Gestational diabetes & diabetes in pregnancy
Association and mediation pathways of maternal hyperglycaemia and liability to gestational diabetes with neonatal outcomes: A two‐sample Mendelian randomization study
Authors' conclusion
Maternal hyperglycemia is associated with higher birthweight (possibly indicating macrosomia), mediated via increased placental growth. GDM and T2D liability are related to preterm birth, whilst the association for T2D liability is driven by maternal adiposity.
Study context
- Population
- Summary statistics of European genome-wide association studies of offspring birthweight, gestational duration, spontaneous preterm and post-term birth (N = 131,279–210,248); instruments from GWAS of fasting glucose (FG), insulin sensitivity index (ISI), HbA1c, gestational diabetes mellitus (GDM) and T2D (N = 50,404–898,130)
- Comparison
- Genetically predicted maternal glycaemic traits (FG, ISI, HbA1c) and liability to GDM and T2D vs neonatal outcomes
- Outcome
- Offspring birthweight
Methodological detailsinverse-variance weighted method, multivariable Mendelian randomization (MR) adjusting for maternal body mass index (BMI), two-step MR mediation analysis
- Inverse-variance weighted method
- Multivariable MR adjusting for maternal BMI
- Two-step MR mediation analysis
Main finding
As reported in the abstract
FG and birthweight
SD per mmol/L 0.46
95% CI 0.32, 0.61
GDM liability and birthweight
SD per log odds 0.18
95% CI 0.08, 0.18
Proportion mediated by placental weight
32.8% to 77.7%
Further findings
- GDM liability and preterm birth, OR
- 1.07 (95% CI 1.01, 1.14)
- Higher HbA1c, GDM and T2D liability associated with preterm birth and shorter gestational duration; T2D association attenuated after adjustment for maternal BMI and gestational hypertension
Original publication
Association and mediation pathways of maternal hyperglycaemia and liability to gestational diabetes with neonatal outcomes: A two‐sample Mendelian randomization study. Diabetes Obes Metab. Published 6 November 2024. doi:10.
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