The authors have declared that no competing interests exist.
Conceived and designed the experiments: SJ JM. Performed the experiments: SJ JM. Analyzed the data: SJ. Contributed reagents/materials/analysis tools: SJ JM. Wrote the paper: SJ JM.
Current observational evidence indicates that maternal smoking during pregnancy is associated with reduced birthweight in offspring. However, less is known about the effect of smokeless tobacco on birthweight and about the possible mechanisms involved in this relationship. This paper studies the effect of Swedish smokeless tobacco (snus) on offspring birthweight comparing the results obtained from a conventional linear regression analysis and from a quasi-experimental sibling design using a multilevel linear regression analysis. From the Swedish Medical Birth Register, we investigated 604,804 singletons born between 2002 and 2010. From them, we isolated 8,861 siblings from 4,104 mothers with discrepant snus-use habits (i.e., women who had at least one pregnancy during which they used snus and at least one other pregnancy in which they did not). The conventional analysis shows that continuous snus use throughout the pregnancy reduces birthweight in 47 g while quitting or relapsing snus has a minor and statistically non-significant effect (−6 g and −4 g, respectively). However, using a sibling analysis the effect observed for mothers who continue to use snus during pregnancy is less intense than that observed with previous conventional analyses (−20 g), and this effect is not statistically significant. Sibling analysis shows that quitting or relapsing snus use after the first trimester slightly reduces birthweight (14 g).However, this small change is not statistically significant. The sibling analysis provides strong causal evidence indicating that exposure to snus during pregnancy has a minor effect on birthweight reduction. Our findings provide a new piece of causal evidence concerning the effect of tobacco on birthweight and support the hypothesis that the harmful effect of smoking on birthweight is not mainly due to nicotine.
Maternal smoking during pregnancy is considered the most important preventable risk factor on offspring birthweight reduction
Our aim is to study the effect of smokeless tobacco (Swedish “snus”) during pregnancy on offspring birthweight. Swedish snus differs from other types of snuff products as it contains lower levels of harmful substances
A Swedish study showed that snus is associated to birthweight reduction
The database used in our study was constructed by the National Board of Health and Welfare in coordination with Statistics Sweden, and it was approved by the Regional Ethical Review Board in Southern Sweden. Lund University signed a contract of confidentiality with Swedish Authorities; however, in the data we analyzed, the identification numbers were replaced with arbitrary numbers to safeguard the anonymity of the subjects. Active informed consent was waived as a requirement for the construction of the database.
We based our study on the Swedish Medical Birth Register (MBR), which contains approximately 99% of all deliveries occurring in the country
Thereafter, we selected a subsample of siblings with discordant snus-use habits between pregnancies i.e., women who had at least one pregnancy during which they used snus (either in the 1st and/or 3rd trimester) and at least another pregnancy during which they did not use snus in any of the trimesters (reference). This procedure rendered 8,861 discordant siblings and 4,104 mothers. With this sample we performed the corresponding sibling analysis.
The study outcome variable was birthweight in grams (g). Information on snus use during pregnancy was self-reported and assessed at the first antenatal visit (i.e., between gestational weeks 10 and 12) and in the third trimester (i.e., gestational weeks 30–32) using a questionnaire administered by the midwife. We distinguished between the following: (i) non-users of snus during pregnancy (i.e., those who report using non-use of snus in the first and in the third trimester); (ii) continuous snus use during pregnancy (i.e., those who report using snus in the first and in the third trimester), (iii) quitting snus use (i.e., those who report using snus in the first trimester but non-use in the third trimester); (iv) relapsing snus use (i.e., those who report non-snus use in the first trimester but snus use in the third trimester). We completed this variable including all possible combinations between snus use information and missing data in the two periods (first and third trimester). Thus, we also included (v) “missing”–“snus use” (i.e., those who have “missing” in the first trimester but reported snus use in the third trimester), (vi) “snus use”–“missing” (i.e., those who report snus use in the first trimester and missing in the third trimester), (vii) “missing”–“non-use” (i.e., those with missing snus use in the first trimester and who reported snus use in the third trimester), (viii) “non-snus”–“missing” (i.e., those who reported snus use in the first trimester and missing in the third trimester) and (ix) “missing”– “missing” (i.e., those who did not report information on snus use at any trimester). Categories (vii) and (viii), as we said above, were finally excluded because of the small number of cases.
