Yuan Xuefei, Zhang Fang, Lv Yan, Zhao Baohua, Zhang Hongbin, Chen Limin, Yan Hongli, Hao Xiaojiao, Dong Zhiyu
College of Life Sciences, Hebei Normal University, Shijiazhuang, China.
Center for Reproductive Medicine of Changhai Hospital, Naval Medical University, Shanghai, China.
Tob Induc Dis. 2025 Aug 1;23. doi: 10.18332/tid/207156. eCollection 2025.
This systematic review and meta-analysis aimed to quantify the dose-dependent association between tobacco exposure (active and passive smoking) and the risk of spontaneous abortion (SA), incorporating subgroup analyses to evaluate the influence of study design.
Following PRISMA guidelines, we conducted a systematic search of PubMed, Embase, and Cochrane Library databases for English-language observational studies published between 1991 and 2023. Studies were included if they reported on the association between active or passive tobacco exposure during pregnancy and SA risk (defined as pregnancy loss before 20 weeks of gestation). Studies involving induced abortion, ectopic pregnancy, or molar pregnancy were excluded. Eligible participants included pregnant women with documented smoking status. Methodological quality was assessed using MMAT, NOS, and GARD. Data were analyzed using fixed-effects or random-effects models, with heterogeneity assessed using I statistics. Interaction p-values were reported to evaluate heterogeneity between study designs.
Fourteen studies (5 cohort, 7 case-control, 2 nested case-control) with a combined sample size of 741698 pregnancies met the inclusion criteria. Active smoking was significantly associated with increased SA risk (OR=1.35; 95% CI: 1.18-1.55; I=46.8%), with the highest risk observed among individuals consuming ≥20 cigarettes/day (OR=1.45; 95% CI: 1.04-2.03). Secondhand smoke exposure also elevated SA risk (OR=1.32; 95% CI: 1.14-1.55; I=37.6%). Significant heterogeneity was observed between cohort and case-control studies (interaction p=0.001). No significant interaction was found between active and passive smoking (interaction p=0.842), but a dose-dependent interaction was observed (interaction p=0.049).
Tobacco exposure is associated with increased SA risk, particularly at higher levels. Interventions targeting heavy smokers and those exposed to secondhand smoke are needed. Limitations include imprecise smoking exposure measurement and incomplete adjustment for confounders. Future research should focus on biomarker-guided cessation strategies and explore underlying mechanisms.Systematic Review Registration: The protocol was registered in PROSPERO.ID: CRD42023406664.
本系统评价和荟萃分析旨在量化烟草暴露（主动吸烟和被动吸烟）与自然流产（SA）风险之间的剂量依赖性关联，并纳入亚组分析以评估研究设计的影响。
遵循PRISMA指南，我们对PubMed、Embase和Cochrane图书馆数据库进行了系统检索，以查找1991年至2023年发表的英文观察性研究。如果研究报告了孕期主动或被动烟草暴露与SA风险（定义为妊娠20周前流产）之间的关联，则纳入研究。涉及人工流产、异位妊娠或葡萄胎妊娠的研究被排除。符合条件的参与者包括有吸烟状况记录的孕妇。使用MMAT、NOS和GARD评估方法学质量。使用固定效应或随机效应模型分析数据，使用I统计量评估异质性。报告交互p值以评估研究设计之间的异质性。
14项研究（5项队列研究、7项病例对照研究、2项巢式病例对照研究），合并样本量为741698例妊娠，符合纳入标准。主动吸烟与SA风险增加显著相关（OR = 1.35；95%CI：1.18 - 1.55；I = 46.8%），在每天吸食≥20支香烟的个体中观察到最高风险（OR = 1.45；95%CI：1.04 - 2.03）。二手烟暴露也增加了SA风险（OR = 1.32；95%CI：1.14 - 1.55；I = 37.6%）。在队列研究和病例对照研究之间观察到显著异质性（交互p = 0.001）。主动吸烟和被动吸烟之间未发现显著交互作用（交互p = 0.842），但观察到剂量依赖性交互作用（交互p = 0.049）。
烟草暴露与SA风险增加相关，尤其是在较高水平时。需要针对重度吸烟者和二手烟暴露者的干预措施。局限性包括吸烟暴露测量不精确和混杂因素调整不完整。未来的研究应侧重于生物标志物指导的戒烟策略并探索潜在机制。系统评价注册：该方案已在PROSPERO注册。ID：CRD42023406664。
