Need to Account for Familial Confounding in Systematic Review and Meta-analysis of Prenatal Tobacco Smoke Exposure and Schizophrenia

Abstract

In the context of continued uncertainty regarding the long-term mental health effects of prenatal exposure to maternal smoking during pregnancy, we read with great interest the recently published meta-analysis of smoking and schizophrenia by Hunter and colleagues.¹ Although the meta-analysis found that “exposure to prenatal smoke increased the risk of schizophrenia by 29%” (p. 3), the authors noted that “familial confounding may explain some of the observed association” (p. 8). We agree with the importance of this alternative hypothesis. In fact, we were surprised that the review did not consider the results of sibling comparison studies that have directly addressed it, particularly given that the review had the opportunity to do so using data from articles included in the meta-analysis. As we illustrate below—and as has been discussed previously²—we are concerned that limiting the focus of the review to only findings potentially subject to familial confounding rather than incorporating these sibling comparison results may lead to inaccurate inferences from the reviewed literature.