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Cited by 22Prenatal Substance Exposure EffectsSmoking Behavior and CessationMaternal and Neonatal Healthcare

The effect of swedish snuff (snus) on offspring birthweight: a sibling analysis

Open access
Juárez, Sol Pía, Merlo, Juan·2013·PLoS ONE
DOI 10.1371/journal.pone.0065611PMC PMC3680479
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Abstract

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.

AI snapshot

Written from the paper’s full text.

TL;DR

In a Swedish Medical Birth Register study, conventional regression linked continuous snus use during pregnancy to a 47 g birthweight reduction, but a quasi-experimental sibling analysis found only a minor, non-significant reduction (−20 g). The authors conclude that snus exposure has little effect on birthweight and that nicotine is unlikely to be the main mechanism by which smoking reduces birthweight.

Key findings

  • Conventional multiple linear regression showed continuous snus use throughout pregnancy was associated with a 47 g lower birthweight; quitting and relapsing snus had minor, non-significant effects (−6 g and −4 g, respectively).
  • In the sibling analysis, continuous snus use was associated with a −20 g difference (95% CI −52 to 12), which was not statistically significant; quitting (−14 g; 95% CI −31 to 3) and relapsing (−14 g; 95% CI −46 to 18) were also non-significant.
  • With any snus use as a dichotomy, the conventional analysis showed −19 g (95% CI −27 to −11), while the sibling analysis showed −12 g (95% CI −25 to 2).
  • Among 144,017 mothers with two subsequent births, only continued snus use in both pregnancies showed a statistically significant birthweight reduction: −41 g in the first study pregnancy and −56 g in the second.

Methods

  • Data came from the Swedish Medical Birth Register for 2002–2010: 604,804 singletons after exclusions for the conventional analysis, and a sibling subsample of 8,861 siblings from 4,104 mothers with discordant snus-use habits across pregnancies.
  • The study compared conventional multiple linear regression with a quasi-experimental sibling design using multilevel linear regression (siblings nested within mothers), Markov Chain Monte Carlo estimation, and orthogonal parameterization; models adjusted for gestational age, birth order, sex, maternal age, and marital status.
  • A separate analysis compared birthweight differences in two subsequent pregnancies among 144,017 mothers with two births.

Limitations

  • The paper states that self-reported snus use may be inaccurate, potentially biasing results toward the null; sibling analysis accounts for unmeasured maternal confounders but not temporal confounders.
  • The paper notes siblings were matched only by mothers, father information was unavailable, some siblings may have been half-siblings, and paternal smoking/passive smoke exposure could confound results.
  • The paper states it could not study low birthweight (<2,500 g) or small-for-gestational-age because sibling analysis for dichotomous outcomes restricts the sample considerably; the text also makes evident that the sibling sample is much smaller, increasing uncertainty in estimates.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0065611

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 18 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the conventional analysis, continuous snus use throughout pregnancy reduces birthweight by 47 g.

    “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).”
    • Also stated in: § Results · plain
      “We observed a birthweight reduction for those who used snus throughout the whole pregnancy (i.e., 47 g) those who quit after the first prenatal visit (14 g), and those who relapsed after the first trimester (14 g).”
    • Also stated in: § Results · plain
      “| Continous snus use | 2,298 (0.38) | −47 | [−63 −47] | 455 (5.13) | −20 | [−52 12] |”
    Quote in the paperSubstantial claim
  • Findingown data

    In the conventional analysis, any snus use in any trimester is associated with a birthweight reduction of 19 g (95% CI −27 to −11) compared with never use.

    “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).”
    Quote in the paperSubstantial claim
  • Findingown data

    In the conventional analysis, quitting snus use has a minor and statistically non-significant effect of −6 g on birthweight.

    “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).”
    Quote in the paperSubstantial claim
  • Findingown data

    In the sibling analysis, the 'snus use'-'missing' category showed a statistically significant birthweight reduction of 33 g compared with never users.

