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1 Asthma trajectories in a population-based birth cohort: Impact of environmental exposures Hind Sbihi 1, Mieke Koehoorn 1, Lillian Tamburic 1, Michael Brauer 1 1 School of Population and Public Health, University of British Columbia, Canada Supplementary Materials Table S 1 Tukey s post hoc tests of difference between group* means. The Tukey comparisons between group means that are significant are indicated by ***... 2 Table S 2- Selection of trajectory membership based on model fit Statistics for different groups and orders Table S 3: Posterior probability for each trajectory (Non-Asthmatics; Transient; LICA: Late Infancy Chronic Asthma; EICA: Early Infancy Chronic Asthma) and 95% confidence intervals... 4 Table S 4 Odds Ratios of adhering to one of three asthma trajectory groups (T: Transient; LICA: Late Infancy Chronic Asthma onset; EICA: Early Infancy Chronic Asthma onset) relative to non-asthma trajectories based on weighted multinomial logistic regressions for individual and neighborhood-level risk factors Table S 5- Exposure levels of greenness, IDW derived air pollutants and fine particulate matter estimates from Land Use Regression model by trajectory in 68,195 BAQS children followed from 1999 to Table S 6: Distribution of age at diagnosis confirmed using billing codes from physicians (MSP) or hospital separation files (HSP) by number of years of registration with the universal medical health insurance during study follow-up ( )... 9 Table S 7 - Summary statistics of number of elapsed years of data coverage by birth year Figure S 1: Diagram of twotired analyses to (1) define asthma trajectories using Group-Based Trajectory Modeling (GBTM) and (2) identify environmental and individual factors associated with these trajectories Figure S 2- Scatter plot matrix of greenness, PM 2.5 and IDW-derived air pollutants by asthma group (nonasthmatics are excluded in this data)

2 Table S 1 Tukey s post hoc tests of difference between group* means. Statistically significant Tukey comparisons between group means are indicated by *** Birth Weight at delivery (grams) Difference 95% Confidence Interval Non-asthma Transient *** Non-asthma LO CA *** Non-asthma EOCA *** Transient LO CA Transient EO CA *** LOCA EO CA Gestational length (weeks) Non-asthma LO CA *** Non-asthma Transient *** Non-asthma EO CA *** LO CA Transient *** LO CA EO CA *** Transient EO CA *LOCA: Late Onset chronic asthma trajectory; EOCA: Early OnsetChronic Asthma trajectory E2

3 Table S 2- Selection of trajectory membership based on model fit Statistics for different groups and orders. model 0 model1 model2 model3 model4 model5 model6 model7 Groups * Order ** BIC Log likelihood * Number of trajectories considered. ** Order defines the shape of each trajectory (0 for constant, 1 for linear, 2 for quadratic, 3 for cubic) E3

4 Table S 3: Posterior probability for each trajectory (Non-Asthmatics; Transient; LOCA: Late Onset Chronic Asthma; EOCA: Early Onset Chronic Asthma) and 95% confidence intervals p(non asthma) p(transient) p(loca) p(eoca) [0.01 ; 0.01] 0.23 [0.21 ; 0.25] 0.00 [0 ; 0] 0.15 [0.13 ; 0.18] [0.01 ; 0.01] 0.38 [0.36 ; 0.40] 0.00 [0 ; 0] 0.43 [0.39 ; 0.46] [0.01 ; 0.01] 0.41 [0.39 ; 0.43] 0.03 [0.02 ; 0.04] 0.65 [0.62 ; 0.68] [0.01 ; 0.01] 0.34 [0.31 ; 0.36] 0.14 [0.12 ; 0.16] 0.75 [0.73 ; 0.78] [0.01 ; 0.01] 0.22 [0.21 ; 0.24] 0.31 [0.28 ; 0.33] 0.78 [0.76 ; 0.8] [0.01 ; 0.01] 0.12 [0.10 ; 0.13] 0.41 [0.39 ; 0.44] 0.76 [0.73 ; 0.78] [0 ; 0.01] 0.06 [0.05 ; 0.06] 0.42 [0.4 ; 0.45] 0.69 [0.66 ; 0.71] [0 ; 0.01] 0.03 [0.02 ; 0.03] 0.37 [0.35 ; 0.39] 0.58 [0.55 ; 0.61] [0 ; 0] 0.02 [0.01 ; 0.02] 0.29 [0.27 ; 0.31] 0.45 [0.42 ; 0.48] [0 ; 0] 0.02 [0.01 ; 0.03] 0.22 [0.2 ; 0.24] 0.33 [0.29 ; 0.36] [0 ; 0] 0.02 [0.01 ; 0.03] 0.18 [0.15 ; 0.21] 0.24 [0.19 ; 0.29] E4

