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However this observational study could be subject to substantial confounding by indication.
There was little evidence of substantial confounding by any risk variables considered.
However, the universal provision of health care considerably reduces the likelihood of substantial confounding by social characteristics.
Under full categorization, an investigator would conclude that there was substantial confounding by comorbidity, and would choose to retain it as an adjustment or stratification variable.
We did not expect substantial confounding by these covariates because they are unlikely to predict genotype, a necessary condition for factors to be confounders.
The similarity between data derived from chamber (eg Operation Everest II [ 29]) and field studies (eg AMREE [ 8, 30]) implies that hypoxia is the over-riding physiological stimulus in field studies and argues against substantial confounding by environmental factors.
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The absence of substantial confounding or interaction by alcohol on these associations was not entirely expected, but appears consistent with other studies.
We additionally examined three-way interactions with race in an analysis that included both site and AIMs and observed no evidence of substantial confounding or effect modification by race.
However, it is unlikely that there is substantial confounding of the treatment-related risks by established risk factors as a strong association between treatment and a risk factor would be required.
Although we were able to control for substantial confounding, our results may still be affected by confounding from unmeasured variables, including lifestyle and other exogenous factors such as smoking status, living standard, BMI, history of imprisonment, homelessness, traveling in high-endemic TB areas, and history of Bacillus Calmette-Guérin vaccination.
Conversely, however, we did not observe evidence of substantial confounding in the models of prenatal major roadway proximity by any of the measured covariates, suggesting that residual confounding by sociodemographic factors is unlikely to explain the observed major roadway proximity cognition associations.
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