Maternal Snuff Use and Smoking and the Risk of Oral Cleft Malformations - A Population-Based Cohort Study
Open accessAbstract
OBJECTIVE: To determine if maternal use of snuff (containing high levels of nicotine, low levels of nitrosamines and no combustion products) is associated with an increased risk of oral cleft malformations in the infant and whether cessation of snuff use or smoking before the antenatal booking influences the risk. METHOD: A population-based cohort study was conducted on all live born infants, recorded in the Swedish Medical Birth Register from 1999 through 2009 (n = 1 086 213). Risks of oral clefts were evaluated by multivariate logistic regression analyses (using adjusted odds ratios, with 95% confidence intervals [CI]). RESULTS: Among 975 866 infants that had information on maternal tobacco use, 1761 cases of oral clefts were diagnosed. More than 50% of the mothers who used snuff or smoked three months prior pregnancy stopped using before the antenatal booking. Almost 8% of the mothers were smoking at the antenatal booking and 1,1% of the mothers used snuff. Compared with infants of non-tobacco users, the adjusted odds ratios (95% CI) of any oral cleft for infants of mothers who continued to use snuff or to smoke were 1.48 [1.00-2.21] and 1.19 [1.01-1.41], respectively. In contrast, in infants of mothers who stopped using snuff or stopped smoking before the antenatal booking, the corresponding risks were not increased (adjusted odds ratios [95% CI] were 0.71 [0.44-1.14] and 0.88 [0.73-1.05], respectively). CONCLUSION: Maternal snuff use or smoking in early pregnancy is associated with an increased risk of oral clefts. Infants of mothers who stopped using snuff or stopped smoking before the antenatal booking had no increased risk of oral cleft malformations. Oral snuff or other sources of nicotine should not be recommended as an alternative for smoke-cessation during pregnancy.
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Smokeless tobacco use during pregnancy is associated with preterm birth, stillbirth, and orofacial clefts.
“These studies have found associations with preterm birth, stillbirth, and orofacial cleft defects”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [35]
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“Exposure to various pharmacological medications, nicotine, or alcohol increases incidence of cleft palate suggesting that palate development is especially susceptible to genetic and environmental insult.(5-11) Children with cleft palate have difficulty with feeding, speech, and hearing.”
BackgroundOzekin, Y. H., Saal, M. L., Pineda, R., Moehn, K. M., Ordonez-Erives, M. A., Figueroa, M. F. D., Frazier, C., Korth, K. M., Königshoff, M., Bates, E. A., et al. (2023) · Developmental Biology · doi:10.1016/j.ydbio.2023.06.002 · Cited by 19 · see citing works
Nordenstam, F., Lundell, B. P. W., Bonamy, A. E., Raaschou, P., & Wickström, R. (2018) · Acta Paediatrica · doi:10.1111/apa.14602 · Cited by 17 · see citing works
Self-citationKreyberg, I., Nordhagen, L. S., Bains, K. E. S., Alexander, J., Becher, R., Carlsen, K. H., Glavin, K., & Carlsen, K. C. L. (2019) · Acta Paediatrica · doi:10.1111/apa.14737 · Cited by 17 · see citing works
“2014 (14) Associated with increased risk oral cleft malformation (OR 1.”
BackgroundTang, M., Wang, Y., Han, S., Guo, S., & Wang, D. (2014) · Genetic Testing and Molecular Biomarkers · doi:10.1089/gtmb.2014.0056 · Cited by 14 · see citing works
“Exposure to environmental risk factors during early pregnancy, including smoking, drinking, lack of vitamins, and viral infection, may be strongly associated with the risk of NSCL/P (Jia et al. , 2011a; Gunnerbeck et al. , 2014).”
Lundholm, C., Gunnerbeck, A., D'Onofrio, B. M., Larsson, H., Pershagen, G., & Almqvist, C. (2020) · Clinical & Experimental Allergy · doi:10.1111/cea.13593 · Cited by 13 · see citing works
Self-citationOginawati, K., Susetyo, S. H., Cahyani, Z. N., & Fahimah, N. (2022) · Environmental Science and Pollution Research · doi:10.1007/s11356-022-21611-1 · Cited by 12 · see citing works
“2018), exposure to cigarette smoke (Gunnerbeck et al. 2014), alcohol consumption (DeRoo et al.”
