Abstract
BackgroundThe variable “small for gestational age,” frequently defined as birth weight below the 10th percentile in a gestational age and sex-normalized population, is nowadays generally perceived as a more adequate measure than birth weight or low birth weight (birth weight < 2500 g) to capture fetal growth. However, the use of small for gestational age rather than birth weight or low birth weight as an outcome (dependent) variable may have important impacts on the interpretation of analyses aimed at estimating the causal effect of an exposure of interest on infants. We hypothesized potential differences in both types of effects estimated (direct or total) and in ability to control for confounding bias.MethodsWe first examined the use of outcome variables birth weight and small for gestational age to get insights on modeling practices within the field of maternal asthma. Using directed acyclic graph simulations where gestational age was a potential mediator, we then compared estimated exposure effects in regression models for birth weight, low birth weight, and small for gestational age. Graphs with and without confounding were considered.ResultsOur simulations showed that the variable small for gestational age captures the direct effect of exposure on birth weight, but not the indirect effect of exposure on birth weight through gestational age. Interestingly, exposure effect estimates from small for gestational age models were found unbiased whenever exposure effect estimates from birth weight models were affected by collider bias due to conditioning on gestational age in the models.ConclusionsThe sole consideration of the outcome small for gestational age in a study may lead to suboptimal understanding and quantification of the underlying effect of an exposure on birth weight-related measures. Instead, our results suggest that both outcome variables (low) birth weight and small for gestational age should minimally be considered in studies investigating perinatal outcomes.
Highlights
The variable “small for gestational age,” frequently defined as birth weight below the 10th percentile in a gestational age and sex-normalized population, is nowadays generally perceived as a more adequate measure than birth weight or low birth weight to capture fetal growth
We observe that Inhaled corticosteroids (ICS) is not associated with Small for gestational age (SGA) (M4), nor is it with birth weight (BW) when we condition on gestational age (GA) (M2)
Using Directed acyclic graph (DAG) where GA was a potential mediator between the exposure and BW, we have confirmed that SGA is an absorbing variable: the observed association between the exposure and SGA solely reflects the direct effect of the exposure on BW, effect which could be interpreted as a manifestation of intrauterine growth retardation
Summary
The variable “small for gestational age,” frequently defined as birth weight below the 10th percentile in a gestational age and sex-normalized population, is nowadays generally perceived as a more adequate measure than birth weight or low birth weight (birth weight < 2500 g) to capture fetal growth. The use of small for gestational age rather than birth weight or low birth weight as an outcome (dependent) variable may have important impacts on the interpretation of analyses aimed at estimating the causal effect of an exposure of interest on infants. The variable SGA, frequently defined as BW below the 10th percentile in a gestational age (GA) and sexnormalized population [4, 5], is generally accepted as a more adequate measure than BW or LBW to characterize intrauterine growth [2, 6]. While much of recent focus is put on the epidemiology of preterm birth and SGA (e.g., [1, 7]), the use of SGA rather than (L)BW itself as an outcome (dependent) variable may have
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