1 eTable 1. Baseline Characteristics of Study Participants Included and Excluded in the Analysesa Included (n = 4350) Excluded (n = 1476) Boys 2176 (50) 861 (59) Maternal asthma 65 (2) 49 (4) Paternal asthma 83 (2) 43 (3) Fetal tobacco smoke exposureb 925 (22) 262 (22) Environmental tobacco smoke exposurec 1377 (32) 401 (33) Less than high school diploma 196 (5) 48 (4) High school diploma 2348 (57) 690 (59) More than high school diploma 1612 (39) 433 (37) Less than high school diploma 185 (4) 58 (5) High school diploma 1846 (44) 507 (43) More than high school diploma 2157 (52) 625 (53) Maternal education Paternal education 1 Fish intake None 75 (3) 26 (5) Once/wk 1379 (48) 255 (46) 2–3 times/wk 1227 (43) 242 (43) 4–5 times/wk 126 (4) 23 (4) >5 times/wk 43 (2) 11 (2) 1271 (29) 393 (27) Pet ownership 2 Abbreviation: Hg, mercury. 3 aResults 4 and excluded groups. 5 bActive 6 cPresence are shown as n (percentage). The outcome data represent 2 tests of the difference between the children in the included maternal smoking or presence of a smoker at home during pregnancy. of a smoker at home after delivery. 7 2 8 eTable 2. Distribution of Blood Hg Concentrations among the Study Participants during the Study Period Selected percentiles Biomarker No. of GM (GSD) 10th 25th 50th 75th 90th 95th observations 9 Blood Hg at 7–8 y (µg/L) 4350 2.02 (2.01) 0.89 1.42 2.17 3.24 4.34 5.14 Blood Hg at 9–10 y (µg/L) 3165 1.79 (1.83) 0.89 1.30 1.89 2.64 3.51 4.18 Blood Hg at 11–12 y (µg/L) 2088 1.96 (1.79) 0.98 1.40 2.03 2.81 3.94 4.95 Abbreviations: Hg, mercury; GM, geometric mean; GSD, geometric standard deviation. 10 3 11 eTable 3. Association of Hg Concentration with Asthma at 9–10 and 11–12 Years of Age, Stratified by Gendera Asthma at 9–10 y Asthma at 11–12 y Incident Asthma OR 95% CI OR 95% CI HR 95% CI Boys 1.80 1.18–2.73 1.35 0.98–1.86 1.54 1.12–2.10 Girls 1.41 0.93–2.13 1.18 0.84–1.66 1.26 0.90–1.76 12 Abbreviations: CI, confidence interval; Hg, mercury; HR, hazards ratio; OR, odds ratio. 13 aModels 14 paternal and maternal education level, and pet ownership. were adjusted for gender, paternal and maternal asthma history, fetal and environmental tobacco smoke exposure, 15 4 16 eTable 4. Association between Blood Hg Concentration and Asthma-related Outcomes at Ages Up to 11–12 Years after Inverse 17 Probability Weighting for Follow-upa Wheezingb Log Hg (µg/L) Asthma medication usec Airway hyperresponsivenessd OR 95% CI OR 95% CI OR 95% CI 1.16 1.00–1.36 1.40 0.93–2.09 1.16 0.99–1.36 18 Abbreviations: CI, confidence interval; Hg, mercury; OR, odds ratio. 19 aModels 20 paternal and maternal education level, and pet ownership. 21 bPositive response to the question “Has your child experienced wheezing in the past 12 months?”. 22 cPositive response to the question “Did your child use asthma medication in the past 12 months?”. 23 dDefined as a methacholine provocative concentration producing a 20% fall in forced expiratory volume in 1 second of≤8 mg/mL. were adjusted for gender, paternal and maternal asthma history, fetal and environmental tobacco smoke exposure, 5 24 eTable 5. Association of Blood Hg Concentration with Asthma at 9–10 and 11–12 Years of Age in Children with Fish Consumption 25 Informationa Asthma at 9–10 y of Age Asthma at 11–12 y of Age No.b OR 95% CI No.b OR 95% CI Hg at 7–8 y 79/2144 1.66 1.14–2.43 113/1287 1.39 1.03–1.88 Average Hg until 7–8 yc 79/2144 1.48 0.91–2.41 113/1287 1.33 0.89–1.99 NA NA NA 113/1287 1.36 0.83–2.24 Average Hg until 11–12 yd 26 Abbreviations: CI, confidence interval; Hg, mercury; OR, odds ratio. 