BackgroundUse of snus and smoking tobacco among pregnant women in the Agder counties
Rygh, E., Gallefoss, F., & Reiso, H. (2016) · Tidsskrift for Den norske legeforening · doi:10.4045/tidsskr.15.1341 · Cited by 11 · see citing works
Wang, B.-Q., Gao, S.-T., Chen, K., Xu, Z., Sun, J., Xia, Y. F., & Lv, Z. (2018) · Bioscience Reports · doi:10.1042/bsr20181676 · Cited by 11 · see citing works
Maternal snuff use and cotinine in late pregnancy—A validation study
Gunnerbeck, A., Raaschou, P., Cnattingius, S., Bonamy, A. E., & Wickström, R. (2018) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.13410 · Cited by 11 · see citing works
Self-citationByberg, K. K., Lundholm, C., Brew, B. K., Rejnö, G., & Almqvist, C. (2021) · International Journal of Epidemiology · doi:10.1093/ije/dyab204 · Cited by 9 · see citing works
Study of the elemental composition of saliva of smokers and nonsmokers by X-ray fluorescence
Poles, A. A., Balcão, V. M., Chaud, M. V., Vila, M. M. D. C., Aranha, N., Hanai‐Yoshida, V. M., & de Oliveira, J. M. (2016) · Applied Radiation and Isotopes · doi:10.1016/j.apradiso.2016.09.007 · Cited by 8 · see citing works
“It is believed that more than a thousand components of carcinogens and toxic gases and metals (Gunnerbeck et al., 2014) are present in tobacco.”
BackgroundIs there an association between maternal smoking and oral clefts?
Crossan, E., & Duane, B. G. (2018) · Evidence-Based Dentistry · doi:10.1038/sj.ebd.6401292 · Cited by 8 · see citing works
Snus in pregnancy and infant birth size: a mother–child birth cohort study
Kreyberg, I., Hilde, K., Bains, K. E. S., Carlsen, K., Granum, B. B., Haugen, G. N., Hedlin, G., Jonassen, C. M., Nordhagen, L. S., Nordlund, B., et al. (2019) · ERJ Open Research · doi:10.1183/23120541.00255-2019 · Cited by 7 · see citing works
Acute exposure to electronic cigarette components alters mRNA expression of pre‐osteoblasts
Dabdoub, S. M., Greenlee, A. N., Abboud, G., Brengartner, L., Zuiker, E., Gorr, M. W., Wold, L. E., Kumar, P., & Cray, J. (2024) · The FASEB Journal · doi:10.1096/fj.202302014rrr · Cited by 6 · see citing works
“55,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79 This gap is compounded by rising exposures driven by a misleading perception of safety for ENDS use compared to tobacco products; primarily driven by industry advertising.”
Turner, J., Garratt, D., Barwick, A., McLindon, L. A., Spark, M. J., & Smith, A. (2024) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3392 · Cited by 6 · see citing works
“45,46 A number of the congenital anomalies encountered in this review can be explained by circumstances other than exposure to mifepristone.”
Lei, W., Xia, Y., Wu, Y., Fu, G., & Ren, A. (2018) · Genetic Testing and Molecular Biomarkers · doi:10.1089/gtmb.2018.0037 · Cited by 6 · see citing works
Maternal Smoking Leads to Larger Cleft Palate Defects
Lacerda, R. H. W., Furtado, P. G. C., & Vieira, A. R. (2021) · Frontiers in Dental Medicine · doi:10.3389/fdmed.2020.632037 · Cited by 5 · see citing works
OROFACIAL CLEFTS AND CARDIOVASCULAR RISK AND DISEASES: THE CAUSAL RELATIONSHIP AND ASSOCIATIONS.
Nwaze, C. E., Adebayo, O., Adeoye, A. M., & Akinmoladun, V. I. (2020) · PubMed Central · Cited by 3 · see citing works
Swedish smokeless tobacco and its impact on oral health: a systematic review
Jontell, M., & Bankvall, M. (2026) · Acta Odontologica Scandinavica · doi:10.2340/aos.v85.45421 · Cited by 2 · see citing works
“The finding that maternal snus use during pregnancy is associated with an increased risk of oral cleft malformations in offspring is of considerable concern [32].”
InfluentialIn utero exposure to electronic cigarette carriers alters craniofacial morphology
Richlak, E., Shope, L., Leonard, E., Sewell, L., Maykovich, T., Mohi, A., Miller, R. A., Gorr, M. W., Wold, L. E., & Cray, J. (2025) · PLoS ONE · doi:10.1371/journal.pone.0327190 · Cited by 2 · see citing works
Smokeless Tobacco - Health Hazards or Less Harm?
