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Background and objectives: A landmark longitudinal study, conducted in Costa Rica in the 1980s, found that children with chronic iron deficiency compared with good iron status in infancy had 8 to 9 points lower cognitive scores, up to 19 years of age. Our objective was to examine this association in a contemporary, high-resource setting. Methods: This was a prospective observational study of children aged 12 to 40 months screened with hemoglobin and serum ferritin. All parents received diet advice; children received oral iron according to iron status. After 4 months, children were grouped as: chronic iron deficiency (iron deficiency anemia at baseline or persistent nonanemic iron deficiency) or iron sufficiency (IS) (IS at baseline or resolved nonanemic iron deficiency). Outcomes measured at 4 and 12 months included the Early Learning Composite (from the Mullen Scales of Early Learning) and serum ferritin. Results: Of 1478 children screened, 116 were included (41 chronic, 75 sufficient). Using multivariable analyses, the mean between-group differences in the Early Learning Composite at 4 months was -6.4 points (95% confidence interval [CI]: -12.4 to -0.3, P = .04) and at 12 months was -7.4 points (95% CI: -14.0 to -0.8, P = .03). The mean between-group differences in serum ferritin at 4 months was 14.3 μg/L (95% CI: 1.3-27.4, P = .03) and was not significantly different at 12 months. Conclusions: Children with chronic iron deficiency, compared with children with IS, demonstrated improved iron status, but cognitive scores 6 to 7 points lower 4 and 12 months after intervention. Future research may examine outcomes of a screening strategy on the basis of early detection of iron deficiency using serum ferritin. [ABSTRACT FROM AUTHOR]