We adjusted all models for gestational age, birth order, sex, mother’s age, and marital status (see
Full sample | % | Sibling sample % | ||
Never used snus |
591,690 | 97.83 | 4,641 | 52.38 |
Continous snus use | 2,298 | 0.38 | 455 | 5.13 |
Quit snus use | 4,934 | 0.82 | 1,739 | 19.63 |
Snus use relapse | 1,107 | 0.18 | 424 | 4.79 |
No use snus -missing | 3,313 | 0.55 | 1,168 | 13.18 |
Snus use -missing | 1,462 | 0.24 | 434 | 4.90 |
<20 | 12,229 | 2.02 | 248 | 2.80 |
20–24 | 54,793 | 9.06 | 1,117 | 12.61 |
25–34 |
411,113 | 67.97 | 6,087 | 68.69 |
35–40 | 125,972 | 20.83 | 1,403 | 15.83 |
>40 | 668 | 0.11 | 5 | 0.06 |
Missing | 29 | 0.00 | 1 | 0.01 |
Cohabiting with father |
577,942 | 95.56 | 8,427 | 95.10 |
Single | 5,750 | 0.95 | 71 | 0.80 |
Other family situation | 15,784 | 2.61 | 272 | 3.07 |
Missing | 5,328 | 0.88 | 91 | 1.03 |
1 |
275,670 | 45.58 | 3,342 | 37.72 |
2 | 230,225 | 38.07 | 3,833 | 43.26 |
3 | 75,532 | 12.49 | 1,184 | 13.36 |
>4 | 23,377 | 3.87 | 502 | 5.67 |
Female |
293,890 | 48.59 | 4,386 | 49.50 |
Male | 310,914 | 51.41 | 4,475 | 50.50 |
3599 (604,804; 545) | 3647 (8,861; 517) |
Reference category in the analyses.
We applied a conventional multiple linear regression analysis to estimate the association between maternal SDP and offspring birthweight for the full sample in order to replicate the common standard procedure, which generally violates the assumption of independence between the observations by including siblings without special treatment. Thereafter, following Iliadou et al’s approach
The socio-demographic and clinical characteristics of the full sample and the subpopulation of siblings are presented in
Conventional analysis | Sibling analysis | |||||
Categories of snus use | N (%) | β | CI-95% | N (%) | β | CI-95% |
Never used snus (Reference/intercept) | 591,690 (97.83) | 3581 | [3579 3583] | 4,641 (52.38) | 3615 | [3597 3632] |
Continous snus use | 2,298 (0.38) | −47 | [−63 −47] | 455 (5.13) | −20 | [−52 12] |
Quitting snus use | 4,934 (0.82) | −6 | [−17 4] | 1,739 (19.63) | −14 | [−31 3] |
Snus use relapse | 1,107 (0.18) | −4 | [−27 19] | 424 (4.79) | −14 | [−46 18] |
No snus use-missing | 3,313 (0.55) | 33 | [20 47] | 1,168 (13.18) | 4 | [−16 24] |
Snus use-missing | 1,462 (0.24) | −25 | [−45 −5] | 434 (4.9) | −33 | [−66 −0.08] |
All models were adjusted for gestational age, marital status, maternal age, birth order, sex of the newborn.
There were no statistically significant differences in the quasi-experimental sibling analysis when comparing any amount of snus use with no snus use in any of the categories but in the category “snus use”–“missing” (33 g.). Similar results are found when using the exposure variable as dichotomy (never use snus/any snus use) so the uncertainty does not depend on the disaggregation of the snus use exposure (data not shown in tables). Compared to never used snus (reference), mothers who use snus in any trimester have lighter babies on average (−19; 95%CI −27; −11) based on the conventional analysis while no statistical differences are observed with the sibling analysis −12; 95%CI −25; 2).
Snus use during pregnancy | 1st study pregnancy | 2nd study pregnancy | |||||
1st | 2nd | N | Mean Birthweight (SD) | Adjusted Birthweight (95% CI) | N | MeanBirthweight(SD) | Adjusted Birthweight (95% CI) |
No | No | 140,761 | 3608 (534) | Reference | 140,761 | 3609 (532) | Reference |
Yes | No | 1,277 | 3628 (522) | 4 [−21 30] | 1,277 | 3630 (499) | 12 [−14 37] |
No | Yes | 1,253 | 3617 (520) | −9 [−35 16] | 1,253 | 3629 (558) | 23 [−2 49] |
Yes | Yes | 726 | 3580 (547) | −41 [−74 −7] | 726 | 3572 (527) | −56 [−90 −22] |
All models were adjusted for gestational age, marital status, maternal age, birth order, sex of the newborn.
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
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
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
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
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
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
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.