Bolinder, G., & Gilljam, H. (2015) · Progress in respiratory research/Progress in research in emphysema and chronic bronchitis/Progress in respiration research · doi:10.1159/000369503 · Cited by 2 · see citing works
Maternal smoking during pregnancy - Long-term health effects in the offspring
Mattsson, K. (2015) · Lund University Publications (Lund University) · Cited by 2 · see citing works
Paludetto, R., & Raimondi, F. (2012) · Springer eBooks · doi:10.1007/978-88-470-1405-3_54 · Cited by 1 · see citing works
“More recently, maternal snuff use in pregnancy (a source of nicotine containing low levels of nitrosamines and no combustion products) has been associated with the same increased risk of oral clefts as tobacco smoking (Gunnerbeck et al. 2014).”
BackgroundPaludetto, R., Capasso, L., & Raimondi, F. (2016) · Springer eBooks · doi:10.1007/978-3-319-18159-2_194-1 · Cited by 1 · see citing works
Paludetto, R., Capasso, L., & Raimondi, F. (2018) · Springer eBooks · doi:10.1007/978-3-319-29489-6_194 · Cited by 1 · see citing works
Perinatal snus exposure and cardiovascular function in the child
Nordenstam, F. (2019) · Figshare · Cited by 1 · see citing works
The neurotoxic effects of prenatal nicotine exposure may impair breastfeeding
Gunnerbeck, A. (2019) · Acta Paediatrica · doi:10.1111/apa.14854 · Cited by 1 · see citing works
Self-citationAn Evaluation of Competing Risks in Studies of Perinatal Mortality and Birth Defects
Heinke, D. (2018) · Digital Access to Scholarship at Harvard (DASH) (Harvard University) · Cited by 1 · see citing works
E-cigarettes and youth: a major Public Health concernPreprint
Virgili, F., Nenna, R., David, S. B., Mancino, E., Mattia, G. D., Matera, L., Petrarca, L., & Midulla, F. (2021) · doi:10.22541/au.162526966.60449161/v1 · Cited by 1 · see citing works
Effekter i munnhulen ved bruk av snus
Rukke, H. V., Kopperud, S. E., & Becher, R. (2016) · Aktuel nordisk odontologi · doi:10.18261/issn2058-7538-2016-01-12
Ein In-vitro-Mausmodell für die Palatogenese und die Entstehung von Gaumenspalten
den Hoff, J. W. V., Fuentes, L. R., Bloemen, M., & Kuijpers‐Jagtman, A. M. (2017) · Informationen aus Orthodontie & Kieferorthopädie · doi:10.1055/s-0043-109044
“Dies erklärt möglicherweise den Zusammenhang zwischen Rauchen und dem Risiko zur Entstehung von Spalten beim ungeborenen Kind [23].”
BackgroundInfluentialLundholm, C. (2021) · Figshare
The use of nicotine products and effects of snus in pregnancy
Kreyberg, I. (2021) · NORA - Norwegian Open Research Archives
Use of Nicotine-Containing Products During Pregnancy: Effects on Fetal Development
Chun, J. (2024) · International STEAM Communications · doi:10.37906/isteamc.2024.1
Ramamoorthy, S., Kumar, I. S. C., Mangla, M., Jyothi, V. L. N., Sellamuthu, P., Kondapuram, N., Tikka, S. K., Ramamurthy, D., & Eerike, M. (2026) · Substance Use & Addiction Journal · doi:10.1177/29767342261421818
Consequences of Fetal Substance Exposure
Castro, R., Shaw, G. M., & Cohen, R. S. (2026) · Cambridge University Press eBooks · doi:10.1017/9781009418034.013
- Authors
- Gunnerbeck, A., Edstedt Bonamy, A.-K., Wikström, A.-K., Granath, F., Wickström, R., & Cnattingius, S.
- Affiliations
- Karolinska University Hospital (SE)
- Uppsala University (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Gunnerbeck, Anna
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-01-15
- Volume
- 9
- Issue
- 1
- Pages
- e84715
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3893163
- OpenAlex
- W2077151114
- Cited by
- 58
- References
- 51
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 10 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 1 · 2012: 1
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Forskningsrådet för Arbetsliv och Socialvetenskap
- Karolinska Institutet
- Stockholms Läns Landsting
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Cleft Lip and Palate Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- orofacial clefts, maternal smoking, prenatal tobacco exposure, nicotine, nitrosamines, antenatal booking, congenital malformations
- MeSH terms
- Cleft Lip, Cleft Palate, Female, Humans, Infant, Newborn, Risk Factors, Smoking, Tobacco, Smokeless, Cohort Studies
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