27 aModels 28 paternal and maternal education level, and pet ownership. were adjusted for gender, paternal and maternal asthma history, fetal and environmental tobacco smoke exposure, 6 29 bNumber with outcome/total number for analysis. 30 cAverage blood Hg concentration at 7–8 and 9–10 years of age. 31 dAverage blood Hg concentration at 7–8, 9–10, and 11–12 years of age. 32 7 33 eTable 6. Association of Hg Concentration at 7–8 Years of Age with Immune System Blood Profile at Ages Up to 11–12 Years, 34 Stratified by Occurrence of Current Asthma in Children With Fish Consumption Informationa Total (n = 2850) WBC count Children With Children Without Asthma (n = 113) Asthma (n = 2737) β 95% CI β 95% CI β (SE) 95% CI -0.02 -0.03 to -0.01 0.01 -0.05 to 0.07 -0.02 -0.03 to 0.003 Segment neutrophil % 0.05 -0.34 to 0.45 1.72 -0.06 to 3.49 -0.01 -0.57 to 0.54 Lymphocyte % 0.003 -0.39 to 0.39 -1.68 -3.55 to 0.19 0.08 -0.48 to 0.63 Monocyte % -0.0004 -0.01 to 0.01 0.004 -0.05 to 0.06 0.001 -0.01 to 0.02 Basophil % 0.007 -0.01 to 0.03 0.07 -0.04 to 0.17 0.01 -0.01 to 0.04 hs-CRP 0.08 0.02 to 0.14 0.40 0.12 to 0.68 0.06 -0.03 to 0.15 Total IgE -0.06 -0.13 to 0.02 0.04 -0.38 to 0.45 -0.05 -0.16 to 0.06 35 Abbreviations: CI, confidence interval; Hg, mercury; hs-CRP, high-sensitivity C-reactive protein; OR, odds ratio; SE, standard error; 36 WBC. white blood cell. 37 aModels were adjusted for gender, paternal and maternal asthma history, fetal and environmental tobacco smoke exposure, 8 38 paternal and maternal education level, fish intake, and pet ownership. The association of Hg with hs-CRP and total IgE in the total 39 population and the association of Hg with total IgE in children without current asthma were also adjusted for these covariates 40 except for paternal education because of a convergence problem. WBC count, monocyte percentage, basophil percentage, hs- 41 CRP, and total IgE were log-transformed for normal approximation. 42 9 43 eTABLE 7. Association between Blood Hg Concentration and Asthma at 9–10 and 11–12 Years of Age, Adjusted for Citya Asthma at 9–10 y of Age Asthma at 11–12 y of Age No.b OR 95% CI No.b OR 95% CI Hg at 7–8 y 129/3197 1.46 1.07–2.00 191/2179 1.33 1.04–1.71 Average Hg until 7–8 yc 129/3197 1.62 1.10–2.37 191/2179 1.23 0.91–1.67 NA NA NA 191/2179 1.23 0.85–1.78 Average Hg until 11–12 yd 44 Abbreviations: CI, confidence interval; Hg, mercury; OR, odds ratio. 45 aModels 46 paternal and maternal education level, pet ownership, and city from which the study participants were recruited. 47 bNumber were adjusted for gender, paternal and maternal asthma history, fetal and environmental tobacco smoke exposure, with outcome/total number for analysis. 10 48 cAverage blood Hg concentration at 7–8 and 9–10 years of age. 49 dAverage blood Hg concentration at 7–8, 9–10, and 11–12 years of age. 50 11 51 eTable 8. Association between Blood Hg Concentration and Asthma-related Outcomes at Ages Up To 11–12 Years, Adjusted for 52 Citya Wheezingb Log Hg (µg/L) Asthma medication usec Airway hyperresponsivenessd OR 95% CI OR 95% CI OR 95% CI 1.21 1.06–1.38 1.45 0.99–2.12 1.12 0.98–1.29 53 Abbreviations: CI, confidence interval; Hg, mercury; OR, odds ratio. 54 aModels 55 paternal and maternal education level, pet ownership, and city from which the study participants were recruited. 56 bPositive response to the question “Has your child experienced wheezing in the past 12 months?”. 57 cPositive response to the question “Did your child use asthma medication in the past 12 months?”. 58 dDefined as a methacholine provocative concentration producing a 20% fall in forced expiratory volume in 1 second of≤8 mg/mL. were adjusted for gender, paternal and maternal asthma history, fetal and environmental tobacco smoke exposure, 12