Infant microbes and metabolites point to childhood neurodevelopmental disorders

This study has followed a birth cohort for over twenty years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, HLA genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention deficit hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis, as well as early-emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.

Methods
For this investigation, we analyzed the earliest questionnaires derived from parents of ABIS children at one, three, and five years of age. The latest diagnoses considered in this investigation were obtained when the children were 21 to 23 years of age. All families provided informed consent to be included in this study. The ABIS study was approved by the Research Ethics Committee, Linköping University and Lund University, approval numbers Dnr 03-092; LiU 287.96, LU 83-97, LiU 321-99.and Linköping University Dnr 36287, Dnr 03-513, Dnr 2018/380-32.  In-depth methodology for the microbiome and metabolomic datasets is provided in our accompanying manuscript in Cell. (https://doi.org/10.1016/j.cell.2024.02.035)