Modification of the effects of prenatal manganese exposure on child neurodevelopment by maternal anemia and iron deficiency

Background: We evaluated: (1) associations of prenatal manganese (Mn) levels with child neurodevelopment at 4–6 years; (2) effect modification by maternal anemia and iron deficiency; and (3) sex-specific effects. Methods: We measured blood Mn, hemoglobin, and serum ferritin in mothers at the second trimester, third trimester, and at birth, and in cord blood from a prospective birth cohort in Mexico City (n = 571). McCarthy Scales of Children’s Abilities were measured at 4–6 years. Using linear regression, we estimated associations between prenatal Mn and neurodevelopment, examined anemia and iron deficiency as effect modifiers, and analyzed associations by child sex. Results: No direct associations were observed between Mn, anemia, or iron deficiency and McCarthy Scales. Second trimester iron deficiency and third trimester anemia modified the effect of Mn on child neurodevelopment. For instance, second trimester Mn was positively associated child memory scores in mother’s with normal ferritin (1.85 (0.02, 3.45)), but negatively associated in mother’s with low ferritin (−2.41 (−5.28, 0.47), interaction P value = 0.01), a pattern observed across scales. No effect modification at birth or in cord blood was observed. Conclusions: Anemia/iron deficiency during pregnancy may modify Mn impacts on child neurodevelopment, particularly in boys.