Preconception caffeine metabolites, caffeinated beverage intake, and fecundability

A C Perdue-Smithe et al, 2022.
American Journal of Clinical Nutrition
January 12, 2022

ABSTRACT

Background:

Caffeine is the most frequently used psychoactive substance in the U.S. and more than 90% of reproductive-age women report some level 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.

Objectives:

Our objective was to examine associations between preconception serum caffeine metabolites, caffeinated beverage intake, and fecundability.

Methods:

Participants included 1228 women aged 18-40 years with a history of 1-2 pregnancy losses in the Effects of Aspirin in Gestation and Reproduction (EAGeR) 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 and self-reported usual intake of baseline and time-varying cycle-average caffeinated beverages, with fecundability. Using Cox proportional hazards models, we estimated fecundability odds ratios (FOR) and 95% confidence intervals (CI) according to each metabolite. Follow-up was complete for 89% (n = 1088) of participants.

Results:

At baseline, 85%, 73%, and 91% of women had detectable serum caffeine, paraxanthine, and theobromine, respectively. 797 women became pregnant during ≤ 6 cycles of preconception follow-up. After adjusting for potential confounders, neither serum caffeine (Tertile (T)3 vs 1 FOR = 0.87; 95% CI = 0.71, 1.08), paraxanthine (T3 vs 1 FOR = 0.92; 95% CI = 0.75, 1.14), nor theobromine (T3 vs 1 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 vs 0 servings/d adjusted FOR = 0.99; 95% CI = 0.74, 1.34), nor was caffeinated coffee (>2 vs 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).

Conclusions:

Our findings are reassuring that caffeine exposure from usual low to moderate caffeinated beverage intake likely does not influence fecundability.

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