# Pregestational Diabetes and Adverse Pregnancy Results: A Mendelian Randomization Study

## TL;DR

This study uses genetic data to investigate whether pre-pregnancy diabetes causes poor pregnancy outcomes like stillbirth and preterm birth.

## Contribution

The study applies Mendelian randomization to assess causality between pregestational diabetes and adverse pregnancy outcomes.

## Key findings

- No significant causal link was found between pregestational diabetes and stillbirth.
- Pregestational diabetes was not causally associated with miscarriage or preterm birth.
- Results showed no evidence of pleiotropy or heterogeneity in the analyzed outcomes.

## Abstract

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.

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.

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).

Our findings indicate that there is no direct causal link between PGDM and the likelihood of MIS, SB, and PTB.