BACKGROUND In pregnancy, women are encouraged to cease smoking and limit caffeine intake. We employed objective definitions of smoking and caffeine exposure to assess their association with adverse outcomes. METHODS We conducted a case cohort study within the Pregnancy Outcome Prediction study to analyse maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age. Objective smoking status was defined based on detectable cotinine levels at each time point and objective caffeine exposure was based on tertiles of paraxanthine levels at each time point. We used logistic and linear regression to examine the association between cotinine, paraxanthine and the risk of pre-eclampsia, spontaneous pre-term birth (sPTB), fetal growth restriction (FGR), gestational diabetes mellitus and birthweight. RESULTS There were 914 and 915 women in the smoking and caffeine analyses, respectively. Compared with no exposure to smoking, consistent exposure to smoking was associated with an increased risk of sPTB [adjusted odds ratio (aOR) = 2.58, 95% CI: 1.14 to 5.85)] and FGR (aOR = 4.07, 95% CI: 2.14 to 7.74) and lower birthweight (β = -387 g, 95% CI: -622 g to -153 g). On univariate analysis, consistently high levels of paraxanthine were associated with an increased risk of FGR but that association attenuated when adjusting for maternal characteristics and objective-but not self-reported-smoking status. CONCLUSIONS Based on objective data, consistent exposure to smoking throughout pregnancy was strongly associated with sPTB and FGR. High levels of paraxanthine were not independently associated with any of the studied outcomes and were confounded by smoking.

中文翻译：

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客观测量吸烟和咖啡因摄入量以及不良妊娠结局的风险。

背景技术在怀孕期间，鼓励妇女戒烟并限制咖啡因的摄入量。我们采用吸烟和咖啡因暴露的客观定义来评估它们与不良后果的关联。方法 我们在妊娠结果预测研究中进行了一项病例队列研究，以分析孕龄 12、20、28 和 36 周样本中的母体血清代谢组学。客观吸烟状况是根据每个时间点可检测到的可替宁水平来定义的，客观咖啡因暴露是根据每个时间点的副黄嘌呤水平的三分位数来定义的。我们使用逻辑回归和线性回归来检查可替宁、副黄嘌呤与先兆子痫、自发性早产（sPTB）、胎儿生长受限（FGR）、妊娠糖尿病和出生体重的风险之间的关联。结果 分别有 914 名女性和 915 名女性参与了吸烟和咖啡因分析。与不吸烟相比，持续吸烟与 sPTB [调整后比值比 (aOR) = 2.58，95% CI：1.14 至 5.85)] 和 FGR (aOR = 4.07，95% CI：2.14) 风险增加相关。至 7.74）和较低的出生体重（β = -387 g，95% CI：-622 g 至 -153 g）。在单变量分析中，持续高水平的副黄嘌呤与 FGR 风险增加相关，但在调整母亲特征和客观而非自我报告的吸烟状况后，这种关联减弱。结论 根据客观数据，整个怀孕期间持续吸烟与 sPTB 和 FGR 密切相关。高水平的副黄嘌呤与任何研究结果均不独立相关，并且与吸烟混淆。