Maternal smoking during pregnancy and fractures in offspring: national register based sibling comparison study
BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.l7057 (Published 29 January 2020) Cite this as: BMJ 2020;368:l7057
- Judith S Brand, epidemiologist1 2 3,
- Ayako Hiyoshi, associate professor1 4,
- Yang Cao, associate professor1,
- Deborah A Lawlor, professor2 3,
- Sven Cnattingius, professor5,
- Scott Montgomery, professor1 5 6
- 1Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, 70185 Örebro, Sweden
- 2MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
- 3Population Health Sciences, Bristol Medical School, Bristol, UK
- 4Department of Public Health Sciences, Stockholm University, Stockholm, Sweden
- 5Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Solna, Sweden
- 6Department of Epidemiology and Public Health, University College London, London, UK
- Correspondence to: J S Brand judith.brand{at}regionorebrolan.se
- Accepted 10 December 2019
Abstract
Objective To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life.
Design National register based birth cohort study with a sibling comparison design.
Setting Sweden.
Participants 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014.
Main outcome measure Fractures by attained age up to 32 years.
Results During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and ≥10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models.
Conclusion Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.
Footnotes
Contributors JSB and SM conceived and designed the study. DAL and SC assisted with the methods. JSB did the data analysis. JSB and SM drafted the initial manuscript. All authors assisted with interpretation, commented on drafts of the manuscript, and approved the final version. JSB is the guarantor and attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding: This work was supported by the Örebro University Hospital Research Foundation Nyckelfonden (OLL-695391) and by the UK Economic and Social Research Council as a grant to the International Centre for Life Course Studies (ES/JO19119/1). DAL’s contribution to this work was supported by the UK Medical Research Council (MC_UU_00011/6) and National Institute for Health Research (NF-0616-10102). The funders had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from Örebro University Hospital Research Foundation Nyckelfonden (OLL-695391) and the UK Economic and Social Research Council as a grant to the International Centre for Life Course Studies (ES/JO19119/1); DAL’s contribution to this work was supported by the UK Medical Research Council (MC_UU_00011/6) and National Institute for Health Research (NF-0616-10102); no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by the Swedish Ethical Review Authority (reference No 2019-04143)
Data sharing: No additional data available. For statistical coding relating to analysis of the data, contact the corresponding author at judith.brand{at}regionorebrolan.se.
The lead author (JSB) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Dissemination to participants and related patient and public communities: There are no plans to directly disseminate the results of the research to study participants. The dissemination to the Swedish population (which constitutes the study population) and the broader public will be achieved through media outreach (ie, press release and publication in popular media).
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