Heron, Tom G. Richardson, Rebecca Richmond, Jessica Tyrrell, Nicole Warrington, George Davey Smith, Laura D. Howe, Kate M. Tilling
    European Journal of Epidemiology.2024; 39(5): 501.     CrossRef
  • Causal associations of circulating Helicobacter pylori antibodies with stroke and the mediating role of inflammation
    Xingzhi Guo, Peng Tang, Xin Zhang, Rui Li
    Inflammation Research.2023; 72(6): 1193.     CrossRef

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