These findings are an important contribution to the extant literature on the etiology of substance use disorders by attempting to disentangle the direct, teratogenic effects of prenatal alcohol, cigarette, and drug exposures from the indirect effects of associated familial background factors on offspring substance use outcomes. Although several studies examining the relationship between offspring substance use and prenatal exposure to alcohol and cigarettes have controlled for a family history of substance use, the drastically different patterns of substance use during pregnancy shown in our High-Risk sample indicate that these statistical procedures may not be sufficient for separating direct, prenatal effects from inherited familial factors that are associated with maternal substance use during pregnancy. Furthermore, studies examining the association between prenatal cigarette exposure and offspring substance use have yielded contrasting results depending on their methodology. Those studies controlling for a family history of SUD support a causal influence of prenatal exposure on offspring substance use (Ernst et al., 2001, Glantz and Chambers, 2006), whereas family-based, quasi-experimental designs indicate that familial background factors explain this association (D’Onofrio et al., 2012, Ellingson et
