Because of ethical and practical concerns about research considering prenatal smoke exposure, maternal cigarette smoking during pregnancy in humans cannot be randomized. The consequence of this is that prenatal smoke exposure effects on human offspring outcomes are, by definition, quasi-experimental in nature (Shadish, Cook, & Campbell, 2002). However, innovative designs such as full sibling pairs discordant for prenatal exposure – an extension of the case-crossover design (D’Onofrio, Singh, Iliadou, Lambe, Hultman, Grann, et al., 2010; D’Onofrio, Singh, Iliadou, Lambe, Hultman, Neiderhiser, et al., 2010; D’Onofrio et al., 2008; Knopik, 2009; Knopik, McGeary, Nugent, Francazio, & Heath, 2010; Kuja-Halkola, et al., 2010; Lumley & Levy, 2000; Meyer, Williams, Hernandez-Diaz, & Cnattingius, 2004) and in vitro fertilization (IVF) cross-fostering approaches (Rice et al., 2009; Rice et al., 2010; Thapar et al., 2007; Thapar et al., 2009) have enabled better control for confounding factors. Results from these studies suggest that some associations suggested between maternal cigarette smoking during pregnancy and offspring behavioral outcomes, a common finding in the larger literature, may indeed be influenced by design limitations, specifically an inability to adequately control
