Maternal Smoking During Pregnancy and Childhood Obesity: linear association or threshold effect? An IPD Meta-Analysis

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In a recent state of the art paper Gillman MW and Ludwig DS (NEJM, 2013) suggested that 7% of the probability of obesity at 7 to 10 years of age could be explained by maternal smoking in pregnancy. This empirical evidence for a causal association between intrauterine exposure to nicotine and overweight in the offspring has been questioned, however, because of potential residual confounding. Major concerns regarding possible residual confounding were based on the observation that children who were exposed to paternal or second-hand smoking while in utero or after pregnancy also had an increased risk of being overweight, although smaller than for maternal smoking. Is this a reflection of a linear dose effect relation? Or are both effects are reflection of residual confounding by unknown family factors? A linear dose effect relation might appear possible in face of some overlap in cotinine concentrations in the newborns hair between newborns exposed to maternal or paternal smoking in pregnancy. The reported data on the dose effect of maternal smoking in pregnancy are equivocal, however: some suggesting a threshold effect with a steep increase related to small doses while others suggest a linear association. These equivocal findings may reflect artefacts due to reporting effects by dose categories. The original data of most studies, however, ascertained maternal smoking exposure by number of cigarettes smoked. An IPD meta-analysis of these data will therefore allow to elucidate the true nature of the dose effect of maternal smoking in pregnancy. The authors of 16 studies have expressed their interest in a collaborative IPD study allowing to study the association in more than 300 000 mother infant pairs. These data will provide a clue for understanding potential causality of the association between maternal smoking in pregnancy and obesity in the offspring. In case of a linear association the additional effects observed for paternal smoking in pregnancy might be explained by a dose effect. In case of a threshold effect with a steep increase related to small numbers of cigarettes the effect of both maternal and paternal smoking would be more likely to reflect residual confounding related to shared family environment.