Maternal Caffeine Use And Pregnancy Outcome

母亲摄入咖啡因在不良妊娠结局发病机制中的作用存在争议。一些研究发现，与不使用咖啡因的女性相比，摄入咖啡因的女性发生自然流产和胎儿生长受限的风险增加。然而，其他同样做得很好的研究发现，咖啡因消费没有有害影响。此外，一些研究报告说，咖啡因只对吸烟的女性有害。以前所有关于这个问题的研究都依赖于母亲报告的咖啡因使用情况;没有研究使用咖啡因的生物标志物。该项目首先验证了使用血清咖啡因及其代谢物作为咖啡因摄入量的标志物，然后研究了这些血清标志物作为不良妊娠结局的危险因素。在验证研究中，血清副黄嘌呤被确定为咖啡因摄入量的可接受标志物。作为该项目的一部分，在大约450名妇女的血清中测定了尼古丁代谢产物可替宁的浓度，并将结果与她们报告的吸烟情况进行了比较。研究发现，女性在报告自己是否吸烟时非常诚实，但其血清可替宁浓度与吸烟量仅中度相关。这是两个相隔30年的独立女性群体的情况。在这个项目的主要部分，副黄嘌呤，咖啡因的主要代谢产物的血清浓度进行了比较，591名妇女经历了自然流产和2558名妇女与活产谁有血清提请在同一时间怀孕的妇女与自然损失。此外，在这2515名妇女中评估了胎儿生长迟缓与孕晚期副黄嘌呤血清浓度之间的关系。经历自然流产的女性中副黄嘌呤的平均浓度高于经历活产的女性（752 vs 583 ng/ml）。进一步的分析表明，这可能是由于少数妇女的副黄嘌呤浓度很高。血清副黄嘌呤浓度大于第95百分位数的比值比为1.86（p<0.01），但中间浓度与自然流产风险升高无关。这些结果表明，在怀孕期间适量摄入咖啡因不会增加自然流产的风险。在对照组中，2515名妇女提供了妊娠晚期血清样本。该样本中的平均副黄嘌呤浓度在随后生下小于胎龄（SGA）婴儿的妇女中（754 ng/ml）高于生下适当生长婴儿的妇女（654 ng/ml，p=0.03）。在非吸烟者中，副黄嘌呤与SGA分娩之间没有统计学显著相关性（p=0.48）。在吸烟者中，血清对羟基苯丙氨酸浓度增加与SGA出生风险增加相关（p=0.03）。在最近的一项研究中，对储存血清中副黄嘌呤的准确性和稳定性进行了研究。

The role of maternal caffeine consumption in the pathogenesis of adverse pregnancy outcomes is controversial. Several studies have found that women who consume caffeine are at increased risk of spontaneous abortion and fetal growth restriction compared to non-users. However, other equally well-done studies have found no harmful effects of caffeine consumption. In addition, several studies have reported that caffeine is harmful only among women who smoke. All previous studies of this question have relied on maternally-reported caffeine use; no studies have employed a biomarker for caffeine. This project first validated the use of serum caffeine and its metabolites as a marker for caffeine intake, and then studied these serum markers as a risk factor for adverse pregnancy outcome. In the validation study, serum paraxanthine was determined to be an acceptable marker for caffeine intake. As part of this project, the concentration of cotinine, a metabolite of nicotine, was assayed in the serum of approximately 450 of the women and the results compared to their reported cigarette smoking. Women were found to be very honest in reporting whether they smoked, but their serum concentration of cotinine correlated only moderately with the amount smoked. This was the case for two separate populations of women 30 years apart. In the main part of this project, the serum concentration of paraxanthine, caffeine's primary metabolite, was compared between 591 women experiencing a spontaneous abortion and 2558 women with live births who had serum drawn at the same time of pregnancy as the women with spontaneous loss. In addition, the association between reduced fetal growth and third-trimester paraxanthine serum concentrations was evaluated among these 2515 women. The mean concentration of paraxanthine was higher in women experiencing a spontaneous abortion than women experiencing a live birth (752 vs 583 ng/ml). Further analysis revealed that this may be explained by a few women with very high concentrations of paraxanthine. The odds ratio for serum paraxanthine concentration greater than the 95th percentile was 1.86 (p<0.01), but intermediate concentrations were not associated with an elevated risk of spontaneous abortion. These results suggest that moderate caffeine consumption during pregnancy does not increase the risk of spontaneous abortion. Among the control women, 2515 provided a third-trimester serum sample. The mean paraxanthine concentration in this sample was higher among women who subsequently gave birth to a small-for-gestational age (SGA) infant (754 ng/ml) than among women who gave birth to appropriately-grown infants (654 ng/ml, p=0.03). There was no statistically significant association between paraxanthine and SGA birth among non-smokers (p=0.48). Among smokers, increasing serum paraxhantine concentration was associated with an increased risk of SGA birth (p=0.03). In a recent publcation, the accuracy and stability of paraxanthine in stored serum was addressed.