Associations Between the Maternal Blood Microbiome During Pregnancy and Early Childhood Growth Trajectories: A Pilot Study

Objective: Maternal blood microbiome signatures during pregnancy have been linked to adverse birth outcomes. We conducted a pilot study to examine whether they are also associated with early childhood growth in offspring and to explore maternal metabolites as potential mediators of these relationships. Methods: This study included 50 mother-child dyads from a prospective pregnancy cohort. Children were selected based on distinct body mass index (BMI) growth trajectories from birth to 4 years, including 25 children in a rising-high-BMI trajectory and 25 in a low-BMI trajectory. Maternal plasma collected during the second trimester underwent 16S rRNA gene sequencing for microbial profiling and an untargeted metabolomics analysis. Microbial diversity indices were compared between groups. Multivariable logistic regression models assessed associations between microbial taxa and BMI trajectories with adjustment for covariates. Mediation analyses evaluated whether maternal metabolites mediated observed associations. Results: Higher maternal blood microbial α-diversity was observed among mothers of children in the rising-high-BMI trajectory. Greater abundance of Gammaproteobacteria/Proteobacteria (class/phylum) was associated with lower odds of membership in the rising-high-BMI trajectory, whereas Bacteroidia/Bacteroidota and Actinobacteria/Actinobacteriota were associated with a greater risk. Mediation analyses identified several maternal metabolites that potentially linked prenatal microbial taxa to child growth outcomes. Key mediators included metabolites involved in benzoate metabolism (e.g., 4-vinylphenol sulfate for taxa Gammaproteobacteria/Proteobacteria), lipid metabolism (e.g., 1-linoleoyl-GPG (18:2) for Bacteroidia/Bacteroidota), glutathione metabolism (cysteinylglycine disulfide for Bacteroidia/Bacteroidota), branched-chain amino acid metabolism (3-hydroxy-2-ethylpropionate for Bacteroidia/Bacteroidota), histidine metabolism (imidazole propionate for Actinobacteria/Actinobacteriota), and TCA cycle (glutaconate for Actinobacteria/Actinobacteriota). These pathways are implicated in oxidative stress, adipocyte differentiation, insulin signaling, and energy metabolism, processes that are highly relevant to obesity development. Conclusion: Findings suggest that prenatal blood microbial signatures may influence early childhood growth through metabolic pathways related to obesity. These pilot study findings support further investigation into the role of prenatal blood microbial signatures in child development and health outcome prediction in larger studies.