    “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.).”
    • Also stated in: § Results · plain
      “| Snus use-missing | 1,462 (0.24) | −25 | [−45 −5] | 434 (4.9) | −33 | [−66 −0.08] |”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the conventional analysis, relapsing snus use has a minor and statistically non-significant effect of −4 g on birthweight.

    “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).”
    Quote in the paperSubstantial claim
  • May combine two claims. 8
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Findingown data

    In the sibling analysis, any snus use in any trimester is associated with a birthweight difference of −12 g (95% CI −25 to 2), which is not statistically significant.

    “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).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the sibling analysis, quitting snus use after the first trimester is associated with a birthweight reduction of 14 g, which is not statistically significant.

    “| Quitting snus use | 4,934 (0.82) | −6 | [−17 4] | 1,739 (19.63) | −14 | [−31 3] |”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the sibling analysis, relapsing snus use after the first trimester is associated with a birthweight reduction of 14 g, which is not statistically significant.

    “| Snus use relapse | 1,107 (0.18) | −4 | [−27 19] | 424 (4.79) | −14 | [−46 18] |”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In subsequent pregnancies, only mothers who used snus in both pregnancies show a statistically significant birthweight reduction; the reduction is 41 g in the first study pregnancy and 56 g in the second.

    “Only mothers who use snus in the two subsequent pregnancies show a statistically significant reduction on birthweight and, this reduction, is more intense in the second study pregnancy (56 g.) than in the first one (41 g.).”
    • Also stated in: § Results · plain
      “| Yes | Yes | 726 | 3580 (547) | −41 [−74 −7] | 726 | 3572 (527) | −56 [−90 −22] |”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the sibling analysis, continuous snus use during pregnancy is associated with a birthweight reduction of 20 g, which is not statistically significant.

    “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.”
    • Also stated in: § Discussion · plain
      “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The association between snus use during pregnancy and birthweight may be confounded by smoking in the father.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Some siblings may have only been half siblings because information about the father was not available.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    Self-reported information on snus use may be inaccurate, which may lead to information bias towards the null.

    “The self-reported information on snus use by the mothers may be inaccurate, which may lead to information bias towards the null.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] T Frisell, 2012, Sibling comparison designs: bias from non-shared confounders and measurement error, Epidemiology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Other temporal confounders may exist that were not considered.

    “Additionally, we used a sibling analysis to account for unmeasured maternal confounders, but other temporal confounders may exist that were not considered.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Products of nicotine replacement therapy do not affect birthweight reduction.

    “In human observational studies it is shown that products of nicotine replacement therapy do not affect birthweight reduction [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] TH Lassen, 2010, Maternal use of nicotine replacement therapy during pregnancy and offspring birthweight: a study within the Danish National Birth Cohort, Paediatr Perinat Epidemiol source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All models were adjusted for gestational age, birth order, sex, mother's age, and marital status.

    “We adjusted all models for gestational age, birth order, sex, mother’s age, and marital status”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A Swedish study showed that snus is associated with birthweight reduction.

    “A Swedish study showed that snus is associated to birthweight reduction [19].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] LJ England, 2003, Adverse pregnancy outcomes in snuff users, American Journal of Obstetrics and Gynecology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Maternal smoking during pregnancy is considered the most important preventable risk factor for offspring birthweight reduction.

    “Maternal smoking during pregnancy is considered the most important preventable risk factor on offspring birthweight reduction [1]–[7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1]–[7]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisereasoning

    The conventional multiple linear regression analysis generally violates the assumption of independence between observations by including siblings without special treatment.

    “which generally violates the assumption of independence between the observations by including siblings without special treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Carbon monoxide is responsible for the reduction of fetal weight in rats, while nicotine is linked to a reduction of the mother's weight gain during pregnancy.

    “In this line, a previous animal study showed that carbon monoxide is responsible for the reduction of fetal weight in rats, while nicotine linked to a reduction of the mother’s weight gain during pregnancy [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] EL Carmines, 2008, Evidence for carbon monoxide as the major factor contributing to lower fetal weights in rats exposed to cigarette smoke, Toxicol Sci source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The association between smoking during pregnancy and birthweight may be mediated by toxic products from tobacco combustion rather than by nicotine or by unmeasured familial confounding.

