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

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 Liquid Chromatography-Mass Spectrometry. Subpopulations of T and B cells were measured using flow cytometry at birth, 48 h, one, four, and 12 months. Random forest analysis was used to link the metabolomics data with the T and B cell sub populations as well as infant and maternal characteristics.

Results: Modest associations (Q2 = 0.2-0.3) were found between the placental metabolome and kappa-deleting recombination excision circles (KREC) at birth and naïve B cells and memory T cells at 12 months. 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.

Conclusion: Our results indicate that metabolomic measurements of the placenta may not effectively recognize metabolites important for immune maturation.