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.

中文翻译：

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母亲怀孕期间吸烟与后代骨折：基于国家登记的兄弟姐妹比较研究。


目的 研究母亲孕期吸烟对后代不同发育阶段骨折的影响。设计基于国家登记的出生队列研究，采用兄弟姐妹比较设计。设置瑞典。参与者 1 680 307 名出生于 1983 年至 2000 年间瑞典的女性在怀孕早期吸烟（n=377 367，22.5%）和不吸烟（n=1 302 940）。随访截止至 2014 年 12 月 31 日。主要观察指标为 32 岁以下的骨折情况。结果 在中位随访 21.1 年期间，观察到 377 970 例骨折（按出生年份标准化的骨折总发病率为每 1000 人年 11.8 例）。母亲怀孕期间吸烟与后代骨折风险之间的关联因年龄而异。在整个队列中，母亲吸烟与后代 1 岁之前较高的骨折率相关（出生年份标准化骨折率，接触和未接触母亲吸烟的儿童分别为每 1000 人年 1.59 例和 1.28 例）。调整潜在混杂因素后，母亲吸烟与不吸烟相比的风险比为 1.27（95% 置信区间为 1.12 至 1.45）。这种关联遵循剂量依赖性模式（与不吸烟相比，每天吸 1-9 支香烟和每天≥10 支香烟的风险比分别为 1.20（95% 置信区间 1.03 至 1.39）和 1.41（1.18 至 1.69））尽管置信区间更宽（与不吸烟相比，1.58（1.01 至 2.46）），但仍坚持进行同胞内比较。 在整个队列分析中，母亲怀孕期间吸烟也与 5 岁至 32 岁后代骨折发生率增加相关，但这些关联并不遵循剂量依赖性梯度。在同胞关系内分析中，通过测量和未测量的共同家族因素控制混杂，相应的点估计值全部接近零。在任何模型中，母亲吸烟与 1 至 5 岁之间的后代骨折风险均无关。结论 产前接触母亲吸烟与出生后第一年骨折发生率增加有关，但似乎对儿童后期和成年早期的骨折没有长期持久的生物学影响。