Letters to the Editor

Talati & Weissman1 wrote a thoughtful and provocative letter in response to our recent article,2 which suggests that maternal smoking during pregnancy (SDP) does not cause offspring antisocial behavior. We welcome this opportunity to respond.
First, we want to emphasize that reducing SDP remains an important public health issue because SDP is associated with serious pregnancy- related problems (e.g., low birth weight) in studies that have used the most sophisticated statistical and methodological controls for unmeasured confounds that could otherwise explain the association.3
Second, we wholeheartedly agree with Talati's and Weissman's1 call for further research on maternal SDP. Much more research is required, especially research that clarifies the discrepancies among animal studies, smaller human studies with intense measurement, large-scale epidemiological studies, and studies that use quasi-experimental designs. It is important to stress, however, that there is a growing consensus that research in human populations needs to use the best possible methods to identify true causal risk factors.4 Using statistical controls to account for potential confounds, such as parental psychopathology, may be helpful, but researchers cannot draw strong causal inferences from such studies.5
Third, we want to address the major concern that Talati and Weissman raised concerning the interpretation of our findings. The authors suggested that by focusing on criminal convictions we may have been studying a very select and unrepresentative subgroup of the population and that, "It is unclear whether they would have found similar effects in the same cohort had they examined other psychiatric, behavioral, or developmental outcomes."1 We especially want to clarify this point because our research group and others have, in fact, published numerous studies on SDP using quasi-experimental designs. In addition to predicting convictions, our article2 also included sensitivity analyses on a reliable and valid psychiatric assessment of all males in the country. And, our research group has published numerous studies on the same cohort, examining the association between SDP and intellectual abilities,6 academic achievement and school grades,7 and stress reactivity,8 to name just a few examples. Plus, sibling comparison and other quasi-experimental studies have been conducted in numerous populations and have assessed other behavioral and cognitive domains.9 Each study drew the same conclusion--familial factors and not the specific effects of SDP on the developing fetus account for the associations between SDP and each measure of behavioral, social, and cognitive functioning. The interpretation of our results in the article published in Archives,2 consequently, cannot be attributable solely to the prediction of a small/unrepresentative subgroup of individuals; rather, our conclusions are supported by every quasi- experimental study of SDP and behavioral and cognitive traits.
Our research, as well as the work by many other groups, strongly suggests that prevention/intervention programs must also target the multiple risk factors that co-occur with maternal SDP. And, yes, more research needs to be conducted. Does SDP cause other behavioral and substance use outcomes? If not, what are the true causal risk factors? But, to paraphrase our colleagues in the field, researchers studying SDP must be wary of causal claims.10
References
1. Talati A, Weissman MM. In utero smoking exposure warrants further investigation. Archives of General Psychiatry. 2010;67:1094.
2. D'Onofrio BM, Singh AL, Iliadou A, et al. Familial confounding of the association between maternal smoking during pregnancy and offspring criminality: A population-based study in Sweden. Archives of General Psychiatry. 2010;67:529-538.
3. Cnattingius S. The epidemiology of smoking during pregnancy: Smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine and Tobacco Research. 2004;6:S125-S140.
4. British Academy of Science Working Group. Social science and family policy. London: British Academy Policy Center; 2010.
5. Academy of Medical Sciences Working Group. Identifying the Environmental Causes of Disease: How Should We Decide What to Believe and When to Take Action?: Academy of Medical Sciences; 2007.
6. Lundberg F, Cnattingius S, D’Onofrio B, et al. Maternal smoking during pregnancy and intellectual performance in young adult Swedish male offspring. Pediatric and Perinatal Epidemiology. 2010;24:79-87.
7. D'Onofrio BM, Singh AL, Iliadou A, et al. A quasi-experimental study of maternal smoking during pregnancy and offspring academic achievement. Child Development. 2010;81:80-100.
8. Kuja-Halkola R, D’Onofrio BM, Illiadou A, Pawitan Y, Langstrom N, Lichtenstein P. Prenatal smoking exposure and stress coping in late adolescence: No causal link. International Journal of Epidemiology. in press.
9. Knopik VS. Maternal smoking during pregnancy and child outcomes: Real or spurious effect? Developmental Neuropsychology. 2009;34:1-36.
10. Thapar A, Rutter M. Do prenatal risk factors cause psychiatric disorder? Be wary of causal claims. British Journal of Psychiatry. 2009;195:100-101.

Conflict of Interest: Financial Disclosure: There are no conflicts of interest.
Funding: This work is supported in part by grant R01 HD061817 (Quasi-Experimental Studies of Early Risk Factors for Severe Psychopathology) and R01 HD061384 (Early Causal Risk FActors for Delinquency: Quasi Experimental Tests), as well as funds from the Swedish Research Council: Medicine, Swedish Prohibition Service, and the Karolinska Institutet.