Fukuda Toma, Kyozuka Hyo, Murata Tsuyoshi, Yasuda Shun, Yamaguchi Akiko, Sato Akiko, Ogata Yuka, Hosoya Mitsuaki, Yasumura Seiji, Hashimoto Koichi, Nishigori Hidekazu, Fujimori Keiya
Fukushima Regional Center for the Japan Environmental and Children's Study, Fukushima, Japan.
Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima, Japan.
J Matern Fetal Neonatal Med. 2025 Dec;38(1):2497059. doi: 10.1080/14767058.2025.2497059. Epub 2025 Apr 27.
Placental abruption is a serious complication of pregnancy, and smoking is a well-known risk factor thereof. However, evaluations of the effects of smoking mostly rely on self-reported questionnaires, resulting in incorrect representation of smoke exposure owing to incorrect reporting and missing data on passive smoking. Cotinine is a major nicotine metabolite and a sensitive biomarker in smokers. However, to date, there have been no reports on the relationship between urinary cotinine levels and onset of placental abruption. Hence, this study aimed to compare smoking status assessed using self-reports and urinary cotinine levels with placental abruption.
We analyzed data from the largest nationwide Japanese birth cohort study conducted between January 2011 and March 2014. Women with multiple pregnancies and insufficient data were excluded, leaving 82,637 women eligible for the study. Participants were classified as nonsmokers (<0.31 µg/gCr), passive smokers (0.31-36.7 µg/gCr), or active smokers (≥36.8 µg/gCr) based on comparable cutoffs for urinary cotinine levels, as reported previously. Participants were also classified as never-smokers, quitting before pregnancy, quitting after pregnancy, or current smokers according to a self-reported questionnaire. Logistic regression was used to calculate the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for the association of urinary cotinine levels and self-reported smoking status with placental abruption.
Among 82,637 participants (mean age: 31.3 years), 346 (0.42%) had placental abruption. Based on urinary cotinine-assessed smoking status, active smokers had a higher incidence of placental abruption (aOR, 1.70; 95% Cl, 1.20-2.40) than nonsmokers. In contrast, based on self-reports, there was no significant difference between current smokers and never-smokers after adjusting for established confounding factors (aOR, 1.54; 95% CI, 0.98-2.36).
Elevated urinary cotinine levels during pregnancy were significantly associated with an increased risk of placental abruption, whereas self-reported smoking status was not. Urinary cotinine levels are a more accurate and clinically reliable biomarker to assess smoking-related risks during pregnancy than self-reported smoking status. Future research should explore the relationship between urinary cotinine levels and other obstetric complications to validate its utility as a comprehensive pregnancy biomarker.
胎盘早剥是妊娠的一种严重并发症，吸烟是其众所周知的危险因素。然而，对吸烟影响的评估大多依赖于自我报告问卷，由于报告不准确和被动吸烟数据缺失，导致吸烟暴露情况呈现错误。可替宁是吸烟者体内主要的尼古丁代谢物和敏感生物标志物。然而，迄今为止，尚无关于尿可替宁水平与胎盘早剥发病之间关系的报道。因此，本研究旨在比较自我报告评估的吸烟状况和尿可替宁水平与胎盘早剥的关系。
我们分析了2011年1月至2014年3月期间在日本全国范围内开展的最大规模出生队列研究的数据。排除多胎妊娠和数据不足的女性，共有82637名女性符合研究条件。根据先前报道的尿可替宁水平可比临界值，参与者被分类为非吸烟者（<0.31μg/gCr）、被动吸烟者（0.31 - 36.7μg/gCr）或主动吸烟者（≥36.8μg/gCr）。参与者还根据自我报告问卷被分类为从不吸烟者、孕前戒烟者、孕后戒烟者或当前吸烟者。采用逻辑回归计算尿可替宁水平和自我报告吸烟状况与胎盘早剥关联的调整比值比（aORs）及95%置信区间（CIs）。
在82637名参与者（平均年龄：31.3岁）中，346名（0.42%）发生了胎盘早剥。基于尿可替宁评估的吸烟状况，主动吸烟者发生胎盘早剥的发生率（aOR，1.70；95%CI，1.20 - 2.40）高于非吸烟者。相比之下，基于自我报告，在调整既定混杂因素后，当前吸烟者与从不吸烟者之间无显著差异（aOR，1.54；95%CI，0.98 - 2.36）。
孕期尿可替宁水平升高与胎盘早剥风险增加显著相关，而自我报告的吸烟状况则不然。与自我报告的吸烟状况相比，尿可替宁水平是评估孕期吸烟相关风险更准确且临床更可靠的生物标志物。未来研究应探索尿可替宁水平与其他产科并发症之间的关系，以验证其作为综合妊娠生物标志物的效用。
