BACKGROUND Coffee consumption has been associated with several adverse pregnancy outcomes, although data from randomized-controlled trials are lacking. We investigate whether there is a causal relationship between coffee consumption and miscarriage, stillbirth, birthweight, gestational age and pre-term birth using Mendelian randomization (MR). METHODS A two-sample MR study was performed using summary results data from a genome-wide association meta-analysis of coffee consumption (N = 91 462) from the Coffee and Caffeine Genetics Consortium. Outcomes included self-reported miscarriage (N = 49 996 cases and 174 109 controls from a large meta-analysis); the number of stillbirths [N = 60 453 from UK Biobank (UKBB)]; gestational age and pre-term birth (N = 43 568 from the 23andMe, Inc cohort) and birthweight (N = 297 356 reporting own birthweight and N = 210 248 reporting offspring's birthweight from UKBB and the Early Growth Genetics Consortium). Additionally, a one-sample genetic risk score (GRS) analysis of coffee consumption in UKBB women (N up to 194 196) and the Avon Longitudinal Study of Parents and Children (N up to 6845 mothers and 4510 children) and its relationship with offspring outcomes was performed. RESULTS Both the two-sample MR and one-sample GRS analyses showed no change in risk of sporadic miscarriages, stillbirths, pre-term birth or effect on gestational age connected to coffee consumption. Although both analyses showed an association between increased coffee consumption and higher birthweight, the magnitude of the effect was inconsistent. CONCLUSION Our results suggest that coffee consumption during pregnancy might not itself contribute to adverse outcomes such as stillbirth, sporadic miscarriages and pre-term birth or lower gestational age or birthweight of the offspring.

中文翻译：

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母亲喝咖啡的孟德尔随机研究及其对出生体重、死产、流产、胎龄和早产的影响。

背景 尽管缺乏来自随机对照试验的数据，但喝咖啡与几种不良妊娠结局有关。我们使用孟德尔随机化 (MR) 调查咖啡消费与流产、死产、出生体重、胎龄和早产之间是否存在因果关系。方法 使用来自咖啡和咖啡因遗传学联合会的咖啡消费全基因组关联荟萃分析 (N = 91 462) 的汇总结果数据，进行了双样本 MR 研究。结果包括自我报告的流产（N = 49 996 个病例和来自大型荟萃分析的 174 109 个对照）；死产数量 [N = 60 453 来自英国生物银行 (UKBB)]；胎龄和早产（N = 43 568 来自 23andMe，Inc 队列）和出生体重（N = 297 356 报告自己的出生体重，N = 210 248 从 UKBB 和 Early Growth Genetics Consortium 报告后代的出生体重）。此外，UKBB 女性咖啡消费量的单样本遗传风险评分 (GRS) 分析（N 高达 194196）和雅芳父母和儿童纵向研究（N 高达 6845 名母亲和 4510 名儿童）及其与后代的关系结果进行了。结果 双样本 MR 和单样本 GRS 分析均显示，与咖啡消费相关的偶发性流产、死产、早产或对胎龄影响的风险没有变化。尽管两项分析都表明咖啡摄入量增加与出生体重增加之间存在关联，但影响的大小并不一致。