Associations of the placental metabolome with immune maturation up to one year of age in the Swedish NICE-cohort

Abstract

Abstract Introduction: Allergies and other immune-mediated diseases are thought to result from incomplete maturation of the immune system early in life. We previously showed that infants’ metabolites at birth were associated with immune cell subtypes during infancy. The placenta supplies the fetus with nutrients but may also provide immune maturation signals. Objectives: To examine the relationship between metabolites in placental villous tissue and immune maturation during the first year of life and infant and maternal characteristics (gestational length, birth weight, sex, parity, maternal age, and BMI). Methods: Untargeted metabolomics was measured using a Liquid Chromatography-Mass Spectrophotometer and subpopulations of T and B cells using flow cytometry at birth, 48 hours, one, four, and 12 months. Random forest modeling showed modest associations (Q2 = 0.2–0.3) between the placental metabolome and kappa-deleting recombination excision circles (KREC) at birth and naïve B cells and memory T cells at 12 months. Results: Weak associations were observed between the placental metabolome and sex and parity. Still, most metabolite features of interest were of low intensity compared to associations previously found in cord blood, suggesting that underlying metabolites were not of placental origin. Conclusions: Our results indicate that metabolomic measurements of the placenta may not effectively recognize metabolites important for immune maturation.