Effect measure modification summary

(4.1) 7.5 (0) 3.67 (3.29) 3.89 (2.62) 0.51 (0.61)

8.3 Effect measure modification summary

Table 42 summarizes the significant effect measure modification results, using a

criterion of p<.01. Given the large number of tests of effect measure modification, we focused on looking at consistent patterns (that is, consistent effects across multiple outcome measures and multiple thyroid function biomarkers). There were no clearly consistent effects, though

selenium’s modification of the association between TSH and two tasks of inhibition is of interest (see Figure 14 for stratified estimates).

Table 43 summarizes significant effect measure modification results among ADHD cases only (again using a criterion of p<.01), and table 44 summarizes effect measure modification

results among clinical controls only. Given the small sample size in each group, it is difficult to interpret differences in effect measure modification patterns.

125

Table 42. Summary of significant effect measure modification of the association between maternal thyroid function biomarkers and offspring executive function in the preschool ADHD case-cohort study nested within the Norwegian Mother and Child Cohort (MoBa), 2003–2008.

TSH TT3 fT3i TT4 fT4i

SB5 WM WM Index Verbal WM Non-Verbal WM NEPSY Statue Task Cookie Delay Task BRIEF-Teacher Working Memory Inhibition Emotional Control BRIEF-Parent Working Memory Inhibition Emotional Control

Abbreviations: Attention Deficit Hyperactivity Disorder (ADHD), Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P), Norwegian Mother and Child Birth Cohort (MoBa), A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet Intelligence Scales, Fifth Edition (SB-5), thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine index (fT3i), free thyroxine index (fT4i), working memory (WM).

Note: We tested effect measure modification using augmented product term models, in which an interaction term between the modifier and all other predictors in the model are included in addition to all main effect terms.207 _{This method allows for covariate variation across strata of the potential effect}

measure modifier. We investigated the interaction between maternal DIO1 and DIO2 SNPs and maternal thyroid function biomarkers TT3, fT3i, TT4, and fT4i and the interaction between child DIO2 SNPs and maternal TT4 and fT4i. SNPs were modelled genotypically. TSH, TT3, TT4, fT3i, and fT4i were standardized and modeled linearly. Adjustment factors in the models estimating the effect of maternal thyroid function included: maternal smoking during pregnancy, maternal age, maternal self-reported history of depression, maternal self-reported symptoms of ADHD, and child sex). All models were weighted by the inverse probability of being a preschool ADHD case. Only effect measure modification effects that were statistically significant at p<.01 are presented in this table.

Legend

Maternal rs2235544 Maternal rs225014 Maternal iodine intake (Jod)

127

Figure 14. Maternal selenium-stratified estimated associations between maternal TSH the NEPSY statue task and the cookie delay task. TSH were standardized and modelled linearly. Outcome measures were also standardized. Adjustment factors included: maternal smoking during pregnancy, maternal age, maternal self-reported history of depression, maternal self-reported symptoms of ADHD, and child sex. All models were weighted by the inverse probability of being a preschool ADHD case. Labels inset in the graph are the genotype-specific standardized beta coefficient and 95% confidence interval for the association between the thyroid hormone and the outcome measure.

Abbreviations: Attention Deficit Hyperactivity Disorder (ADHD), Norwegian Mother and Child Birth Cohort (MoBa), confidence interval (CI), single nucleotide polymorphism (SNP), total thyroxine (TT4), free thyroxine index (fT4i).

Table 43. Summary of significant effect measure modification of the association between maternal thyroid function biomarkers and offspring executive function in the preschool ADHD case-cohort study nested within the Norwegian Mother and Child Cohort (MoBa), 2003–2008, among cases only (N=260)

TSH TT3 fT3i TT4 fT4i

SB5 WM WM Index Verbal WM Non-Verbal WM NEPSY Statue Task Cookie Delay Task BRIEF-Teacher Working Memory Inhibition Emotional Control BRIEF-Parent Working Memory Inhibition Emotional Control

Abbreviations: Attention Deficit Hyperactivity Disorder (ADHD), Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P), Norwegian Mother and Child Birth Cohort (MoBa), A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet Intelligence Scales, Fifth Edition (SB-5), thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine index (fT3i), free thyroxine index (fT4i), working memory (WM).

Note: We tested effect measure modification using augmented product term models, in which an interaction term between the modifier and all other predictors in the model are included in addition to all main effect terms.207 _{This method allows for covariate variation across strata of the potential effect}

measure modifier. We investigated the interaction between maternal DIO1 and DIO2 SNPs and maternal thyroid function biomarkers TT3, fT3i, TT4, and fT4i and the interaction between child DIO2 SNPs and maternal TT4 and fT4i. SNPs were modelled genotypically. TSH, TT3, TT4, fT3i, and fT4i were standardized and modeled linearly. Adjustment factors in the models estimating the effect of maternal thyroid function included: maternal smoking during pregnancy, maternal age, maternal self-reported history of depression, maternal self-reported symptoms of ADHD, and child sex). All models were weighted by the inverse probability of being a preschool ADHD case. Only effect measure modification effects that were statistically significant at p<.01 are presented in this table.

129 Legend

Maternal rs2235544 Maternal rs225014 Maternal iodine intake (Jod)

Maternal selenium intake Child rs225014 Child sex (kjonn)

Table 44. Summary of significant effect measure modification of the association between maternal thyroid function biomarkers and offspring executive function in the preschool ADHD case-cohort study nested within the Norwegian Mother and Child Cohort (MoBa), 2003–2008, among controls only (N=82)

TSH TT3 fT3i TT4 fT4i

SB5 WM WM Index Verbal WM Non-Verbal WM NEPSY Statue Task Cookie Delay Task BRIEF-Teacher Working Memory Inhibition Emotional Control BRIEF-Parent Working Memory Inhibition Emotional Control

Abbreviations: Attention Deficit Hyperactivity Disorder (ADHD), Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P), Norwegian Mother and Child Birth Cohort (MoBa), A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet Intelligence Scales, Fifth Edition (SB-5), thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine index (fT3i), free thyroxine index (fT4i), working memory (WM).

Note: We tested effect measure modification using augmented product term models, in which an interaction term between the modifier and all other predictors in the model are included in addition to all main effect terms.207 _{This method allows for covariate variation across strata of the potential effect}

measure modifier. We investigated the interaction between maternal DIO1 and DIO2 SNPs and maternal thyroid function biomarkers TT3, fT3i, TT4, and fT4i and the interaction between child DIO2 SNPs and maternal TT4 and fT4i. SNPs were modelled genotypically. TSH, TT3, TT4, fT3i, and fT4i were standardized and modeled linearly. Adjustment factors in the models estimating the effect of maternal thyroid function included: maternal smoking during pregnancy, maternal age, maternal self-reported history of depression, maternal self-reported symptoms of ADHD, and child sex). All models were weighted by the inverse probability of being a preschool ADHD case. Only effect measure modification effects that were statistically significant at p<.01 are presented in this table.

Legend Maternal rs2235544 Maternal rs225014 Maternal iodine intake (Jod)

Maternal selenium intake Child rs225014 Child sex (kjonn)