    “Nevertheless, other studies have shown that the offspring of passively and actively smoking mothers experience a similar birthweight reduction [10]–[13], which suggests that the association between smoking during pregnancy and birthweight may be mediated by toxic products from tobacco combustion rather than by nicotine or by unmeasured familial confounding.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10]–[13]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The offspring of passively and actively smoking mothers experience a similar birthweight reduction.

    “Nevertheless, other studies have shown that the offspring of passively and actively smoking mothers experience a similar birthweight reduction [10]–[13], which suggests that the association between smoking during pregnancy and birthweight may be mediated by toxic products from tobacco combustion rather than by nicotine or by unmeasured familial confounding.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10]–[13]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Tobacco use increases the risk of preterm deliveries.

    “Because tobacco use has been reported to increase the risk of preterm deliveries [30]–[33]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30]–[33]

      Not checked in the free run.

18 of 18

  • The paper relies on this without support.

    Less is known about the effect of smokeless tobacco on birthweight and about the possible mechanisms involved in this relationship.

    “However, less is known about the effect of smokeless tobacco on birthweight and about the possible mechanisms involved in this relationship.”

  • The paper relies on this without support.

    The association between snus use and birthweight may be confounded by familial factors linked with both snus use and birthweight.

    “However, this association may be confounded by familial factors linked with both snus use and birthweight.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Confidence interval is not centered on the reported conventional estimate

    Minor

    The conventional estimate for continuous snus use is −47 g, but the reported 95% confidence interval runs from −63 to −47 g and has a midpoint of −55 g. A conventional linear-regression confidence interval should be centered on its estimate.

    Reported -47 · recomputed -55

  • Results misstate the conventional relapse estimate

    Minor

    The Results say relapse reduced birthweight by 14 g, whereas Table 2 reports a conventional estimate of −4 g.

  • Conflicting accounts of which missing-data categories were excluded

    Minor

    The earlier exclusion statement names "missing-no snus use" and "missing-missing," corresponding to categories (vii) and (ix). The later statement instead says categories (vii) and (viii) were excluded.

  • The excluded non-snus-missing category appears in the sample tables

    Minor

    The Methods say category (viii), "non-snus"-"missing," was excluded, but Table 1 lists a "No use snus -missing" category with 3,313 observations.

  • Results misstate the conventional quitting estimate

    Minor

    The Results say quitting snus use reduced birthweight by 14 g, whereas Table 2 reports a conventional estimate of −6 g.

5 of 5

The citation lists haven’t been fetched yet

References 51 · Cited by 22

Research works printed but not linked: 1

  1. Cunningham FG (2005) Williams Obstetrics: McGraw-Hill.

Authors
Juárez, S. P., & Merlo, J.
Affiliations
Lund University (SE)
Corresponding author
Juárez, Sol Pía
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-06-12
Volume
8
Issue
6
Pages
e65611
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0065611
PMC
PMC3680479
OpenAlex
W2020406435
Cited by
22
References
51
Citations by year
2024: 3 · 2022: 5 · 2021: 2 · 2020: 2 · 2019: 3 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 1
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lund University Publications (Lund University) (submittedVersion, other-oa)
Funders
  • Forskningsrådet för Arbetsliv och Socialvetenskap (2010-0402)
  • Vetenskapsrådet (K2011-69X-15377-07-6)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Health Professions › General Health Professions › Maternal and Neonatal Healthcare
Keywords
snus, smokeless tobacco, birth weight, pregnancy, sibling comparison, causal inference, smoking during pregnancy, nicotine, Swedish Medical Birth Register
MeSH terms
Birth Weight, Female, Humans, Pregnancy, Sweden, Tobacco, Smokeless, Linear Models, Maternal Exposure, Siblings

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