Is maternal smoking during pregnancy a causal environmental risk factor for adolescent antisocial behavior? Testing etiological theories and assumptions.

Most research on the association between maternal smoking during pregnancy (SDP) and offspring antisocial behavior (ASB) has been consistent with a causal inference (Ernst, Moolchan, & Robinson, 2001; Olds, 1997; Wakschlag, Pickett, Cook, Benowitz, & Leventhal, 2002). The causal inference has been supported recently by human research, including studies conducted across several countries (Brion, et al., 2010), controlling for numerous confounds (Paradis, Fitzmaurice, Koenen, & Buka, 2010), and that have explored differences in brain structure and functional processes in exposed and unexposed offspring (review in Derauf, Kekatpure, Neyzi, Lester, & Kosofsky, 2009). The results also are consistent with recent basic animal research on brain changes associated with prenatal nicotine exposure, including alterations in nicotinic acetylcholine receptors (e.g., Gold, Keller, & Perry, 2009). Recent quasi-experimental studies in humans, however, have suggested that family background characteristics account for the statistical association between SDP and offspring ASB (review in Knopik, 2009). These studies, which use design features to rule out alternative hypotheses (Rutter, 2007; Shadish, Cook, & Campbell, 2002), suggest that unmeasured risk factors that covary with maternal SDP likely increase risk for ASB in the offspring instead of a direct prenatal environmental influence of SDP on risk for ASB. Several studies on ASB have compared differentially exposed siblings by looking at risk for ASB among offspring where the mother changed her smoking across pregnancies. This design controls genetic and shared environmental factors that are confounded with SDP as alternative explanations for the apparent effect of SDP (Donovan & Susser, 2011; Lahey & D’Onofrio, 2010; Rutter, 2007). If the sibling who was exposed to greater SDP had higher levels of ASB (a within-family association), a causal association would be supported. In contrast, if both siblings had the same level of ASB, the results would suggest SDP does not cause ASB. Gilman, Gardner, & Buka (2008) found that differentially exposed siblings did not vary in their rates of childhood conduct problems. And, D'Onofrio et al. (2008) found that maternal SDP was not associated with increased risk for childhood conduct problems or oppositional problems when comparing differentially exposed siblings. A recent study found comparable results when exploring the association between SDP and offspring criminal convictions during adolescence and early adulthood (D'Onofrio, Singh, Iliadou, Lambe, Hultman, Grann, et al., 2010). These findings were confirmed in a novel in vitro fertilization study of maternal SDP and childhood conduct problems (Rice, et al., 2009), which controls genetic confounds by examining risk factors in women who were not genetically related to their children (Thapar, et al., 2007). Certainly converging evidence across numerous studies and across various designs is necessary to support a causal inference (e.g., Rutter, Pickles, Murray, & Eaves, 2001). It is important to note that the existing quasi-experimental studies on ASB are limited by several problems. First, many of the studies are limited by measurement problems. Many studies relied on the same reporter (the mother) for the assessment of both SDP and ASB (Rutter, 2007). And, one study (D'Onofrio, Singh, Iliadou, Lambe, Hultman, Grann, et al., 2010) has been criticized for using extreme measures of ASB (criminal convictions), that may make the interpretation of findings difficult, if not impossible (Talati & Weissman, 2010). Second, a great majority of the studies are only based on childhood conduct problems, not ASB during adolescence when the societal costs and suffering associated with ASB are greater (e.g., R. Loeber, D. P. Farrington, M. Stouthamer-Loeber, & W. Van Kammen, 1998). Third, the lack of measures of adolescent ASB also is problematic because SDP may differentially influence specific developmental trajectories of ASB. One study suggests that SDP may be more strongly associated with early-starting and chronic forms of ASB (Brennan, Grekin, & Mednick, 1999), which is consistent with the current theories suggesting that the trajectory of ASB is associated with early neurocognitive deficits (e.g., Moffitt, 2006). Fourth, few of the quasi-experimental studies have been able to test the assumptions inherent in their designs. For example, the sibling-comparison design has a number of limitations, including the inability account for whether exposure to the risk in one pregnancy carries over to other pregnancies, historical changes, and factors that influence why women change their smoking behavior over time (Donovan & Susser, 2011; Lahey & D’Onofrio, 2010). The current study sought to address these issues by: (a) examining the associations between SDP and multiple measures of ASB in a large study of offspring of a representative sample of women in the United States, (b) investigating these associations while comparing differentially exposed siblings with the same biological mothers, and (c) testing assumptions inherent in the sibling-comparison design.