Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China.
Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
Front Endocrinol (Lausanne). 2023 Jul 20;14:1193995. doi: 10.3389/fendo.2023.1193995. eCollection 2023.
BACKGROUND: The correlation between potential risk factors such as obesity (leg fat percentage (left), arm fat percentage (left), waist circumference, body fat percentage, trunk fat percentage), smoking behaviors (past tobacco smoking, smoking initiation, smoking/smokers in household, current tobacco smoking) and reproductive traits (age first had sexual intercourse (AFS), age at menarche (AAM), and age at first birth (AFB)) have been linked to the occurrence of spontaneous abortion (SA). However, the causal associations between these factors and SA remain unclear. METHODS: We conducted univariable and multivariable Mendelian randomization (MR) analyses to evaluate the associations of obesity, smoking behavior and reproductive traits with SA. To select appropriate genetic instruments, we considered those that had reached the genome-wide significance level (P < 5 × 10) in their corresponding genome-wide association studies (GWAS) involving a large number of individuals (ranging from 29,346 to 1,232,091). SA was obtained from the FinnGen consortium, which provided summary-level data for 15,073 SA cases and 135,962 non-cases. RESULTS: Assessed individually using MR, the odds ratios (ORs) of SA were 0.728 (P = 4.3608×10), 1.063 (P = 0.0321), 0.926 (P = 9.4205×10), 1.141 (P = 7.9882×10), 5.154 (P = 0.0420), 1.220 (P = 0.0350), 1.228 (P = 0.0117), 0.795 (P = 0.0056), 1.126 (P = 0.0318), for one standard deviation (SD) increase in AFS, AAM, AFB, smoking initiation, smoking/smokers in household, arm fat percentage (left), leg fat percentage (left), waist circumference and body fat percentage, 0.925 (P = 0.4158) and 1.075 (P = 0.1479) for one SD increase in past tobacco smoking, trunk fat percentage for one SD increase in SA. In multivariable MR (MVMR), only AFS (OR = 0.802; P = 0.0250), smoking initiation (OR = 1.472, P = 0.0258), waist circumference (OR = 0.813, P = 0.0220) and leg fat percentage (left) (OR = 4.446, P = 0.043) retained a robust effect. CONCLUSION: Smoking behaviors, reproductive traits and obesity-related anthropometric indicators are potential causal factors for SA. Higher leg fat percentage; smoking initiation; and lower waist circumference and AFS may increase the risk of SA. Understanding the causal relationship for SA may provide more information for SA intervention and prevention strategies.
背景：肥胖（左腿脂肪百分比、左腿臂脂肪百分比、腰围、体脂百分比、躯干脂肪百分比）、吸烟行为（过去吸烟、开始吸烟、家中吸烟/吸烟者、当前吸烟）和生殖特征（首次发生性行为年龄、初潮年龄、首次生育年龄）等潜在风险因素与自然流产（SA）的发生有关。然而，这些因素与 SA 之间的因果关系仍不清楚。
方法：我们进行了单变量和多变量孟德尔随机化（MR）分析，以评估肥胖、吸烟行为和生殖特征与 SA 的关联。为了选择合适的遗传工具，我们考虑了那些在涉及大量个体（范围从 29346 到 1232091）的全基因组关联研究（GWAS）中达到全基因组显著水平（P<5×10）的遗传工具。SA 数据来自 FinnGen 联盟，该联盟为 15073 例 SA 病例和 135962 例非病例提供了汇总水平数据。
结果：使用 MR 单独评估时，SA 的优势比（OR）分别为 0.728（P=4.3608×10）、1.063（P=0.0321）、0.926（P=9.4205×10）、1.141（P=7.9882×10）、5.154（P=0.0420）、1.220（P=0.0350）、1.228（P=0.0117）、0.795（P=0.0056）、1.126（P=0.0318），这是由于 AFS、AAM、AFB、开始吸烟、家中吸烟/吸烟者、左臂脂肪百分比（左）、左腿脂肪百分比（左）、腰围和体脂百分比各增加一个标准差所致。过去吸烟增加一个标准差的 OR 为 0.925（P=0.4158）和 1.075（P=0.1479），SA 增加一个标准差的 OR 为 1.075（P=0.1479）。在多变量 MR（MVMR）中，只有 AFS（OR=0.802；P=0.0250）、开始吸烟（OR=1.472，P=0.0258）、腰围（OR=0.813，P=0.0220）和左腿脂肪百分比（左）（OR=4.446，P=0.043）保持稳健的效应。
结论：吸烟行为、生殖特征和肥胖相关的人体测量指标可能是 SA 的潜在因果因素。较高的左腿脂肪百分比；开始吸烟；以及较低的腰围和 AFS 可能会增加 SA 的风险。了解 SA 的因果关系可能为 SA 的干预和预防策略提供更多信息。
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