5 Table S 4 Odds Ratios of adhering to one of three asthma trajectory groups (T: Transient; LICA: Late Infancy Chronic Asthma onset; EICA: Early Infancy Chronic Asthma onset) relative to non-asthma trajectories based on weighted multinomial logistic regressions for individual and neighborhood-level risk factors. Effect Category Group Standardized Estimate Odds Ratio 95% Wald CI p-value Smoking Yes vs No T Smoking Yes vs No LOCA Smoking Yes vs No EOCA Sex F vs M T <.0001 Sex F vs M LOCA <.0001 Sex F vs M EOCA <.0001 Parity 1 vs 0 T <.0001 Parity 1 vs 0 LOCA <.0001 Parity 1 vs 0 EOCA Maternal age 1 st vs 3 rd tertiles T Maternal age 1 st vs 3 rd tertiles LOCA Maternal age 1 st vs 3 rd tertiles EOCA Maternal age 2 nd vs 3 rd tertiles T Maternal age 2 nd vs 3 rd tertiles LOCA Maternal age 2 nd vs 3 rd tertiles EOCA Delivery C-section vs vaginal T Delivery C vs. V LO CA Delivery C vs. V EO CA SES High vs Low T SES H vs L LOCA SES H vs L EOCA Education H vs L T <.0001 Education H vs L LOCA Education H vs L EOCA Breastfeeding No vs Yes T E5

6 Breastfeeding No vs Yes LOCA Breastfeeding No vs Yes EOCA Birth weight 2500 vs <2500 g T Birth weight 2500 vs <2500 g LOCA Birth weight 2500 vs <2500 g EOCA <.000 Gestation 37 vs <37 weeks T Gestation 37 vs <37 weeks LOCA Gestation 37 vs <37 weeks EOCA χ 2 (30) <0.001, N= (3931 observations were deleted due to missing values for the explanatory variables). E6

7 Table S 5- Exposure levels of greenness, IDW derived air pollutants and fine particulate matter estimates from Land Use Regression model by trajectory in 68,195 BAQS children followed from 1999 to 2009 Exposure Trajectory N Median Mean SD Min Max Greenness No Asthma Transient LOCA EOCA All Carbon Monoxide No Asthma Transient LOCA EOCA All Nitrogen Monoxide Nitrogen Dioxide No Asthma Transient LOCA EOCA All No Asthma Transient LOCA EOCA All No Asthma Transient Ozone PM 10 LOCA EOCA All No Asthma Transient LOCA E7

8 EOCA All No Asthma PM 2.5 Transient LOCA EOCA All No Asthma Transient SO 2 PM 2.5 LOCA EOCA All No Asthma Transient LOCA EOCA All E8

9 Table S 6: Distribution of age at diagnosis confirmed using billing codes from physicians (MSP) or hospital separation files (HSP) by number of years of registration with the universal medical health insurance during study follow-up ( ) Age type Full years elapsed from birthdate to end of last registration Total N (%) 0 MSP (6.59) HSP (6.98) 1 MSP (12.92) HSP (23.43) 2 MSP (13.29) HSP (23.58) 3 MSP (14.06) HSP (15.46) 4 MSP (13.68) HSP (10.83) 5 MSP (13.14) HSP (8.12) 6 MSP (10.52) HSP (6.2) 7 MSP (7.52) HSP (2.99) 8 MSP (4.92) HSP (1.78) 9 MSP (2.52) HSP (0.43) 10 MSP (0.85) HSP (0.21) Total MSP HSP E9

10 Table S 7 - Summary statistics of number of elapsed years of data coverage by birth year. Cohort (Birth year) Code N Mean Min Max A: Born in B: Born in C: Born in D: Born in E10

11 Figure S 1: Diagram depicting analytical methodology: two stage analyses to (1) define asthma trajectories using Group- Based Trajectory Modeling (GBTM) and (2) identify environmental and individual factors associated with these trajectories. E11

12 Figure S 2- Scatter plot matrix of greenness, PM 2.5 and IDW-derived air pollutants by asthma group (non-asthmatics are excluded in this data).t: Transient trajectory; LI CA: Late onset trajectory; EI CA: Early Onset Trajectory E12

Figure S1. Flowchart of sample included in the analysis.

Figure S1. Flowchart of sample included in the analysis. 3098 mother/infant pairs with EMR records of well-child and specialty visits 418 cases with any ADHD diagnosis 94 cases with any ASD diagnosis while