Serum metabolome indicators of early childhood development in the Brazilian National Survey on Child Nutrition (ENANI-2019)

Abstract Background The role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD). Methods Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children’s milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression was used to select metabolites with a variable importance projection ≥ 1. Results Twenty-eight top-ranked metabolites were included in linear regression models adjusted for child’s nutritional status, diet quality and age. Interaction between these metabolites and child age was tested. Cresol sulfate (β = −0.07; adjusted-p < 0.001), hippuric acid (β = −0.06; adjusted-p < 0.001), phenylacetylglutamine (β = −0.06; adjusted-p < 0.001), and trimethylamine- N -oxide (β = −0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged −1 SD: β = −0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (−1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03). Conclusion Serum biomarkers, including dietary and microbial derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays. Funding Supported by the Brazilian Ministry of Health and Brazilian National Research Council.