The conventional linear regression analysis suggested that using snus during pregnancy was associated with a slight reduction in offspring birthweight (47 g), which appears to confirm the results from a previous observational analysis 
. However, the results obtained with the quasi-experimental sibling analysis showed that snus exposure during pregnancy reduces birthweight although, this reduction, is minor (20 g) and not statistically significant. The sample of siblings with contrast of exposure made it possible to reduce unaccounted confounding, but this selection also reduces the number of studied subjects and, thereby, the uncertainty of the estimates increases. However, our analysis strongly suggests that snus has a minor effect on birthweight reduction and, therefore, that nicotine does not seem to be the main mechanism involved in the association between smoking during pregnancy and birthweight. This result is in line with a previous conventional analysis that did not find an association between nicotine replacement therapy (i.e., patch, gum, inhaler), or other types of smokeless tobacco (i.e., iqmik, commercial chew) and offspring birthweight, 
Our findings should not be interpreted as suggesting that the use of snus is a healthier alternative to smoking during pregnancy because snus also has harmful health consequences 
and it has been found to be addictive 
. In fact, previous perinatal studies have found that snus is associated with stillbirth, preeclampsia, and very preterm and preterm babies 
, although the causal strength of those observations remains to be confirmed. Our study contributes to the ongoing debate 
on the health implications of using snus.
Our results, moreover, are of particular importance to identifying the mechanisms through which tobacco consumption may influence birthweight because this knowledge is necessary for planning effective therapeutic interventions 
. Using a quasi-experimental sibling analysis, our study supports the hypothesis that the adverse effect of smoking during pregnancy in birthweight reduction is not mediated by nicotine but rather related to toxic products from the tobacco combustion or other smoking constituents. Cigarette smoke contains not only carbon monoxide, a well-known poisonous product of combustion 
, but also such chemical substances as carcinogens, toxic heavy metals, and many other elements of untested toxicity 
. Moreover, cigarette smoke facilitates nicotine absorption when the smoke reaches the small airways and alveoli of the lung, since only small amounts of nicotine are absorbed through the buccal mucosa 
. In other words, smoking includes toxic mechanisms that are absent in smokeless tobacco.
In addition to the quasi-experimental approach, the current study has a number of other strengths. Our analyses are based on a nationwide birth registry covering nearly 99% of the deliveries occurring in Sweden 
. This dataset contains information on snus use at two moments during pregnancy (first and third trimester). This allowed us to identify siblings discordant in exposure to snus, and to distinguish between mothers with different patterns of snus use. Moreover, we were able to control for variables which vary between pregnancies (such as gestational age, birth order and maternal age). These adjustments are essential since the strength of the sibling analyses is based on constant environmental factors and genetic background 
However, our investigation also has several limitations. The self-reported information on snus use by the mothers may be inaccurate, which may lead to information bias towards the null. For instance, if a true snus user only reported using snus in one pregnancy but not in the other (creating false contrast of exposure), the association between maternal snus use and birthweight will become attenuated 
. Nevertheless, a study performed in Sweden comparing self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy concluded that self-reported information on nicotine exposure had acceptable validity 
. Although this study did not validate self-reported information on snus, the societal attitude against snus is less severe than that against smoking, which might promote more accurate self-reporting of snus habits than of smoking habits. Moreover, the fact that we had information on snus use during two moments during pregnancy may increase our probability of identifying true snus users than if we only had one observation.
Additionally, we used a sibling analysis to account for unmeasured maternal confounders, but other temporal confounders may exist that were not considered. Moreover, the siblings were only matched by their mothers. At the time of our investigation, we did not have information about the father and, therefore, some of the siblings may have only been half siblings. Moreover, it is possible that the association between SDP and birthweight is confounded by smoking in the father, influencing the child through passive smoking in the mother or smoke exposure among those who do not smoke or quit.
In spite of the fact that we use a population register that contains all deliveries in Sweden for a period of eight years, we were not able to study other outcomes derived from birthweight such as low birthweight (<2,500 g) or small-for-gestational-age, the last of which has been recently explored through a conventional analysis 
, because the sibling analysis for dichotomous outcomes restricts the sample considerably and, therefore, it does not allow us to reach any conclusion.
In summary, applying a quasi-experimental sibling design to a large database with detailed information on tobacco use, we observed that snus exposure during pregnancy has a minor effect on birthweight reduction. More empirical evidence is required to confirm this result, especially with a larger sibling sample. Nevertheless, our results suggest that the adverse effect of smoking during pregnancy on offspring birthweight may be explained by the combustion or other products of smoking rather than by nicotine.