{"title":"Pregestational Diabetes and Adverse Pregnancy Results: A Mendelian Randomization Study.","authors":"Sedigheh Hantoushzadeh, Majid Zaki-Dizaji, Danial Habibi, Leyla Sahebi, Amir Hesam Saeidian, Mohadese Dashtkoohi, Mostafa Saeedinia, Hanifeh Mirtavoos-Mahyar, Zohreh Heidary","doi":"10.34172/aim.33461","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia in pregnancy is believed to be associated with negative pregnancy outcomes. However, establishing a causal connection between diabetes mellitus (DM) and adverse pregnancy results is challenging due to the limitations inherent in traditional observational studies.</p><p><strong>Methods: </strong>Our study used a two-sample Mendelian randomization (MR) technique to examine the possible influence of pregestational diabetes mellitus (PGDM) on adverse pregnancy outcomes. Summary-level data were obtained from genome-wide association studies (GWAS) of European ancestry and FinnGen biobank. The primary analysis employed the random-effects multiplicative inverse variance weighted (IVW) technique to appraise causal relationships between PGDM and adverse outcomes. Heterogeneity and pleiotropy were assessed using Cochran's Q statistic, Rucker's Q statistic, and the I² statistic. Sensitivity analyses were conducted using MR-Egger and weighted median methods. Additionally, outlier detection techniques, including MR-PRESSO and RadialMR, were applied.</p><p><strong>Results: </strong>The results from the IVW method indicated no significant causal association between PGDM and stillbirth (SB) (OR (SE)=0.99 (0.001); <i>P</i> value=0.992), miscarriage (MIS) (OR (SE)=0.97 (0.016); <i>P</i> value=0.125), and preterm birth (PTB) (OR (SE)=1.072 (0.028); <i>P</i> value=0.014). Pleiotropy and heterogeneity tests revealed no evidence of pleiotropy for SB, MIS, and PTB (MR-Egger intercept <i>P</i> value=0.296, 0.525, and 0.532, respectively), with no observed heterogeneity for SB, MIS, and PTB (Q- <i>P</i> values of IVW were 0.929, 0.999, and 0.069, and MR-Egger were 0.931, 0.999, and 0.065, respectively).</p><p><strong>Conclusion: </strong>Our findings indicate that there is no direct causal link between PGDM and the likelihood of MIS, SB, and PTB.</p>","PeriodicalId":55469,"journal":{"name":"Archives of Iranian Medicine","volume":"28 2","pages":"81-87"},"PeriodicalIF":1.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892093/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Iranian Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.34172/aim.33461","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Hyperglycemia in pregnancy is believed to be associated with negative pregnancy outcomes. However, establishing a causal connection between diabetes mellitus (DM) and adverse pregnancy results is challenging due to the limitations inherent in traditional observational studies.
Methods: Our study used a two-sample Mendelian randomization (MR) technique to examine the possible influence of pregestational diabetes mellitus (PGDM) on adverse pregnancy outcomes. Summary-level data were obtained from genome-wide association studies (GWAS) of European ancestry and FinnGen biobank. The primary analysis employed the random-effects multiplicative inverse variance weighted (IVW) technique to appraise causal relationships between PGDM and adverse outcomes. Heterogeneity and pleiotropy were assessed using Cochran's Q statistic, Rucker's Q statistic, and the I² statistic. Sensitivity analyses were conducted using MR-Egger and weighted median methods. Additionally, outlier detection techniques, including MR-PRESSO and RadialMR, were applied.
Results: The results from the IVW method indicated no significant causal association between PGDM and stillbirth (SB) (OR (SE)=0.99 (0.001); P value=0.992), miscarriage (MIS) (OR (SE)=0.97 (0.016); P value=0.125), and preterm birth (PTB) (OR (SE)=1.072 (0.028); P value=0.014). Pleiotropy and heterogeneity tests revealed no evidence of pleiotropy for SB, MIS, and PTB (MR-Egger intercept P value=0.296, 0.525, and 0.532, respectively), with no observed heterogeneity for SB, MIS, and PTB (Q- P values of IVW were 0.929, 0.999, and 0.069, and MR-Egger were 0.931, 0.999, and 0.065, respectively).
Conclusion: Our findings indicate that there is no direct causal link between PGDM and the likelihood of MIS, SB, and PTB.
期刊介绍:
Aim and Scope: The Archives of Iranian Medicine (AIM) is a monthly peer-reviewed multidisciplinary medical publication. The journal welcomes contributions particularly relevant to the Middle-East region and publishes biomedical experiences and clinical investigations on prevalent diseases in the region as well as analyses of factors that may modulate the incidence, course, and management of diseases and pertinent medical problems. Manuscripts with didactic orientation and subjects exclusively of local interest will not be considered for publication.The 2016 Impact Factor of "Archives of Iranian Medicine" is 1.20.