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A barrier in the children’s environmental health field has been the lack of early-warning systems to identify risks of childhood illness and developmental disorders. We aimed to develop a methodology to identify an accessible biomarker measured in a small amount of blood to distinguish newborns at elevated risk from a toxic prenatal exposure, using air pollutants as a case study. Because air pollutants are associated with altered DNA methylation, we developed a pipeline using DNA methylation signatures measured in umbilical cord blood, which could be used as predictors of prenatal exposure. We used air pollution indicators, including modelled trimester-specific and pregnancy average NO₂ and PM_2.5, and DNA methylation signatures from Illumina arrays measured in two New York City-based longitudinal birth cohorts from the Columbia Centre for Children’s Environmental Health. We developed a screening …