We thank Hutcheon et al. for commenting on our article.1 We are in agreement regarding the potential pitfalls of “collider stratification bias,”2 which is conditioning analyses on a variable that is the common effect of multiple causes (e.g., in the case of our article, conditioning on gestational age when assessing the association between gestational weight gain (GWG) and risk of infant mortality). While a discussion of this type of bias is beyond the scope of this communication, we would like to emphasize the importance of subject matter and theoretical considerations when considering the likelihood and extent of such bias. With regard to substantive considerations, Hutcheon et al. assert that
at best, adjustment for gestational age only estimates the association between gestational weight gain and infant death if preterm birth were eliminated, and at worst, introduces additional bias. . . .
This worst-case scenario is based on directed acyclic graphs models in which a risk factor is assumed to be unconditionally independent of the outcome.2 An assumption of unconditional independence is clearly false in the case of GWG and risk of infant mortality.1,3,4 In other words, this worst-case scenario is predicated on a narrow consideration of what is statistically possible rather than biologically plausible. Moreover, as discussed in the paper, our models of the association between GWG and risk of infant mortality included covariates for two preterm birth categories.
As for theoretical considerations, the utility of rigorous methods, such as a weight-gain-for-gestational age z-score,5 to control for confounding by gestational age is incontrovertible. However, nationally representative data sets that allow for the analysis of serial GWG do not exist. Rather, the matter of debate is the degree of residual confounding that may result when regression-based methods are used instead.2,6 On another note, consider our key finding that infants born to underweight, normal-weight, and overweight women with inadequate GWG had odds of mortality during infancy that were respectively 6.18, 1.47, and 2.11 times those of infants born to women with adequate GWG. To attribute these distinct effects solely to confounding one must assume differential confounding within strata of BMI, an unlikely proposition.
We agree with Hutcheon et al. regarding the utility of their approach, and we also stand by our conclusions. We invite readers to evaluate our conclusions in the context of the above-mentioned substantive and theoretical considerations.
References
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