Association and mediation pathways of maternal hyperglycaemia and liability to gestational diabetes with neonatal outcomes: A two‐sample Mendelian randomization study

Nov 6, 2024Diabetes, obesity & metabolism

How high blood sugar and risk of gestational diabetes in mothers relate to newborn health outcomes

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Fasting glucose levels increase birthweight by 0.46 SD per mmol/L, mediated by placental weight.

Gestational diabetes mellitus (GDM) liability is associated with higher birthweight at 0.18 SD per log odds.
Higher levels of glycated hemoglobin (HbA1c), GDM, and type 2 diabetes (T2D) liability correlate with an increased risk of preterm birth.
The proportion of the association between maternal hyperglycemia and birthweight mediated by placental weight ranges from 32.8% to 77.7%.
The relationship between T2D liability and preterm birth is influenced by maternal body mass index and gestational hypertension.

AI simplified

AIMS: Maternal hyperglycemia is linked to adverse neonatal outcomes. However, current evidence was insufficient for mechanistic pathways. We aim to use two-sample Mendelian randomization (MR) to obtain a comprehensive understanding of the causal association and mediation pathways.

MATERIALS AND METHODS: Genetic variants of fasting glucose (FG), insulin sensitivity index (ISI), glycated haemoglobin (HbA1c), gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) were used as instruments (N = 50 404-898 130). The associations with offspring birthweight, gestational duration, spontaneous preterm and post-term birth were assessed by the inverse-variance weighted method, using summary statistics of European genome-wide association studies (N = 131 279-210 248). Sensitivity analyses, including multivariable MR removing pleiotropic effect from maternal body mass index (BMI), assessed the robustness. Mediation via placental weight and maternal hypertension were assessed via a two-step MR design.

RESULTS: FG (0.46 SD per mmol/L, 95% confidence interval [95% CI]: 0.32, 0.61) and GDM liability (0.18 SD per log odds, 95% CI: 0.08, 0.18) were positively associated with birthweight, with consistent findings for HbA1c, T2D liability and ISI. These associations were mediated by placental weight (proportion mediated: 32.8% to 77.7%). Higher HbA1c, GDM and T2D liability were associated with preterm birth (odds ratios for GDM: 1.07, 95% CI: 1.01, 1.14) and shorter gestational duration, whilst the association for T2D attenuated after adjusted for maternal BMI and gestational hypertension.

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.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (XML) ↗View full text ↗

Association and mediation pathways of maternal hyperglycaemia and liability to gestational diabetes with neonatal outcomes: A two‐sample Mendelian randomization study

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief