Use of ultra-high-risk AD families can be viewed as either a strength or weakness of our findings. On the positive side, use of these families to assess the impact of prenatal substance use provides a unique opportunity to increase the familial/genetic susceptibility for substance use disorders while examining the specific drug use behaviors of women during their pregnancies. However, it must be acknowledged that these families are not representative of AD families in the general population. Follow-up of offspring from these multiplex families indicates an exceptionally high rate of AD and substance use by young adulthood (Hill et al., 2008, Hill et al., 2011). Although these families may not be representative of AD families in the general population, the study of multiplex families provides an efficient means for identifying risk factors that can then be taken to population samples for replication.