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Pregestational Diabetes and Adverse Pregnancy Results: A Mendelian Randomization Study Publisher Pubmed



Hantoushzadeh S1 ; Zakidizaji M2 ; Habibi D3 ; Sahebi L4 ; Saeidian AH5 ; Dashtkoohi M1 ; Saeedinia M6 ; Mirtavoosmahyar H7 ; Heidary Z1
Authors
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Authors Affiliations
  1. 1. Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
  3. 3. Department of Epidemiology and Biostatistics, School of Public Health, Babol University of Medical Sciences, Babol, Iran
  4. 4. Maternal, Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Surgery, Rasool-E Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Archives of Iranian medicine Published:2025


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. © 2025 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.