Division of Women's Health, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
Am J Clin Nutr. 2022 Apr 1;115(4):1227-1236. doi: 10.1093/ajcn/nqab435.
Caffeine is the most frequently used psychoactive substance in the United States and >90% of reproductive-age women report some amount of intake daily. Despite biological plausibility, previous studies on caffeine and fecundability report conflicting results. Importantly, prior studies measured caffeine exposure exclusively by self-report, which is subject to measurement error and does not account for factors that influence caffeine metabolism.
Our objective was to examine associations between preconception serum caffeine metabolites, caffeinated beverage intake, and fecundability.
Participants included 1228 women aged 18-40 y with a history of 1-2 pregnancy losses in the EAGeR (Effects of Aspirin in Gestation and Reproduction) trial. We prospectively evaluated associations of preconception caffeine metabolites (i.e., caffeine, paraxanthine, and theobromine) measured from 1191 serum samples untimed to a specific time of day, self-reported usual caffeinated beverage intakes at baseline, and time-varying cycle-average caffeinated beverage intake, with fecundability. Using Cox proportional hazards models, we estimated fecundability odds ratios (FORs) and 95% CIs according to each metabolite. Follow-up was complete for 89% (n = 1088) of participants.
At baseline, 85%, 73%, and 91% of women had detectable serum caffeine, paraxanthine, and theobromine, respectively. A total of 797 women became pregnant during ≤6 cycles of preconception follow-up. After adjusting for potential confounders, neither serum caffeine [tertile (T)3 compared with T1 FOR: 0.87; 95% CI: 0.71, 1.08], paraxanthine (T3 compared with T1 FOR: 0.92; 95% CI: 0.75, 1.14), nor theobromine (T3 compared with T1 FOR: 1.15; 95% CI: 0.95, 1.40) were associated with fecundability. Baseline intake of total caffeinated beverages was not associated with fecundability (>3 compared with 0 servings/d adjusted FOR: 0.99; 95% CI: 0.74, 1.34), nor was caffeinated coffee (>2 compared with 0 servings/d adjusted FOR: 0.93; 95% CI: 0.45, 1.92) or caffeinated soda (>2 servings/d adjusted FOR: 0.92; 95% CI: 0.71, 1.20).
Our findings are reassuring that caffeine exposure from usual low to moderate caffeinated beverage intake likely does not influence fecundability.This trial was registered at clinicaltrials.gov as NCT00467363.
咖啡因是美国使用最广泛的精神活性物质，>90%的育龄期女性每天都有一定量的摄入。尽管有生物学上的合理性，但之前关于咖啡因和生育能力的研究结果却相互矛盾。重要的是，之前的研究仅通过自我报告来衡量咖啡因暴露情况，这容易受到测量误差的影响，并且没有考虑到影响咖啡因代谢的因素。
我们的目的是研究受孕前血清咖啡因代谢物、含咖啡因饮料的摄入与生育能力之间的关系。
参与者包括 1228 名年龄在 18-40 岁之间、在 EAGeR（阿司匹林在妊娠和生殖中的作用）试验中有 1-2 次妊娠失败史的女性。我们前瞻性地评估了受孕前从 1191 份未定时血清样本中测量的咖啡因代谢物（咖啡因、副黄嘌呤和可可碱）、基线时自我报告的常规含咖啡因饮料摄入量以及时变的周期平均含咖啡因饮料摄入量与生育能力之间的关系。我们使用 Cox 比例风险模型，根据每种代谢物估计生育能力比值比（FOR）和 95%置信区间。89%（n=1088）的参与者完成了随访。
在基线时，分别有 85%、73%和 91%的女性血清中可检测到咖啡因、副黄嘌呤和可可碱。共有 797 名女性在≤6 个周期的受孕前随访期间怀孕。在调整了潜在混杂因素后，血清咖啡因（T3 与 T1 FOR：0.87；95%CI：0.71，1.08）、副黄嘌呤（T3 与 T1 FOR：0.92；95%CI：0.75，1.14）和可可碱（T3 与 T1 FOR：1.15；95%CI：0.95，1.40）均与生育能力无关。总含咖啡因饮料的基线摄入量与生育能力无关（>3 份与 0 份/天调整后的 FOR：0.99；95%CI：0.74，1.34），也与含咖啡因咖啡（>2 份与 0 份/天调整后的 FOR：0.93；95%CI：0.45，1.92）或含咖啡因苏打水（>2 份/天调整后的 FOR：0.92；95%CI：0.71，1.20）无关。
我们的研究结果令人安心，即从通常的低到中等量的含咖啡因饮料摄入中摄入咖啡因不太可能影响生育能力。这项试验在 clinicaltrials.gov 上注册为 NCT00467363。
