Manganese and lead co-exposure and neurodevelopment β, MDI: excluding outliers, –1.39 (95% CI: –2.36, –0.41); total sample, –1.27 (95% CI: –2.18, –0.37); PDI: excluding outliers, –1.00 (95% CI: –1.90, –0.10) ; total sample, –0.92 (95% CI: –1.76, –0.09)]. We also conducted analyses excluding one participant who had very low MDI and PDI scores at 24 months (scores of 50 for both), and results were similar, with the exception of a weaker effect estimate for 24-month PDI [adjusted β, manganese quintile 5 × continuous lead: excluding par- ticipant, –1.01 (95% CI: –2.32, 0.30); total sample, –1.60 (95% CI: –2.93, –0.27)]. Discussion This study suggests that joint exposure to manganese and lead is associated with greater deficits in both mental and psychomotor Table 3. Interaction coefficients from regression modelsa of 12-month metals and five time points of Bayley scores [β-coefficient (95% CI)]. Manganese (quintile 1)b × leadc,d Manganese (quintile 5)e × leadc,d aAdjusted for sex, gestational age, hemoglobin, maternal IQ, and maternal education. Manganese and lead included as main effects. bRange, 15.30–20.16 μg/L. cBlood lead variable centered at mean: 5.09 μg/dL. dCompared with manganese quintiles 2–4. eRange, 28.14–73.95 μg/L. Mn quintiles 1–4 Mn quintile 5 n 275 272 273 260 250 275 271 273 260 250 –0.11 (–1.42, 1.20) –0.87 (–2.16, 0.42) 0.63 (–1.18, 2.44) –0.03 (–1.41, 1.35) 0.46 (–0.93, 1.84) 0.69 (–0.50, 1.89) –0.69 (–2.08, 0.71) –0.21 (–1.59, 1.18) 0.51 (–1.06, 2.07) –1.12 (–2.82, 0.58) –0.94 (–2.21, 0.33) –1.74 (–3.00, –0.49) –1.62 (–3.36, 0.12) –1.08 (–2.42, 0.26) –1.10 (–2.44, 0.24) 0.15 (–1.00, 1.31) –1.20 (–2.45, 0.05) –1.60 (–2.93, –0.27) –1.69 (–3.21, –0.17) –1.92 (–3.56, –0.28) 30 months, adjusted β = –1.69 (95% CI: –3.21, –0.17); 36 months, adjusted β = –1.92 (95% CI: –3.56, –0.28)]. Although individual interaction effect estimates appeared to become stronger over time, the three-way interaction term lead × highest quintile of manganese × time) in the mixed-effects model did not reach statistical significance [β = –0.31 (95% CI: –0.64, 0.02)]. At low blood manganese levels, we did not observe a manganese–lead interaction. Figure 2 shows increased sensitivity to adverse lead effects on 24-month PDI among children with blood manganese in quintile 5 versus quin- tiles 1–4 [lead × highest manganese quintile, adjusted β = –1.57 (95% CI: –2.89, –0.25)]. Twenty-four–month blood metals. As with mental development, we observed no significant interactions between 24-month manganese and lead on psychomotor devel- opment (Table 2). Sensitivity analyses. Crude estimates for 12-month manganese–lead interaction among all children, including those missing covariate data, were weaker than those for study partici- pants with complete data but still suggest lower neurodevelopment scores with coexposure [e.g., crude β for interaction between manganese quintile 5 × continuous lead, 18-month MDI: all children, –0.96 (95% CI: –1.86, –0.06); children with complete data, –1.72 (95% CI: –2.95, –0.49); 30-month PDI; all children, –0.54 (95% CI: –1.64, 0.56); children with complete data, –1.74 (95% CI: –3.23, –0.25)]. In the subset of children who provided blood samples at both 12 and 24 months (n = 267 vs. total n = 275 for 12-month samples), results from 12-month metal analyses were similar [e.g., mixed-effects model adjusted β, manga- nese quintile 5 × continuous lead predicting MDI: subset of 267 children, –1.26 (95% CI: –2.17, –0.37); total sample, –1.27 (95% CI: –2.18, –0.37)]. For 24-month metal analyses, results for MDI among the subset of 267 chil- dren with both 12- and 24-month blood sam- ples were generally consistent with results based on all 24-month samples [n = 437; mixed- effects model adjusted β, manganese quintile 5 × continuous lead: subset of 267 children, –0.53 (95% CI: –1.41, 0.35); total sample, –0.09 (95% CI: –0.63, 0.45)]. For PDI, however, we observed a negative interaction between 24-month lead and manganese only among the subset of children with both 12- and 24-month blood samples [mixed-effects model adjusted β, manganese quintile 5 × continuous lead: subset, –0.86 (95% CI: –1.66, –0.05); total sample, 0.18 (95% CI: –0.32, 0.68)]. When we excluded six outliers of 12-month blood levels (three highest man- ganese and lead levels) from analyses, effect estimates for the interaction between lead and high manganese on neurodevelopment were similar [e.g., mixed-effects model adjusted Outcome MDI 12 months 18 months 24 months 30 months 36 months PDI 12 months 18 months 24 months 30 months 36 months 125 105 I D M h ton 85 m - 8 1 65 45 110 I D hP 90 t n o m - 4 2 70 50 125 105 I D M h ton 85 m - 8 1 65 45 110 I D P 90 h t n o m - 4 2 70 50 Environmental Health Perspectives • volume 120 | number 1 | January 2012 129 10 BPb (µg/dL) 15 0 5 20 0 5 10 BPb (µg/dL) 15 20 Figure 1. Scatterplots and regression lines of 12-month blood lead (BPb) and 18-month MDI among chil- dren with 12-month blood manganese (Mn) in quintiles 1–4 (A) and quintile 5 (B). Mn quintiles 1–4 Mn quintile 5 10 BPb (µg/dL) 0 5 15 20 0 5 10 BPb (µg/dL) 15 20 Figure 2. Scatterplots and regression lines of 12-month blood lead (BPb) on 24-month PDI among children with 12-month blood manganese (Mn) in quintiles 1–4 (A) and quintile 5 (B).