# A metabolomic signature of maternal BMI is associated with pregnancy complications across two independent pregnancy cohorts

## TL;DR

This study finds that specific blood metabolites linked to a mother's pre-pregnancy weight can predict pregnancy complications like diabetes and preeclampsia, suggesting potential for improved prenatal care.

## Contribution

The study identifies a metabolomic signature of maternal BMI that improves prediction of pregnancy complications beyond BMI alone.

## Key findings

- A BMI-associated metabolite score is strongly linked to gestational diabetes and preeclampsia.
- 16 metabolites mediate the effect of BMI on gestational diabetes.
- The metabolite model outperforms BMI alone in predicting outcomes in both early and late gestation.

## Abstract

Maternal obesity is increasingly common and linked to pregnancy complications, likely driven by underlying metabolic perturbations. This study investigates the association between maternal pre-pregnancy body mass index (BMI) and pregnancy complications through blood metabolomics, aiming to identify specific metabolites mediating these associations.

Data from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) and Vitamin D Antenatal Asthma Reduction Trial (VDAART) cohorts were used, with untargeted blood metabolomics performed on blood samples taken during early-, mid-, and late gestation. Associations were assessed using multivariable logistic regression and mediation analyses to explore metabolite pathways linking maternal BMI with pregnancy complications.

In the COPSAC2010 cohort, maternal pre-pregnancy BMI is associated with gestational diabetes (OR 1.90 [1.29-2.74], p = 6.75×10⁻⁴), caesarean section (OR 1.23 [1.03-1.47], p = 0.023), and birth induction (OR 1.42 [1.21-1.67], p = 2.86×10⁻⁵). A BMI-associated metabolite score is even more strongly associated with these complications and is independently associated with preeclampsia (OR 1.54 [1.04-2.26], p = 0.030). Validation in the VDAART cohort confirms the predictive value of the metabolite score for gestational diabetes (OR 2.10 [1.48-3.03], p = 4.97×10⁻⁵) and preeclampsia (OR 2.12 [1.32-3.47], p = 0.002), particularly in late gestation. Mediation analysis in COPSAC2010 identifies 16 metabolites as mediating the effect of BMI on gestational diabetes. A model based on this subset of metabolites significantly outperforms the full maternal BMI model in predicting outcomes during both early (p = 0.009) and late gestation (p = 0.016) in the VDAART cohort.

These findings suggest that integrating metabolomic profiling into prenatal care could improve the prediction and management of adverse pregnancy outcomes.

Many women enter pregnancy with a higher body weight, which increases the risk of complications such as diabetes, preeclampsia, and delivery by caesarean section. We wanted to understand why these risks occur and whether changes in the body’s metabolism could explain them. To investigate this, we studied blood samples from two large groups of pregnant women in Denmark and the United States. We measured hundreds of small molecules, known as metabolites, and looked at how they relate to body weight and pregnancy outcomes. We found that certain metabolites help explain the link between higher body weight and complications such as diabetes and preeclampsia. These results suggest that blood metabolite testing could one day improve pregnancy care by identifying women at higher risk early on.

Horner et al. derive a metabolomic signature of maternal pre-pregnancy BMI using longitudinal blood profiling from two pregnancy cohorts to investigate its link with pregnancy complications. They identify BMI-related metabolic pathways that mediate obesity-related risk, improving prediction of gestational diabetes and preeclampsia beyond BMI alone.