Birth season shapes the infant metabolome and development in Tanzania: a secondary explorative analysis of the early life interventions for childhood growth and development in Tanzania (ELICIT) trial.

Rural communities in resource-limited settings are exposed to seasonal patterns in food insecurity. The pre- and early post-natal period is a key developmental window, sensitive to nutritional availability and quality. While season of birth has been associated with differences in epigenetic, developmental and health outcomes, it is unclear if this imprints on the developing metabolome and contributes to adverse phenotypic outcomes. Here we show that urinary and plasma metabolites in Tanzanian infants follow seasonal waveforms dependent upon their month of birth, persisting up to at least 18 months of life, which were related to food insecurity, breastmilk composition and rainfall. This includes developmentally relevant metabolites, including choline, trimethylamine-N-oxide, and polyunsaturated fatty acids. Cognitive measures at 18 months also followed seasonal waveforms based upon month of birth which correlated with seasonal metabolites. Additionally, variation in metabolic status modulated the effectiveness of a maternal-infant nicotinamide intervention targeting stunting. Our findings show that seasonal environmental pressures shape mother-infant dyad food insecurity with lasting ramifications for the infant metabolome and development. These findings support the need for season-dependent nutritional and lifestyle interventions targeting developmental shortfalls in these communities.