The current study combined two general quasi-experimental approaches to study the mechanisms through which SDP influences offspring AA. The study relied on the historical decline in SDP, due in part to public health campaigns to deter pregnant women and women of childbearing ages from smoking (Cnattingius, 2004
), to explore whether variations in SDP by the same mother were associated with differences in her offspring’s AA. The study also utilized a large family study, including a mixture of sibling and cousin types, to compare relatives who differ in their exposure to SDP and
who vary in the degree to which they share genetic risk associated with SDP. By combining these two approaches, the current study sought to pull apart the co-occurring genetic and environmental risks associated with SDP.
The results provide support for two main conclusions. First and foremost, the results strongly suggest that SDP does not cause offspring to have lower AA. We compared full siblings who were differentially exposed to SDP, an approach that accounts for the genetic factors and environmental factors that siblings share (Lahey et al., in press
; Rutter, 2007
). If SDP causes offspring to have lower AA, perhaps through the neurotoxic effects of exposure to prenatal nicotine, then a child exposed to SDP would be expected to have poorer AA than his/her sibling who was not exposed. For both school grades and mathematics proficiency, however, full siblings differentially exposed to SDP did not differ in their levels of AA. The results strongly suggest that familial risks correlated with SDP, and not the specific effects of SDP, are responsible for the lower AA found in offspring whose mothers smoked during pregnancy. The findings are consistent with previous research on the role of SDP and AA in Sweden (Lambe et al., 2006
), as well as a sibling comparison study of conduct problems in the U.S. (D’Onofrio et al., 2008
) and a children of twins study of ADHD in Australia (Knopik et al., 2005
). The results are also consistent with traditional family studies that used extensive covariates (Batty et al., 2006
; Fergusson & Lloyd, 1991
). These designs, however, do not explain why SDP is associated with lower levels of AA in the population.
The second conclusion involves the underlying processes by which SDP is associated with AA. The results suggest that genetic factors passed from parents to their offspring (passive gene-environment correlation) account for at least part of the statistical association. Genetic factors are implicated because the degree to which relatives were genetically correlated moderated the association between SDP and AA when comparing types of cousins and types of siblings. Models 4 and 5, in fact, provided statistical tests of these differences. When relatives were more genetically similar (full cousins versus half cousins and full siblings versus half siblings), the association between SDP and AA was weaker. Stated differently, when genetic factors were more controlled (by comparing relatives who shared more genetic factors), the association between SDP and AA went down. graphically illustrates this finding. It is important to note that the findings were consistent across levels of analysis (i.e. the comparisons of half versus full cousins were similar to those comparing full and half siblings) and measures of AA, which provides converging evidence for the confounding role of genetic factors.
We stress that the results do not prove that the underlying causal mechanisms are genetic—the findings only suggest that genetic factors confound the association (i.e., the results are consistent with the role of genetic confounds). Half cousins and full cousins differ in their genetic relatedness, but they also may differ on environmental risks. Full cousins may see each other (and their aunts) more often than half cousins, which could make full cousins more similar if the level of contact influenced AA—the equal environments assumption one generation removed (D’Onofrio et al., 2003
). Offspring of half siblings may also be exposed to more environmental risk than offspring of full siblings, which could influence the variability in AA. Similarly, there may be differences in the variability of AA between half and full siblings. These limitations, which apply to all step-family behavioral genetic designs (e.g., Reiss, Neiderhiser, Hetherington, & Plomin, 2000
), need to be tested in future studies. Using the Children of Twins Design would help test these assumptions. Studies of adult twins frequently include measures of contact between the twins (and their families), which could help account for differences in levels of family contact. Differences in genetic risk among cousins also would not be based on comparing offspring from intact families to those from divorced/separated parents; rather, differences in genetic relatedness among cousins in the Children of Twins design are due to the zygosity type of the adult twins.
The comparison of fathers of half siblings discordant for exposure to prenatal smoking indicated that the father of the child exposed to SDP more often had a history of criminal convictions. Exposure to prenatal smoking, thus, covaries with paternal risk of criminality, even within-families. For the paternal phenotype to influence a genetic association between mother and offspring, the paternal phenotype has to be genetically correlated with the maternal phenotype. It is well-known that there is substantial assortative mating for antisocial behavior (e.g., Krueger, Moffitt, Caspi, Bleske, & Silva, 1998
), and in the current sample women with a history of a criminal conviction were much more likely to have children with men with convictions (OR = 3.38, CI = 3.32 – 3.46). Thus, the pattern of associations between SDP and AA for half- and full siblings is congruent with genetic confounding, even though environmental explanations cannot be excluded. Additional research is required to further delineate the underlying causal mechanisms.
The fact that SDP is associated with lower AA in half siblings provides compelling evidence that researchers must explore the role of fathers when studying the putative effects of SDP. Although most research on SDP has not included measured characteristics of the fathers (review in Maughan et al., 2004
), the current results indicate that characteristics of fathers, whether due to genetic risk passed down to the children or psychosocial risk factors, help explain some of the association between SDP and offspring AA.
In addition to the ability to use quasi-experimental approaches to study the risks associated with SDP, the current study also benefits from a number of key strengths. The study was conducted on a large, national sample of offspring. The analyses also included two measures of AA, school grades and mathematics proficiency. The inclusion of the mathematics scores greatly helps the interpretation of the data because the assessment was standardized across the entire study. School grades could vary substantially by schools or communities. The fact that both measures of AA provide similar results provides converging evidence for the conclusions drawn. The large sample size also permits the comparison of unique types of relatives (e.g., half siblings differentially exposed to SDP) that would be hard to find using traditional samples. SDP was also assessed during pregnancy rather than relying on maternal retrospective reports, a key limitation of some of the previous sibling comparison tests of SDP (Rutter, 2007
). The analyses were also able to include measured covariates of both mothers and
fathers. The exclusion of paternal information is a key limitation of previous research on SDP (Maughan et al., 2004
There are also a number of limitations of the current study. The measure of SDP was based on maternal report, usually during the beginning of her pregnancy. Exposure to smoking later in life was also not available. Therefore, the study cannot explore whether the timing of the exposure was critical for later AA. The study could also not explore the importance of paternal smoking during pregnancy. The analyses also did not study whether individual or familial factors moderate the association between SDP and offspring AA. Research has suggested that factors, such as offspring sex and birth complications (Brennan, Grekin, & Mednick, 1999
), interact with SDP to substantially increase risk for poor offspring adjustment. The comparison of siblings differentially exposed relies on assumptions that mothers who vary their smoking across pregnancies are comparable to those who smoked during every pregnancy (D’Onofrio et al., 2008
). Furthermore, the analyses did not estimate the degree to which environmental and genetic confounds explain the association between SDP and AA. The results imply that genetic factors (and environmental confounds) are important. We are currently working on the analytical models required to specifically quantify the role of genetic and environmental factors when studying exposure to SDP with the various types of relative pairs available. More research, therefore, is needed to understand the causal process responsible for the association between SDP and poor offspring AA.
Overall, the study illustrates the importance of quasi-experimental approaches to studying putative environmental risk factors (Moffitt, 2005
; Rutter, 2007
). Similar to the two previous sibling comparison studies of SDP (D’Onofrio et al., 2008
; Lambe et al., 2006
), we would have drawn the wrong conclusion about the role of SDP if we only relied on the statistical covariates to account for confounds. Even though the regression analyses on the epidemiological sample controlled for measures of maternal and paternal traits, we would have wrongly concluded that SDP had an independent association with AA after controlling for maternal and paternal characteristics, consistent with a causal inference.
Finally, it is important to emphasize that the current results do not suggest that SDP has no impact on offspring adjustment. The results are limited to measures of AA at age 15 only. The findings for birth weight suggest, as have previous genetically informed (D’Onofrio et al., 2003
) and other quasi-experimental studies (Cnattingius, 2004
), that SDP has a specific effect on offspring birth weight that is environmentally mediated. SDP appears to impact particular outcomes more strongly than others, particularly poor pregnancy outcomes (Cnattingius, 2004
). Reducing SDP, therefore, remains a major public health issue.